Trial Outcomes & Findings for Palbociclib With Everolimus + Exemestane In BC (NCT NCT02871791)

Last Updated: 2022-08-29

Results Overview

CBR is defined as the proportion of participants achieving complete response, partial response or stable disease for more than 6 months (CR+PR+SD ≥ 24 weeks) taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.

Results posted on

2022-08-29

Participant Flow

September 12, 2016 to June 26, 2019

Participant milestones

Participant milestones
Measure	Dose 0: Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	Dose 1: Palbociclib 125mg, Everolimus 5mg, Exemestane 25mg * Palbociclib 125mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Phase 1b STARTED	6	3
Phase 1b COMPLETED	0	0
Phase 1b NOT COMPLETED	6	3
Phase 2 STARTED	32	0
Phase 2 COMPLETED	29	0
Phase 2 NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose 0: Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	Dose 1: Palbociclib 125mg, Everolimus 5mg, Exemestane 25mg * Palbociclib 125mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Phase 1b Death	0	1
Phase 1b progressive disease	6	2
Phase 2 Death	1	0
Phase 2 Lost to Follow-up	2	0

Baseline Characteristics

Palbociclib With Everolimus + Exemestane In BC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	[Phase 2a] Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg n=32 Participants * Palbociclib 100 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	[Phase 1b]Dose 0: Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg n=6 Participants * Palbociclib 100 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	[Phase 1b]Dose 1: Palbociclib 125mg, Everolimus 5mg, Exemestane 25mg n=3 Participants * Palbociclib 125 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	Total n=41 Participants Total of all reporting groups
Age, Continuous	55.5 years n=5 Participants	52 years n=7 Participants	68 years n=5 Participants	55.5 years n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	41 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	29 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	38 Participants n=4 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	32 participants n=5 Participants	6 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants

PRIMARY outcome

Timeframe: Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.

Outcome measures

Outcome measures
Measure	Palbociclib, Everolimus, Exemestane n=32 Participants * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Clinical Benefit Rate (CBR) [Phase 2a]	6 Participants

SECONDARY outcome

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.

Outcome measures

Outcome measures
Measure	Palbociclib, Everolimus, Exemestane n=32 Participants * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Overall Response Rate (ORR) [Phase 2a]	0 Participants

SECONDARY outcome

Population: 2 patients lost follow-up from the study after treatment begins

The DCR defined as the proportion of patient that has CR+PR+SD\>=12 weeks. Response will be assessed among participants eligible for the phase IIa part of the study who received at least one dose of the study drugs at the MTD/RP2D and have measurable disease at screening.

Outcome measures

Outcome measures
Measure	Palbociclib, Everolimus, Exemestane n=30 Participants * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Disease Control Rate (DCR) [Phase 2a]	0.563 proportion of patients Interval 0.393 to 0.719

SECONDARY outcome

Response will be assessed among participants eligible for the phase IIa part of the study who received at least one dose of the study drugs at the MTD/RP2D and have measurable disease at screening. DOR defined based on the duration of stable disease.

Outcome measures

Outcome measures
Measure	Palbociclib, Everolimus, Exemestane n=32 Participants * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Duration of Response (DOR) [Phase 2a]	4.24 months Interval 3.68 to 7.82

SECONDARY outcome

Timeframe: Disease is evaluated and followed-up every 8 weeks, with median of 20.04 months and maximum of 35.64 months.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 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

Outcome measures
Measure	Palbociclib, Everolimus, Exemestane n=32 Participants * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Median Progression Free Survival (PFS) [Phase 2a]	3.8 months Interval 2.0 to 5.4

Adverse Events

[Phase 2a] Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg

Serious events: 28 serious events

Other events: 32 other events

Deaths: 16 deaths

[Phase 1b]Dose 0: Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

[Phase 1b]Dose 1: Palbociclib 125mg, Everolimus 5mg, Exemestane 25mg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Sara Tolaney, MD MPH

Dana-Farber Cancer Institute

Phone: 617-632-5743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	[Phase 2a] Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg n=32 participants at risk * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	[Phase 1b]Dose 0: Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg n=6 participants at risk * Palbociclib 100 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	[Phase 1b]Dose 1: Palbociclib 125mg, Everolimus 5mg, Exemestane 25mg n=3 participants at risk * Palbociclib 125 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Investigations Alanine aminotransferase increased	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Anemia	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	12.5% 4/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastric ulcer	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	15.6% 5/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	78.1% 25/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	66.7% 4/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	100.0% 3/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Pain in extremity	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	9.4% 3/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.

Other adverse events
Measure	[Phase 2a] Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg n=32 participants at risk * Palbociclib 100mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	[Phase 1b]Dose 0: Palbociclib 100mg, Everolimus 5mg, Exemestane 25mg n=6 participants at risk * Palbociclib 100 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule	[Phase 1b]Dose 1: Palbociclib 125mg, Everolimus 5mg, Exemestane 25mg n=3 participants at risk * Palbociclib 125 mg will be administered orally, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus 5 mg will be administered orally, once daily on a 28 day schedule * Exemestane 25 mg will be administered orally, once daily on a 28 day schedule
Gastrointestinal disorders Flatulence	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal pain	12.5% 4/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	21.9% 7/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	9.4% 3/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Immune system disorders Allergic reaction	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	9.4% 3/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 2/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Anemia	6.2% 2/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	25.0% 8/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthralgia	9.4% 3/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	15.6% 5/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Back pain	6.2% 2/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Blood bilirubin increased	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Brachial plexopathy	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Breast pain	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Chills	6.2% 2/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	9.4% 3/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 4/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Investigations Creatinine increased	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	12.5% 4/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Depression	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 2/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	31.2% 10/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dry mouth	12.5% 4/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	6.2% 2/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dysgeusia	21.9% 7/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dyspepsia	6.2% 2/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	18.8% 6/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 2/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Edema limbs	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Endocrine disorders Endocrine disorders - Other, specify	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Enterocolitis	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Epistaxis	18.8% 6/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	65.6% 21/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	50.0% 3/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	66.7% 2/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Fever	9.4% 3/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
General disorders Gait disturbance	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	25.0% 8/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 2/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Hemorrhoids	0.00% 0/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	33.3% 1/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Hiccups	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hot flashes	3.1% 1/32 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	16.7% 1/6 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.	0.00% 0/3 • Adverse events are evaluated every 8 days each cycle on treatment, and at the end of the therapy. Treatment duration has a median of 111 days and maximum of 681 days. Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.