Trial Outcomes & Findings for Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma (NCT NCT00782275)

NCT ID: NCT00782275

Last Updated: 2018-01-24

Results Overview

4-month progression-free survival rate was defined as the percentage of participants absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 41 participants
• Primary outcome timeframe: Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment. Relevant for this endpoint was disease status at 4 months.
• Results posted on: 2018-01-24

Participant Flow

Participants were enrolled between April 2009 and May 2013.

Participant milestones

Measure	Bevacizumab + Temsirolimus bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.
Overall Study STARTED	41
Overall Study Treated	40
Overall Study Prior VEGFR Response Evaluable	39
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	41

Reasons for withdrawal

Measure	Bevacizumab + Temsirolimus bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.
Overall Study Adverse Event	11
Overall Study Withdrawal by Subject	1
Overall Study Progressive Disease	21
Overall Study Physician Decision	4
Overall Study Not started treatment	1
Overall Study Other	3

Baseline Characteristics

One patient did not have enough data to determine VEGF-refractory status.

Baseline characteristics by cohort

Measure	Bevacizumab + Temsirolimus n=40 Participants bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants
Region of Enrollment United States	40 Participants n=5 Participants
Primary VEGF Refractory Status VEGF Refractory-No	20 Participants n=5 Participants • One patient did not have enough data to determine VEGF-refractory status.
Primary VEGF Refractory Status VEGF Refractory-Yes	19 Participants n=5 Participants • One patient did not have enough data to determine VEGF-refractory status.
Primary VEGF Refractory Status Unevaluable	1 Participants n=5 Participants • One patient did not have enough data to determine VEGF-refractory status.
MSKCC Risk Category Favorable	5 Participants n=5 Participants
MSKCC Risk Category Intermediate	31 Participants n=5 Participants
MSKCC Risk Category Poor	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment. Relevant for this endpoint was disease status at 4 months.

Population: The analysis dataset is comprised of all treated participants.

4-month progression-free survival rate was defined as the percentage of participants absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Outcome measures

Measure

Bevacizumab + Temsirolimus n=40 Participants bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.

4-month Progression-Free Survival Rate

65 percentage of participants Interval 50.8 to 77.5

SECONDARY outcome

Timeframe: Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment; Treatment continued until disease progression or unacceptable toxicity. Median (range) of treatment duration for this study cohort was 5 cycles (1-39) [1 cycle=28days].

Population: The analysis dataset is comprised of all treated participants.

Objective response (OR) rate is the percentage of participants achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Outcome measures

Measure

Bevacizumab + Temsirolimus n=40 Participants bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.

Objective Response Rate

17.5 percentage of participants Interval 8.5 to 30.4

SECONDARY outcome

Timeframe: Median follow-up for survival in this study cohort is 56 months.

Population: The analysis dataset is comprised of all treated participants.

Overall survival (OS) is defined from the date of registration to date of death, or censored at the date the participant was last known alive. OS is estimated based on the Kaplan-Meier method.

Outcome measures

Measure

Bevacizumab + Temsirolimus n=40 Participants bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.

Overall Survival

12.2 months Interval 7.7 to 21.9

Adverse Events

Bevacizumab + Temsirolimus

Serious events: 28 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab + Temsirolimus n=40 participants at risk bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.
Blood and lymphatic system disorders Hemoglobin	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Cardiac disorders Ventricular arrhythmia NOS	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Enteritis	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Fistula, Esophageal	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Nausea	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Vomiting	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Lower GI, hemorrhage NOS	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Fatigue	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Fever w/o neutropenia	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Edema limb	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Syndromes-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Infections and infestations Infection w/ unk ANC skin (cellulitis)	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Infections and infestations Infection w/ unk ANC blood	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Injury, poisoning and procedural complications Wound - non-infectious	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Injury, poisoning and procedural complications Vascular access,Thrombosis/embolism	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Haptoglobin	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Neutrophils	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Weight gain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations PTT	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Alkaline phosphatase	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations ALT, SGPT	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations AST, SGOT	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Hypercholesterolemia	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Anorexia	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Dehydration	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hyponatremia	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypertriglyceridemia	15.0% 6/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Neck, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Dizziness	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Syncope	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Head/headache	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Renal and urinary disorders Glomerular filtration rate	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Renal and urinary disorders Proteinuria	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Rash/desquamation	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Hypertension	12.5% 5/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Hypotension	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Thrombosis/thrombus/embolism	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pulmonary/ Upper Respiratory- other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Rash/ desquamation	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Thrombosis/ thrombus/ embolism	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.

Other adverse events

Measure	Bevacizumab + Temsirolimus n=40 participants at risk bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28 days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.
Blood and lymphatic system disorders Hemorrhage-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Blood and lymphatic system disorders Hemoglobinuria	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hyperuricemia	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Blood and lymphatic system disorders Hemoglobin	32.5% 13/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Blood and lymphatic system disorders Hematologic-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Cardiac disorders Palpitations	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Cardiac disorders Arrhythmia-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Cardiac disorders Cardiac-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Eye disorders Tearing	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Eye disorders Ocular-other	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Eye disorders Eye, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Chelitis	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Colitis	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Constipation	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Periodontal disease	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Diarrhea w/o prior colostomy	25.0% 10/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Distention/bloating, abdominal	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Dry mouth	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Dysphagia	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Dyspepsia	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Hemorrhoids	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	25.0% 10/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	32.5% 13/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Nausea	32.5% 13/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Vomiting	20.0% 8/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders GI-other	20.0% 8/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Oral cavity, hemorrhage	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Rectum, hemorrhage	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Abdomen, pain	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Anus, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Dental/teeth/peridontal, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Oral cavity, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Gastrointestinal disorders Oral gums, pain	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Fatigue	50.0% 20/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Fever w/o neutropenia	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Rigors/chills	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Constitutional, other	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Edema head and neck	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Edema limb	17.5% 7/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Edema trunk/genital	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Chest/thoracic pain NOS	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Face, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
General disorders Pain-other	12.5% 5/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Immune system disorders Allergy-other	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Infections and infestations Infection Gr0-2 neut, sinus	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Infections and infestations Infection Gr0-2 neut, skin	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Infections and infestations Infection w/ unk ANC nerve-peripheral	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Infections and infestations Infection-other	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Injury, poisoning and procedural complications Bruising	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Leukocytes	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Lymphopenia	12.5% 5/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Platelets	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Weight gain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Weight loss	30.0% 12/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations INR	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations PTT	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Alkaline phosphatase	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations ALT, SGPT	15.0% 6/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations AST, SGOT	17.5% 7/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Hypercholesterolemia	37.5% 15/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Creatinine	27.5% 11/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Investigations Metabolic/Laboratory-other	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Anorexia	35.0% 14/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Dehydration	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypoalbuminemia	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypocalcemia	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	17.5% 7/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hyperkalemia	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypokalemia	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hyponatremia	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Metabolism and nutrition disorders Hypertriglyceridemia	35.0% 14/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	7.5% 3/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Musculoskeletal/soft tissue-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Back, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Chest wall, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Extremity-limb, pain	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Joint, pain	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Musculoskeletal and connective tissue disorders Muscle, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Taste disturbance	15.0% 6/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Dizziness	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Neuropathy-motor	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Neuropathy-sensory	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Neurologic-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Head/headache	25.0% 10/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Nervous system disorders Sinus, pain	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Psychiatric disorders Insomnia	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Renal and urinary disorders Urinary hemorrhage NOS	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Renal and urinary disorders Glomerular filtration rate	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Renal and urinary disorders Proteinuria	30.0% 12/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Renal and urinary disorders Renal/GU-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Reproductive system and breast disorders Erectile impotence	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Muco/stomatitis (symptom) larynx	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Muco/stomatitis (symptom) pharynx	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	37.5% 15/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pleura, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Throat/pharynx/larynx, pain	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	22.5% 9/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	20.0% 8/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reaction	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	22.5% 9/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	17.5% 7/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-other	22.5% 9/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Sweating	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	20.0% 8/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Hyperpigmentation	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Nail changes	5.0% 2/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Pruritus/itching	30.0% 12/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Rash/desquamation	22.5% 9/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	30.0% 12/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Hand-foot reaction	15.0% 6/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Skin breakdown/decubitus ulcer	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Skin-other	17.5% 7/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Skin and subcutaneous tissue disorders Scalp, pain	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Hypertension	10.0% 4/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Hypotension	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Flushing	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Hemorrhage-other	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.
Vascular disorders Phlebitis	2.5% 1/40 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 5 (1-39) which parallels time in months given the 28 day cycle duration. Maximum grade toxicity by type was first calculated including events only with temsirolimus and/or bevacizumab treatment-attribution of possibly, probably or definitely. Serious AEs were defined as grade 3 or higher events per CTCAEv3. Other AEs were defined as grades 1 or 2 events per CTCAEv3. No further data is available to specify classification of 'other' beyond the general term.

Additional Information

David F. McDermott MD PhD

Beth Israel Deaconess Medical Center

Phone: 617-632-9262

Email: dmcdermo@bidmc.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place