Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer

Yi Long Wu, James Chih Hsin Yang, Dong Wan Kim, Shun Lu, Jianying Zhou, Takashi Seto, Jin Ji Yang, Noboru Yamamoto, Myung Ju Ahn, Toshiaki Takahashi, Takeharu Yamanaka, Allison Kemner, Debasish Roychowdhury, Jolanda Paolini, Tiziana Usari, Keith D. Wilner, Koichi Goto

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Abstract

Purpose Approximately 1% to 2% of non–small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 (ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1–defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.

Original languageEnglish
Pages (from-to)1405-1411
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number14
DOIs
StatePublished - 1 Jan 2018

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Non-Small Cell Lung Carcinoma
Radiology
Safety
Therapeutics
crizotinib
Oncogenes
Disease-Free Survival
China

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Wu, Yi Long ; Yang, James Chih Hsin ; Kim, Dong Wan ; Lu, Shun ; Zhou, Jianying ; Seto, Takashi ; Yang, Jin Ji ; Yamamoto, Noboru ; Ahn, Myung Ju ; Takahashi, Toshiaki ; Yamanaka, Takeharu ; Kemner, Allison ; Roychowdhury, Debasish ; Paolini, Jolanda ; Usari, Tiziana ; Wilner, Keith D. ; Goto, Koichi. / Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 14. pp. 1405-1411.
@article{5bf6802c2da2400f9147d0cb1978f4d9,
title = "Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer",
abstract = "Purpose Approximately 1{\%} to 2{\%} of non–small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 (ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1–defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6{\%} still receiving treatment at data cutoff. ORR by IRR was 71.7{\%} (95{\%} CI, 63.0{\%} to 79.3{\%}), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95{\%} CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95{\%} CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.",
author = "Wu, {Yi Long} and Yang, {James Chih Hsin} and Kim, {Dong Wan} and Shun Lu and Jianying Zhou and Takashi Seto and Yang, {Jin Ji} and Noboru Yamamoto and Ahn, {Myung Ju} and Toshiaki Takahashi and Takeharu Yamanaka and Allison Kemner and Debasish Roychowdhury and Jolanda Paolini and Tiziana Usari and Wilner, {Keith D.} and Koichi Goto",
year = "2018",
month = "1",
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doi = "10.1200/JCO.2017.75.5587",
language = "English",
volume = "36",
pages = "1405--1411",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "14",

}

Wu, YL, Yang, JCH, Kim, DW, Lu, S, Zhou, J, Seto, T, Yang, JJ, Yamamoto, N, Ahn, MJ, Takahashi, T, Yamanaka, T, Kemner, A, Roychowdhury, D, Paolini, J, Usari, T, Wilner, KD & Goto, K 2018, 'Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer', Journal of Clinical Oncology, vol. 36, no. 14, pp. 1405-1411. https://doi.org/10.1200/JCO.2017.75.5587

Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer. / Wu, Yi Long; Yang, James Chih Hsin; Kim, Dong Wan; Lu, Shun; Zhou, Jianying; Seto, Takashi; Yang, Jin Ji; Yamamoto, Noboru; Ahn, Myung Ju; Takahashi, Toshiaki; Yamanaka, Takeharu; Kemner, Allison; Roychowdhury, Debasish; Paolini, Jolanda; Usari, Tiziana; Wilner, Keith D.; Goto, Koichi.

In: Journal of Clinical Oncology, Vol. 36, No. 14, 01.01.2018, p. 1405-1411.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II study of crizotinib in east asian patients with ROS1-positive advanced non–small-cell lung cancer

AU - Wu, Yi Long

AU - Yang, James Chih Hsin

AU - Kim, Dong Wan

AU - Lu, Shun

AU - Zhou, Jianying

AU - Seto, Takashi

AU - Yang, Jin Ji

AU - Yamamoto, Noboru

AU - Ahn, Myung Ju

AU - Takahashi, Toshiaki

AU - Yamanaka, Takeharu

AU - Kemner, Allison

AU - Roychowdhury, Debasish

AU - Paolini, Jolanda

AU - Usari, Tiziana

AU - Wilner, Keith D.

AU - Goto, Koichi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose Approximately 1% to 2% of non–small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 (ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1–defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.

AB - Purpose Approximately 1% to 2% of non–small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 (ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1–defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.

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U2 - 10.1200/JCO.2017.75.5587

DO - 10.1200/JCO.2017.75.5587

M3 - Article

C2 - 29596029

AN - SCOPUS:85047118567

VL - 36

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EP - 1411

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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