Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer 1: Final patient-level results from Japan Clinical Oncology Group 9511 and Southwest oncology group 0124

Primo N Lara, Kari Chansky, Taro Shibata, Haruhiko Fukuda, Tomohide Tamura, John Crowley, Mary W. Redman, Ronald Natale, Nagahiro Saijo, David R Gandara

Research output: Contribution to journalArticle

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Abstract

Background: Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results. Methods: Patients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m2 Day 1 + irinotecan 60 mg/m2 Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m 2 Day 1 + etoposide 100 mg/m2 Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS). Results: Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared. Conclusions: Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected.

Original languageEnglish (US)
Pages (from-to)5710-5715
Number of pages6
JournalCancer
Volume116
Issue number24
DOIs
StatePublished - Dec 15 2010

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irinotecan
Medical Oncology
Small Cell Lung Carcinoma
Etoposide
Cisplatin
Japan
Demography

Keywords

  • chemotherapy
  • cisplatin
  • extensive stage
  • irinotecan
  • small cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer 1 : Final patient-level results from Japan Clinical Oncology Group 9511 and Southwest oncology group 0124. / Lara, Primo N; Chansky, Kari; Shibata, Taro; Fukuda, Haruhiko; Tamura, Tomohide; Crowley, John; Redman, Mary W.; Natale, Ronald; Saijo, Nagahiro; Gandara, David R.

In: Cancer, Vol. 116, No. 24, 15.12.2010, p. 5710-5715.

Research output: Contribution to journalArticle

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abstract = "Background: Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results. Methods: Patients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m2 Day 1 + irinotecan 60 mg/m2 Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m 2 Day 1 + etoposide 100 mg/m2 Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS). Results: Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87{\%} vs 60{\%}, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared. Conclusions: Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected.",
keywords = "chemotherapy, cisplatin, extensive stage, irinotecan, small cell lung cancer",
author = "Lara, {Primo N} and Kari Chansky and Taro Shibata and Haruhiko Fukuda and Tomohide Tamura and John Crowley and Redman, {Mary W.} and Ronald Natale and Nagahiro Saijo and Gandara, {David R}",
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AU - Lara, Primo N

AU - Chansky, Kari

AU - Shibata, Taro

AU - Fukuda, Haruhiko

AU - Tamura, Tomohide

AU - Crowley, John

AU - Redman, Mary W.

AU - Natale, Ronald

AU - Saijo, Nagahiro

AU - Gandara, David R

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KW - chemotherapy

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