SWOG S0709: Randomized phase II trial of erlotinib versus erlotinib plus carboplatin/paclitaxel in patients with advanced non-small cell lung cancer and impaired performance status as selected by a serum proteomics assay

Primo N Lara, James Moon, Paul J. Hesketh, Mary W. Redman, Stephen K. Williamson, Wallace L. Akerley, Fred R. Hirsch, Philip Mack, David R Gandara

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy. In light of the potential role for serum proteomics in predicting the benefit of erlotinib beyond that of epidermal growth factor receptor gene (EGFR) mutational status, we conducted a trial in which the Veristrat proteomics assay was used for data enrichment when selecting a cohort of patients with NSCLC and PS2 to receive erlotinib with and without chemotherapy. Methods: Patients with metastatic NSCLC, PS2, acceptable end-organ function, and Veristrat-good status were randomly assigned to receive either 150 mg of erlotinib orally daily (arm 1) or 150 mg of erlotinib orally daily on days 2 through16 plus four cycles of carboplatin (area under the curve=5 on day 1) and paclitaxel (200 mg/m2 intravenously on day 1) followed by 150 mg of erlotinib orally (arm 2). The arm 2 agents were pharmacodynamically separated to mitigate potential antagonism. The arm with superior observed median progression-free survival (PFS) would be selected for further evaluation, but only if PFS lasted for at least 3 months. Results: The trial terminated before the planned accrual of 98 patients for regulatory reasons. A total of 156 patients were screened. Of the 83 (59%) who were classified as Veristrat good, 59 met the trial eligibility criteria and were randomly assigned to one of two arms (33 patients in arm 1 and 26 in arm 2). The patients in arm 2 patients had a higher response rate (23% versus 6%, p=0.06), disease control rate (77% versus 41%, p = 0.0046), median PFS (4.6 versus 1.6 months, p = 0.06), and median overall survival (11 versus 6 months, p = 0.27). Treatment-related grade 4 adverse events were seen in two patients in arm 1 (thrombosis and hypomagnesemia) and in five patients in arm 2 (neutropenia in five, febrile neutropenia in one, and leukopenia in one). Conclusions: In a proteomics-enriched cohort of patients with NSCLC and PS2, pharmacodynamically separated erlotinib plus chemotherapy had better efficacy than did erlotinib alone and surpassed the protocol-specified benchmark of PFS of at least 3 months required for further study.

Original languageEnglish (US)
Pages (from-to)420-425
Number of pages6
JournalJournal of Thoracic Oncology
Volume11
Issue number3
DOIs
StatePublished - Mar 23 2016

Fingerprint

Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Proteomics
Serum
Disease-Free Survival
Erlotinib Hydrochloride
erbB-1 Genes
Benchmarking
Drug Therapy
Febrile Neutropenia
Leukopenia
Neutropenia
Platinum
Area Under Curve
Thrombosis
Clinical Trials

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

SWOG S0709 : Randomized phase II trial of erlotinib versus erlotinib plus carboplatin/paclitaxel in patients with advanced non-small cell lung cancer and impaired performance status as selected by a serum proteomics assay. / Lara, Primo N; Moon, James; Hesketh, Paul J.; Redman, Mary W.; Williamson, Stephen K.; Akerley, Wallace L.; Hirsch, Fred R.; Mack, Philip; Gandara, David R.

In: Journal of Thoracic Oncology, Vol. 11, No. 3, 23.03.2016, p. 420-425.

Research output: Contribution to journalReview article

@article{e74f5b6100d84cb7862f95ae020fc9d5,
title = "SWOG S0709: Randomized phase II trial of erlotinib versus erlotinib plus carboplatin/paclitaxel in patients with advanced non-small cell lung cancer and impaired performance status as selected by a serum proteomics assay",
abstract = "Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy. In light of the potential role for serum proteomics in predicting the benefit of erlotinib beyond that of epidermal growth factor receptor gene (EGFR) mutational status, we conducted a trial in which the Veristrat proteomics assay was used for data enrichment when selecting a cohort of patients with NSCLC and PS2 to receive erlotinib with and without chemotherapy. Methods: Patients with metastatic NSCLC, PS2, acceptable end-organ function, and Veristrat-good status were randomly assigned to receive either 150 mg of erlotinib orally daily (arm 1) or 150 mg of erlotinib orally daily on days 2 through16 plus four cycles of carboplatin (area under the curve=5 on day 1) and paclitaxel (200 mg/m2 intravenously on day 1) followed by 150 mg of erlotinib orally (arm 2). The arm 2 agents were pharmacodynamically separated to mitigate potential antagonism. The arm with superior observed median progression-free survival (PFS) would be selected for further evaluation, but only if PFS lasted for at least 3 months. Results: The trial terminated before the planned accrual of 98 patients for regulatory reasons. A total of 156 patients were screened. Of the 83 (59{\%}) who were classified as Veristrat good, 59 met the trial eligibility criteria and were randomly assigned to one of two arms (33 patients in arm 1 and 26 in arm 2). The patients in arm 2 patients had a higher response rate (23{\%} versus 6{\%}, p=0.06), disease control rate (77{\%} versus 41{\%}, p = 0.0046), median PFS (4.6 versus 1.6 months, p = 0.06), and median overall survival (11 versus 6 months, p = 0.27). Treatment-related grade 4 adverse events were seen in two patients in arm 1 (thrombosis and hypomagnesemia) and in five patients in arm 2 (neutropenia in five, febrile neutropenia in one, and leukopenia in one). Conclusions: In a proteomics-enriched cohort of patients with NSCLC and PS2, pharmacodynamically separated erlotinib plus chemotherapy had better efficacy than did erlotinib alone and surpassed the protocol-specified benchmark of PFS of at least 3 months required for further study.",
author = "Lara, {Primo N} and James Moon and Hesketh, {Paul J.} and Redman, {Mary W.} and Williamson, {Stephen K.} and Akerley, {Wallace L.} and Hirsch, {Fred R.} and Philip Mack and Gandara, {David R}",
year = "2016",
month = "3",
day = "23",
doi = "10.1016/j.jtho.2015.11.003",
language = "English (US)",
volume = "11",
pages = "420--425",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "3",

}

TY - JOUR

T1 - SWOG S0709

T2 - Randomized phase II trial of erlotinib versus erlotinib plus carboplatin/paclitaxel in patients with advanced non-small cell lung cancer and impaired performance status as selected by a serum proteomics assay

AU - Lara, Primo N

AU - Moon, James

AU - Hesketh, Paul J.

AU - Redman, Mary W.

AU - Williamson, Stephen K.

AU - Akerley, Wallace L.

AU - Hirsch, Fred R.

AU - Mack, Philip

AU - Gandara, David R

PY - 2016/3/23

Y1 - 2016/3/23

N2 - Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy. In light of the potential role for serum proteomics in predicting the benefit of erlotinib beyond that of epidermal growth factor receptor gene (EGFR) mutational status, we conducted a trial in which the Veristrat proteomics assay was used for data enrichment when selecting a cohort of patients with NSCLC and PS2 to receive erlotinib with and without chemotherapy. Methods: Patients with metastatic NSCLC, PS2, acceptable end-organ function, and Veristrat-good status were randomly assigned to receive either 150 mg of erlotinib orally daily (arm 1) or 150 mg of erlotinib orally daily on days 2 through16 plus four cycles of carboplatin (area under the curve=5 on day 1) and paclitaxel (200 mg/m2 intravenously on day 1) followed by 150 mg of erlotinib orally (arm 2). The arm 2 agents were pharmacodynamically separated to mitigate potential antagonism. The arm with superior observed median progression-free survival (PFS) would be selected for further evaluation, but only if PFS lasted for at least 3 months. Results: The trial terminated before the planned accrual of 98 patients for regulatory reasons. A total of 156 patients were screened. Of the 83 (59%) who were classified as Veristrat good, 59 met the trial eligibility criteria and were randomly assigned to one of two arms (33 patients in arm 1 and 26 in arm 2). The patients in arm 2 patients had a higher response rate (23% versus 6%, p=0.06), disease control rate (77% versus 41%, p = 0.0046), median PFS (4.6 versus 1.6 months, p = 0.06), and median overall survival (11 versus 6 months, p = 0.27). Treatment-related grade 4 adverse events were seen in two patients in arm 1 (thrombosis and hypomagnesemia) and in five patients in arm 2 (neutropenia in five, febrile neutropenia in one, and leukopenia in one). Conclusions: In a proteomics-enriched cohort of patients with NSCLC and PS2, pharmacodynamically separated erlotinib plus chemotherapy had better efficacy than did erlotinib alone and surpassed the protocol-specified benchmark of PFS of at least 3 months required for further study.

AB - Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy. In light of the potential role for serum proteomics in predicting the benefit of erlotinib beyond that of epidermal growth factor receptor gene (EGFR) mutational status, we conducted a trial in which the Veristrat proteomics assay was used for data enrichment when selecting a cohort of patients with NSCLC and PS2 to receive erlotinib with and without chemotherapy. Methods: Patients with metastatic NSCLC, PS2, acceptable end-organ function, and Veristrat-good status were randomly assigned to receive either 150 mg of erlotinib orally daily (arm 1) or 150 mg of erlotinib orally daily on days 2 through16 plus four cycles of carboplatin (area under the curve=5 on day 1) and paclitaxel (200 mg/m2 intravenously on day 1) followed by 150 mg of erlotinib orally (arm 2). The arm 2 agents were pharmacodynamically separated to mitigate potential antagonism. The arm with superior observed median progression-free survival (PFS) would be selected for further evaluation, but only if PFS lasted for at least 3 months. Results: The trial terminated before the planned accrual of 98 patients for regulatory reasons. A total of 156 patients were screened. Of the 83 (59%) who were classified as Veristrat good, 59 met the trial eligibility criteria and were randomly assigned to one of two arms (33 patients in arm 1 and 26 in arm 2). The patients in arm 2 patients had a higher response rate (23% versus 6%, p=0.06), disease control rate (77% versus 41%, p = 0.0046), median PFS (4.6 versus 1.6 months, p = 0.06), and median overall survival (11 versus 6 months, p = 0.27). Treatment-related grade 4 adverse events were seen in two patients in arm 1 (thrombosis and hypomagnesemia) and in five patients in arm 2 (neutropenia in five, febrile neutropenia in one, and leukopenia in one). Conclusions: In a proteomics-enriched cohort of patients with NSCLC and PS2, pharmacodynamically separated erlotinib plus chemotherapy had better efficacy than did erlotinib alone and surpassed the protocol-specified benchmark of PFS of at least 3 months required for further study.

UR - http://www.scopus.com/inward/record.url?scp=84962514312&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962514312&partnerID=8YFLogxK

U2 - 10.1016/j.jtho.2015.11.003

DO - 10.1016/j.jtho.2015.11.003

M3 - Review article

C2 - 26725184

AN - SCOPUS:84962514312

VL - 11

SP - 420

EP - 425

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 3

ER -