Trial Outcomes & Findings for Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer (NCT NCT01708954)

Last Updated: 2025-11-10

Results Overview

PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date of last disease assessment.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

125 participants

Primary outcome timeframe

Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Results posted on

2025-11-10

Participant Flow

This study was activated on February 7, 2013 and closed to accrual on July 1, 2014 with final accrual of 125 patients. Among these, a total of 20 patients registered to Step 2.

Participant milestones

Participant milestones
Measure	Arm A (Erlotinib) Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Step 1 STARTED	42	40	43
Step 1 Started Protocol Therapy	40	40	39
Step 1 Eligible and Treated	38	38	35
Step 1 Patients With MET Status Data Available	30	32	24
Step 1 COMPLETED	0	0	0
Step 1 NOT COMPLETED	42	40	43
Step 2 STARTED	13	7	0
Step 2 COMPLETED	0	0	0
Step 2 NOT COMPLETED	13	7	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Erlotinib) Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Step 1 Disease progression	26	17	14
Step 1 Adverse Event	3	11	13
Step 1 Death	3	2	3
Step 1 Withdrawal by Subject	2	5	3
Step 1 Other complicating disease	0	2	0
Step 1 Crossed over to Step 2	2	0	0
Step 1 Symptomatic deterioration	1	0	1
Step 1 Off-treatment reason not submitted	1	1	1
Step 1 Ineligible or never received treatment	4	2	8
Step 2 Disease progression	9	4	0
Step 2 Adverse Event	3	2	0
Step 2 Withdrawal by Subject	1	1	0

Baseline Characteristics

Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Erlotinib) n=38 Participants Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) n=38 Participants Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) n=35 Participants Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total n=111 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	65 years n=20 Participants	63 years n=40 Participants	66 years n=28 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	24 Participants n=20 Participants	17 Participants n=40 Participants	61 Participants n=28 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	14 Participants n=20 Participants	18 Participants n=40 Participants	50 Participants n=28 Participants

PRIMARY outcome

Timeframe: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Population: Eligible and treated patients

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib) n=38 Participants Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) n=38 Participants Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) n=35 Participants Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS)	1.8 months Interval 1.7 to 2.2	4.3 months Interval 3.6 to 7.4	4.7 months Interval 2.4 to 7.4

SECONDARY outcome

Timeframe: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Population: Eligible and treated patients

OS is defined as the time from randomization to death from any cause or date of last known alive.

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib) n=38 Participants Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) n=38 Participants Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) n=35 Participants Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS)	5.1 months Interval 3.3 to 9.3	9.2 months Interval 5.1 to 15.0	13.3 months Interval 7.6 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Population: Eligible and treated patients

Objective response is defined as complete response (CR) or partial response (PR) evaluated using RECIST v 1.1. CR is defined as disappearance of all lesions and any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions and persistence of one or more non-target lesion(s).

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib) n=38 Participants Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) n=38 Participants Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) n=35 Participants Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Objective Response	0.03 proportion of participants Interval 0.0009 to 0.141	0.11 proportion of participants Interval 0.03 to 0.25	0.03 proportion of participants Interval 0.001 to 0.15

SECONDARY outcome

Timeframe: Assessed at baseline

Population: Eligible and treated patients who had sufficient samples for MET expression analysis.

Submission of archival tissue for central MET IHC testing was required for this study, and total MET IHC testing was conducted at the Brigham and Women's Hospital using the c-Met clone CVD13 (arabbit polyclonal). Membranous and cytoplasmic staining were individually scored, and positivity was declared if MET was expressed in either the membrane or cytoplasm.

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib) n=30 Participants Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) n=32 Participants Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) n=24 Participants Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With MET Positivity	0.80 proportion of participants Interval 0.61 to 0.92	0.81 proportion of participants Interval 0.64 to 0.93	0.96 proportion of participants Interval 0.79 to 0.999

SECONDARY outcome

Timeframe: Assessed every 4 weeks while on treatment and for 30 days after the end of treatment

Population: All patients who received protocol therapy

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib) n=40 Participants Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cabozantinib) n=40 Participants Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm C (Erlotinib+Cabozantinib) n=39 Participants Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher	0.325 Proportion of participants Interval 0.204 to 0.466	0.70 Proportion of participants Interval 0.56 to 0.817	0.718 Proportion of participants Interval 0.577 to 0.833

Adverse Events

Arm A (Erlotinib)

Serious events: 13 serious events

Other events: 35 other events

Deaths: 0 deaths

Arm B (Cabozantinib)

Serious events: 28 serious events

Other events: 40 other events

Deaths: 0 deaths

Arm C (Erlotinib+Cabozantinib)

Serious events: 28 serious events

Other events: 38 other events

Deaths: 0 deaths

Arm Z (Erlotinib+Cabozantinib; Step 2)

Serious events: 12 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60