Trial Outcomes & Findings for A Study of Pertuzumab With Erlotinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (NCT NCT02507375)

NCT ID: NCT02507375

Last Updated: 2015-10-16

Results Overview

A DLT was defined as: Any non-hematological toxicity ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events, version 3.0, except for fever, chills, and flu-like symptoms, which occurred despite adequate participant management. The following Grade 1-3 toxicities were exempt: Grade 1-3 skin and/or epithelial toxicities consistent with erlotinib single agent therapy, unless they did not respond to treatment or dose reduction or interruption (Grade 4 skin and/or epithelial toxicities were considered to be a DLT); Grade 4 neutropenia occurring for \> 7 days; febrile neutropenia which occurred despite adequate participant management; Grade 4 thrombocytopenia or any thrombocytopenia requiring platelet transfusion; and any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 17 participants
• Primary outcome timeframe: From baseline to end of the study (up to 42 weeks)
• Results posted on: 2015-10-16

Participant Flow

Seventeen patients enrolled in 3 centers. Three patients from cohort 1 and 1 patient from cohort 2 completed the 6 cycles of study therapy, as planned.

Two participants in cohort 2 did not begin experimental study drug treatment in Cycle 1, so were not included in the analysis set.The resulting participant flow includes only participants who received pertuzumab.

Participant milestones

Measure	Erlotinib 100 mg + Pertuzumab 420 mg Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Overall Study STARTED	6	9
Overall Study Cycle 1	6	9
Overall Study Received Pertuzumab	6	6
Overall Study Cycle 2	5	5
Overall Study Cycle 3	4	5
Overall Study Cycle 4	4	2
Overall Study Cycle 5	3	1
Overall Study Cycle 6	3	1
Overall Study Extension Period	2	1
Overall Study COMPLETED	2	1
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Measure	Erlotinib 100 mg + Pertuzumab 420 mg Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Overall Study Progressive Disease	4	5
Overall Study Death	0	1
Overall Study Refused treatment	0	1
Overall Study Adverse Event	0	1

Baseline Characteristics

A Study of Pertuzumab With Erlotinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=6 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg n=9 Participants Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Total n=15 Participants Total of all reporting groups
Age, Continuous	66.5 years STANDARD_DEVIATION 5.89 • n=5 Participants	56.0 years STANDARD_DEVIATION 10.28 • n=7 Participants	60.2 years STANDARD_DEVIATION 10.06 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Spain	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to end of the study (up to 42 weeks)

A DLT was defined as: Any non-hematological toxicity ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events, version 3.0, except for fever, chills, and flu-like symptoms, which occurred despite adequate participant management. The following Grade 1-3 toxicities were exempt: Grade 1-3 skin and/or epithelial toxicities consistent with erlotinib single agent therapy, unless they did not respond to treatment or dose reduction or interruption (Grade 4 skin and/or epithelial toxicities were considered to be a DLT); Grade 4 neutropenia occurring for > 7 days; febrile neutropenia which occurred despite adequate participant management; Grade 4 thrombocytopenia or any thrombocytopenia requiring platelet transfusion; and any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=6 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg n=6 Participants Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Percentage of Participants With Dose Limiting Toxicities (DLTs)	0 Percentage of participants	0 Percentage of participants	—

SECONDARY outcome

Timeframe: within 18 weeks

Population: Full analysis set

Responders are participants who achieved either a complete response or a partial response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=15 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg n=6 Participants Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg n=9 Participants Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Percentage of Participants Classified as Responders	20 percentage of participants	33.3 percentage of participants	11.1 percentage of participants

SECONDARY outcome

Timeframe: From baseline to the end of the study (up to 42 weeks)

Complete and partial responses were determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A complete response was defined as the disappearance of all target and non-target lesions. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=6 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg n=9 Participants Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6 Cycle 3	0 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6 Cycle 1	0 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6 Cycle 2	33.3 Percentage of participants	11.1 Percentage of participants	—
Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6 Cycle 4	33.3 Percentage of participants	11.1 Percentage of participants	—
Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6 Cycle 6	16.7 Percentage of participants	11.1 Percentage of participants	—

SECONDARY outcome

Timeframe: on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion

Population: Pharmacokinetic analysis subset, defined as all participants from either cohort with adequate data for performing PK analysis

Maximum Observed Plasma Concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered, typically measured in nanograms/milliliter (ng/mL), reported as mg/L.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=8 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Peak Plasma Concentration (Cmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC	231 mg/L Standard Deviation 55.3	—	—

SECONDARY outcome

Timeframe: on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion

Population: PK analysis subset

The time at which maximum concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered, is reached (Tmax).

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=8 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Time of Cmax (Tmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC	0.23 days Standard Deviation 0.11	—	—

SECONDARY outcome

Timeframe: on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion

Population: PK analysis subset with adequate data for this analysis

Terminal phase plasma half-life (t ½) is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, rather than the time required to eliminate half the administered dose.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=6 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Terminal Phase Plasma Half-life (t ½) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC	17.9 days Standard Deviation 2.18	—	—

SECONDARY outcome

Timeframe: on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion

Population: Pharmacokinetic analysis subset with appropriate data available

Bioavailability [AUC(0-t)] is a measure of how much of the drug reaches the person's bloodstream from time 0 (pre-dose) to a given time point (t) for the body to use. The extent of product bioavailability is estimated by the area under the blood concentration vs time curve. The Area Under the Curve (AUC) is calculated by plotting the drug's blood levels on a graph at different times during the set period. The area under this curve reflects the amount of drug exposure in the set time period, calculated as hour * nanograms (ng) per milliliter (mL), which equates to mg.day/L. Bioavailability Extrapolated to Infinity [AUC (0-inf)] is a calculated measure of how much of the drug will ever reach the person's bloodstream for the body to use. AUC (0-inf) stands for the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (forever). It is obtained from calculating AUC (0-t) plus AUC (t-inf).

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=8 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Area Under the Plasma Concentration Versus Time Curve (AUC) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With Non-small Cell Lung Cancer (NSCLC) AUC(0-21 days) n=8	1780 mg*day/L Standard Deviation 340	—	—
Area Under the Plasma Concentration Versus Time Curve (AUC) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With Non-small Cell Lung Cancer (NSCLC) AUC(0-inf) n=7	3000 mg*day/L Standard Deviation 815	—	—

SECONDARY outcome

Timeframe: on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion

Population: PK subset

A fundamental concept in pharmacokinetics is drug clearance (CL), that is, elimination of drugs from the body. The clearance is simply the ratio of the dose to the area under the curve (AUC), so that the higher the AUC for a given dose, the lower the clearance. If a drug is administered by continuous infusion and a steady state is achieved, the clearance can be estimated from a single measurement of the plasma drug concentration.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=8 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Clearance (CL) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC	0.24 L/day Standard Deviation 0.05	—	—

SECONDARY outcome

Timeframe: on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion

Population: PK analysis subset

Steady-state volume of distribution of a drug is an estimate of drug distribution independent of elimination processes. It is most useful for predicting the plasma concentrations following multiple dosing to a steady-state or pseudo-equilibrium. Vss is proportional to the amount of drug in the body versus the plasma concentration of the drug at steady state (pseudo-equilibrium). It is a calculated measure.

Outcome measures

Measure	Erlotinib 100 mg + Pertuzumab 420 mg n=8 Participants Participants received erlotinib 100 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.	Erlotinib 150 mg + Pertuzumab 420 mg Participants received erlotinib 150 mg orally once daily plus pertuzumab 420 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or the participant withdrew from the study. The first dose of pertuzumab was a loading dose of 840 mg intravenously.
Volume of Distribution at Steady-state (Vss) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC	4.9 Liters Standard Deviation 1.3	—	—

Adverse Events

Cohort 1

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 2

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1 n=6 participants at risk Erlotinib 100 mg + pertuzumab 420 mg	Cohort 2 n=9 participants at risk Erlotinib 150 mg + pertuzumab 420 mg
Renal and urinary disorders Renal Failure Acute	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Cancer Malignant	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Cardiac disorders Myocardial Infarction	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Vascular disorders Thrombosis	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.

Other adverse events

Measure	Cohort 1 n=6 participants at risk Erlotinib 100 mg + pertuzumab 420 mg	Cohort 2 n=9 participants at risk Erlotinib 150 mg + pertuzumab 420 mg
Gastrointestinal disorders Diarrhea	50.0% 3/6 • Number of events 3 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	66.7% 6/9 • Number of events 6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	33.3% 3/9 • Number of events 3 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Abdominal Pain Upper	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	22.2% 2/9 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Nausea	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	22.2% 2/9 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Abdominal Pain	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Anal Fissure	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Constipation	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Skin and subcutaneous tissue disorders Rash	100.0% 6/6 • Number of events 6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	55.6% 5/9 • Number of events 5 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Skin and subcutaneous tissue disorders Pruritus	66.7% 4/6 • Number of events 4 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	22.2% 2/9 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Skin and subcutaneous tissue disorders Nail Bed Inflammation	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	22.2% 2/9 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Skin and subcutaneous tissue disorders Dry Skin	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
General disorders Asthenia	33.3% 2/6 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	33.3% 3/9 • Number of events 3 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
General disorders Mucosal Inflammation	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
General disorders Axillary Pain	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
General disorders Oedema	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
General disorders Pain	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Nervous system disorders Headache	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	44.4% 4/9 • Number of events 4 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Nervous system disorders Lethargy	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Nervous system disorders Neurotoxicity	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Nervous system disorders Peripheral Sensory Neuropathy	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Paronychia	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Fungal Infection	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Influenza	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Lung Infection	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Nail Infection	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Onychomycosis	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Oral Fungal Infection	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Infections and infestations Tinea Pedis	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	22.2% 2/9 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Metabolism and nutrition disorders Anorexia	33.3% 2/6 • Number of events 2 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	33.3% 3/9 • Number of events 3 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Musculoskeletal and connective tissue disorders Bone Pain	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Psychiatric disorders Depression	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Eye disorders Xerophthalmia	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Injury, poisoning and procedural complications Contusion	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Vascular disorders Hypertension	16.7% 1/6 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	0.00% 0/9 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/6 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.	11.1% 1/9 • Number of events 1 • Timeframe was up to 42 weeks All participants who received at least 1 dose of both pertuzumab and erlotinib and had at least 1 post-baseline safety follow-up.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER