Trial Outcomes & Findings for Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer (NCT NCT00232505)

Last Updated: 2017-06-28

Results Overview

Overall response rate of single agent cetuximab and cetuximab + carboplatin will be measured by radiographic response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria every 8 weeks until subject experiences disease progression. Overall response will be measured as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD).Per RECIST v1.0 for target lesions and assessed by CT (spiral): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

112 participants

Primary outcome timeframe

5 years

Results posted on

2017-06-28

Participant Flow

Subjects were recruited between December 2005 and October 2007 from thirteen cancer centers throughout the US.

Four patients declined participation for personal reasons, three were screen failures, three had death or progression during the screening period.

Participant milestones

Participant milestones
Measure	Cetuximab Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
Overall Study STARTED	31	71
Overall Study Not Evaluable	0	6
Overall Study Early Progressors	2	5
Overall Study Off Protocol	5	0
Overall Study COMPLETED	26	60
Overall Study NOT COMPLETED	5	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cetuximab n=31 Participants Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin n=71 Participants Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV	Total n=102 Participants Total of all reporting groups
Age, Continuous	49 years n=5 Participants	52 years n=7 Participants	50.5 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	71 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	51 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	71 participants n=7 Participants	102 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	17 Participants n=5 Participants	37 Participants n=7 Participants	54 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	14 Participants n=5 Participants	28 Participants n=7 Participants	42 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status missing	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Menopausal Status Postmenopausal	21 Participants n=5 Participants	56 Participants n=7 Participants	77 Participants n=5 Participants
Menopausal Status Pre- or perimenopausal	10 Participants n=5 Participants	15 Participants n=7 Participants	25 Participants n=5 Participants
Dominant metastatic site Lung	9 Participants n=5 Participants	20 Participants n=7 Participants	29 Participants n=5 Participants
Dominant metastatic site Liver	8 Participants n=5 Participants	17 Participants n=7 Participants	25 Participants n=5 Participants
Dominant metastatic site Lymph nodes	4 Participants n=5 Participants	14 Participants n=7 Participants	18 Participants n=5 Participants
Dominant metastatic site Locoregional	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Dominant metastatic site Bone	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Dominant metastatic site Skin/soft tissue	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Dominant metastatic site Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Treatment Prior chemotherapy	30 participants n=5 Participants	67 participants n=7 Participants	97 participants n=5 Participants
Treatment Adjuvant/neoadjuvant	26 participants n=5 Participants	60 participants n=7 Participants	86 participants n=5 Participants
Treatment Metastatic	21 participants n=5 Participants	34 participants n=7 Participants	55 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years

Outcome measures

Outcome measures
Measure	Cetuximab n=31 Participants Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin After Cetuximab Alone n=25 Participants Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin	Cetuximab and Carboplatin n=71 Participants Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV	Cetuximab and Carboplatin Subset n=51 Participants patients receiving cetuximab and carboplatin who had confirmed basal-like disease by quantitative realtime polymerase chain reaction-based intrinsic subtype assay
Overall Disease Response Rate Complete response	0 Participants	0 Participants	1 Participants	1 Participants
Overall Disease Response Rate Partial response	2 Participants	4 Participants	11 Participants	17 Participants
Overall Disease Response Rate Stable disease	3 Participants	7 Participants	15 Participants	8 Participants
Overall Disease Response Rate Stable disease > 6 months	1 Participants	3 Participants	10 Participants	7 Participants
Overall Disease Response Rate Progressive disease	26 Participants	12 Participants	38 Participants	32 Participants
Overall Disease Response Rate Not evaluable	0 Participants	2 Participants	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Every four months until death of any cause or end of data collection up to 40 months

Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.

Outcome measures

Outcome measures
Measure	Cetuximab n=31 Participants Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin After Cetuximab Alone n=71 Participants Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin	Cetuximab and Carboplatin Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV	Cetuximab and Carboplatin Subset patients receiving cetuximab and carboplatin who had confirmed basal-like disease by quantitative realtime polymerase chain reaction-based intrinsic subtype assay
Overall Survival Baseline	31 participants surviving	71 participants surviving	—	—
Overall Survival 4 months	22 participants surviving	56 participants surviving	—	—
Overall Survival 8 months	12 participants surviving	41 participants surviving	—	—
Overall Survival 12 months	9 participants surviving	30 participants surviving	—	—
Overall Survival 16 months	8 participants surviving	23 participants surviving	—	—
Overall Survival 20 months	8 participants surviving	19 participants surviving	—	—
Overall Survival 24 months	6 participants surviving	8 participants surviving	—	—
Overall Survival 28 months	5 participants surviving	4 participants surviving	—	—
Overall Survival 32 months	1 participants surviving	3 participants surviving	—	—
Overall Survival 36 months	1 participants surviving	2 participants surviving	—	—
Overall Survival 40 months	0 participants surviving	0 participants surviving	—	—

SECONDARY outcome

Timeframe: Every four months until progression, death of any cause, or end of data collection up to 40 months

Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment

Outcome measures

Outcome measures
Measure	Cetuximab n=31 Participants Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin After Cetuximab Alone n=71 Participants Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin	Cetuximab and Carboplatin Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV	Cetuximab and Carboplatin Subset patients receiving cetuximab and carboplatin who had confirmed basal-like disease by quantitative realtime polymerase chain reaction-based intrinsic subtype assay
Progression-Free Survival Baseline	31 participants	71 participants	—	—
Progression-Free Survival 4 months	4 participants	27 participants	—	—
Progression-Free Survival 8 months	2 participants	11 participants	—	—
Progression-Free Survival 12 months	2 participants	7 participants	—	—
Progression-Free Survival 16 months	1 participants	7 participants	—	—
Progression-Free Survival 20 months	1 participants	6 participants	—	—
Progression-Free Survival 24 months	1 participants	6 participants	—	—
Progression-Free Survival 28 months	1 participants	1 participants	—	—
Progression-Free Survival 32 months	1 participants	1 participants	—	—
Progression-Free Survival 36 months	1 participants	1 participants	—	—
Progression-Free Survival 40 months	0 participants	0 participants	—	—

Adverse Events

Cetuximab

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Cetuximab and Carboplatin After Cetuximab Alone

Serious events: 8 serious events

Other events: 24 other events

Deaths: 0 deaths

Cetuximab and Carboplatin

Serious events: 20 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Robin V. Johnson

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-1125

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Cetuximab n=31 participants at risk Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin After Cetuximab Alone n=25 participants at risk Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin	Cetuximab and Carboplatin n=71 participants at risk Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
Blood and lymphatic system disorders Edema: limb	6.5% 2/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	12.0% 3/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Anorexia	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Cardiac disorders Cardiac General - Other (Specify, __)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Psychiatric disorders Confusion	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Dehydration	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Diarrhea	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	9.9% 7/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Extremity-lower (gait/walking)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Fatigue (asthenia, lethargy, malaise)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Vascular disorders Flushing	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Gastrointestinal - Other (Specify, __)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Nervous system disorders Hemorrhage, CNS	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Hemorrhage, GI - Esophagus	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Vascular disorders Hypotension	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Cardiac disorders Left ventricular diastolic dysfunction	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Right-sided	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	6.5% 2/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Nausea	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Pain - Abdomen NOS	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Musculoskeletal and connective tissue disorders Pain - Bone	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Musculoskeletal and connective tissue disorders Pain - Chest wall	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Pain - Chest/thorax NOS	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Musculoskeletal and connective tissue disorders Pain - Extremity-limb	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Ear and labyrinth disorders Pain - Middle ear	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Pain - Other (Specify, __)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pain - Tumor pain	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.2% 3/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other (Specify, __)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy - possibly related to cancer treatment (Specify, __)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Nervous system disorders Seizure	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes

Other adverse events
Measure	Cetuximab n=31 participants at risk Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Cetuximab and Carboplatin After Cetuximab Alone n=25 participants at risk Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin	Cetuximab and Carboplatin n=71 participants at risk Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.2% 3/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Investigations Alkaline phosphatase	19.4% 6/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	24.0% 6/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	12.7% 9/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	7.0% 5/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	7.0% 5/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	7.0% 5/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Anorexia	19.4% 6/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	23.9% 17/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Musculoskeletal and connective tissue disorders Arthritis (non-septic)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Investigations AST, SGOT(serum glutamic oxaloacetic transaminase)	6.5% 2/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	16.0% 4/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.5% 6/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Reproductive system and breast disorders Breast function/lactation	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Injury, poisoning and procedural complications Bruising (in absence of Grade 3 or 4 thrombocytopenia)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	5.6% 4/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Cardiac disorders Cardiac General - Other (Specify, __)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Constipation	9.7% 3/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	16.0% 4/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	39.4% 28/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Constitutional Symptoms - Other (Specify, __)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.5% 6/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Cough	9.7% 3/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	12.0% 3/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	29.6% 21/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Creatinine	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Renal and urinary disorders Cystitis	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.2% 3/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Dehydration	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Specify, __)	12.9% 4/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	22.5% 16/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Diarrhea	19.4% 6/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	25.4% 18/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Nervous system disorders Dizziness	12.9% 4/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	12.7% 9/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Eye disorders Dry eye syndrome	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Skin and subcutaneous tissue disorders Dry skin	22.6% 7/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	16.0% 4/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	25.4% 18/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Dysphagia (difficulty swallowing)	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	9.7% 3/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	24.0% 6/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	32.4% 23/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Blood and lymphatic system disorders Edema: limb	16.1% 5/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	12.7% 9/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Extremity-lower (gait/walking)	6.5% 2/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Fatigue (asthenia, lethargy, malaise)	45.2% 14/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	56.0% 14/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	63.4% 45/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	9.7% 3/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.2% 3/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Vascular disorders Flushing	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Injury, poisoning and procedural complications Fracture	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	1.4% 1/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Gastrointestinal - Other (Specify, __)	9.7% 3/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.2% 3/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	3.2% 1/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	7.0% 5/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	6.5% 2/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	9.9% 7/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Gastrointestinal disorders Heartburn/dyspepsia	9.7% 3/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	11.3% 8/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Blood and lymphatic system disorders Hemoglobin	6.5% 2/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	8.0% 2/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	18.3% 13/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory - Nose	0.00% 0/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	0.00% 0/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	2.8% 2/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Vascular disorders Hot flashes/flushes	19.4% 6/31 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	4.0% 1/25 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes	16.9% 12/71 • Adverse events were collected up to 30 days after treatment Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes