Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer

© 2016 The Authors. Objectives: The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were...

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Main Authors: Mok T., Ladrera G., Srimuninnimit V., Sriuranpong V., Yu C., Thongprasert S., Sandoval-Tan J., Lee J., Fuerte F., Shames D., Klughammer B., Truman M., Perez-Moreno P., Wu Y.
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Published: 2017
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/41699
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spelling th-cmuir.6653943832-416992017-09-28T04:22:53Z Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer Mok T. Ladrera G. Srimuninnimit V. Sriuranpong V. Yu C. Thongprasert S. Sandoval-Tan J. Lee J. Fuerte F. Shames D. Klughammer B. Truman M. Perez-Moreno P. Wu Y. © 2016 The Authors. Objectives: The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight. Materials and methods: This multicenter, randomized, placebo-controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas ® test, KRAS mutation by cobas ® KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate. Results: Overall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations (p < 0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR = 0.32, 95% confidence intervals [CI] : 0.14-0.69, p = 0.0024). Conclusion: Activating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation. 2017-09-28T04:22:53Z 2017-09-28T04:22:53Z 2016-08-01 Journal 01695002 2-s2.0-84966701371 10.1016/j.lungcan.2016.04.023 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84966701371&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/41699
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description © 2016 The Authors. Objectives: The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight. Materials and methods: This multicenter, randomized, placebo-controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas ® test, KRAS mutation by cobas ® KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate. Results: Overall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations (p < 0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR = 0.32, 95% confidence intervals [CI] : 0.14-0.69, p = 0.0024). Conclusion: Activating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation.
format Journal
author Mok T.
Ladrera G.
Srimuninnimit V.
Sriuranpong V.
Yu C.
Thongprasert S.
Sandoval-Tan J.
Lee J.
Fuerte F.
Shames D.
Klughammer B.
Truman M.
Perez-Moreno P.
Wu Y.
spellingShingle Mok T.
Ladrera G.
Srimuninnimit V.
Sriuranpong V.
Yu C.
Thongprasert S.
Sandoval-Tan J.
Lee J.
Fuerte F.
Shames D.
Klughammer B.
Truman M.
Perez-Moreno P.
Wu Y.
Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
author_facet Mok T.
Ladrera G.
Srimuninnimit V.
Sriuranpong V.
Yu C.
Thongprasert S.
Sandoval-Tan J.
Lee J.
Fuerte F.
Shames D.
Klughammer B.
Truman M.
Perez-Moreno P.
Wu Y.
author_sort Mok T.
title Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
title_short Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
title_full Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
title_fullStr Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
title_full_unstemmed Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
title_sort tumor marker analyses from the phase iii, placebo-controlled, fastact-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer
publishDate 2017
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84966701371&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/41699
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