Yukio Hosomi1, Satoshi Morita2, Shunichi Sugawara3, Terufumi Kato4, Tatsuro Fukuhara5, Akihiko Gemma6, Kazuhisa Takahashi7, Yuka Fujita8, Toshiyuki Harada9, Koichi Minato10, Kei Takamura11, Koichi Hagiwara12, Kunihiko Kobayashi13, Toshihiro Nukiwa14, Akira Inoue15. 1. Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. 2. Kyoto University Graduate School of Medicine, Kyoto, Japan. 3. Sendai Kousei Hospital, Sendai, Japan. 4. Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. 5. Miyagi Cancer Center, Natori, Japan. 6. Nippon Medical School, Tokyo, Japan. 7. Juntendo University Graduate School of Medicine, Tokyo, Japan. 8. Asahikawa Medical Center, Asahikawa, Japan. 9. Japan Community Health Care Organization Hokkaido Hospital, Sapporo, Japan. 10. Gunma Prefectural Cancer Center, Ota, Japan. 11. Obihiro Kosei General Hospital, Obihiro, Japan. 12. Jichi Medical University, Shimotsuke, Japan. 13. Saitama Medical University, Hidaka, Japan. 14. Tohoku University, Sendai, Japan. 15. Tohoku University School of Medicine, Sendai, Japan.
Abstract
PURPOSE:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone. METHODS: We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined withcarboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life. RESULTS: The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% v 67% [P < .001]; PFS, 20.9 v 11.9 months; hazard ratio for death or disease progression, 0.490 [P < .001]), although PFS2 was not significantly different (20.9 v 18.0 months; P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months; hazard ratio for death, 0.722; P = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group. CONCLUSION: Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.
RCT Entities:
PURPOSE:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone. METHODS: We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life. RESULTS: The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% v 67% [P < .001]; PFS, 20.9 v 11.9 months; hazard ratio for death or disease progression, 0.490 [P < .001]), although PFS2 was not significantly different (20.9 v 18.0 months; P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months; hazard ratio for death, 0.722; P = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group. CONCLUSION: Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.
Authors: Anna Buder; Ellen Heitzer; Julie Waldispühl-Geigl; Sabrina Weber; Tina Moser; Maximilian J Hochmair; Klaus Hackner; Peter Errhalt; Ulrike Setinek; Martin Filipits Journal: Biomolecules Date: 2021-04-21
Authors: Maya N White; Zofia Piotrowska; Kevin Stirling; Stephen V Liu; Mandeep K Banwait; Kristen Cunanan; Lecia V Sequist; Heather A Wakelee; Daniel Hausrath; Joel W Neal Journal: Clin Lung Cancer Date: 2021-01-27 Impact factor: 4.785