Takashi Seto1, Koichi Azuma2, Takeharu Yamanaka3, Shunichi Sugawara4, Hiroshige Yoshioka5, Kazushige Wakuda6, Shinji Atagi7, Yasuo Iwamoto8, Hidetoshi Hayashi9, Isamu Okamoto10, Hideo Saka11, Shigeki Mitsuoka12, Daichi Fujimoto13, Kazumi Nishino14, Atsushi Horiike15, Haruko Daga16, Takashi Sone17, Nobuyuki Yamamoto18, Kazuhiko Nakagawa19, Yoichi Nakanishi20. 1. National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 2. Kurume University School of Medicine, Kurume, Japan. 3. Yokohama City University, Yokohama, Japan. 4. Sendai Kousei Hospital, Sendai, Japan. 5. Kansai Medical University Hospital, Hirakata, Japan. 6. Shizuoka Cancer Center, Shizuoka, Japan. 7. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan. 8. Hiroshima Citizens Hospital, Hiroshima, Japan. 9. Kindai University Faculty of Medicine, Osaka, Japan. 10. Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 11. National Hospital Organization, Nagoya Medical Center, Nagoya, Japan. 12. Osaka City University Hospital, Osaka, Japan. 13. Kobe City Medical Center General Hospital, Kobe, Japan. 14. Osaka International Cancer Institute, Osaka, Japan. 15. The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 16. Osaka City General Hospital, Osaka, Japan. 17. Kanazawa University Hospital, Kanazawa, Japan. 18. Wakayama Medical University, Wakayama, Japan. 19. Kindai University Hospital, Osaka, Japan. 20. Kyushu University Hospital, Fukuoka, Japan.
Abstract
PURPOSE:Patients with non-small-cell lung cancer (NSCLC) have been shown to benefit from maintenance therapy. COMPASS evaluated the efficacy and safety of bevacizumab with or without pemetrexed as continuation maintenance therapy after carboplatin, pemetrexed, and bevacizumab induction therapy. PATIENTS AND METHODS: Patients with untreated advanced nonsquamous NSCLC without confirmed EGFR 19 deletion or L858R mutation received first-line therapy with carboplatin area under the curve 6, pemetrexed 500 mg/m2, and bevacizumab 15 mg/kg once every 3 weeks for 4 cycles. Patients without disease progression during the induction therapy were randomly assigned 1:1 for maintenance therapy with pemetrexed 500 mg/m2 plus bevacizumab 15 mg/kg or bevacizumab 15 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) after random assignment. RESULTS:Between September 2010 and September 2015, 907 patients receivedinduction therapy. Of those, 599 were randomly assigned: 298 received pemetrexed plus bevacizumab, and 301 received bevacizumab. The median OS was 23.3 v 19.6 months (hazard ratio [HR], 0.87; 95% CI, 0.73 to 1.05; 1-sided stratified log-rank P = .069). In the wild-type EGFR subset, the OS HR was 0.82 (95% CI, 0.68 to 0.99; 1-sided unstratified log-rank P = .020). The median progression-free survival (PFS) was 5.7 v 4.0 months (HR, 0.67; 95% CI, 0.57 to 0.79; 2-sided log-rank P < .001). The safety data were consistent with previous reports of treatment regimens. CONCLUSION: In terms of the primary end point of OS, no statistically significant benefit was observed; however, PFS in the total patient population and OS in patients with wild-type EGFR was prolonged with the addition of pemetrexed to bevacizumab maintenance therapy.
RCT Entities:
PURPOSE:Patients with non-small-cell lung cancer (NSCLC) have been shown to benefit from maintenance therapy. COMPASS evaluated the efficacy and safety of bevacizumab with or without pemetrexed as continuation maintenance therapy after carboplatin, pemetrexed, and bevacizumab induction therapy. PATIENTS AND METHODS: Patients with untreated advanced nonsquamous NSCLC without confirmed EGFR 19 deletion or L858R mutation received first-line therapy with carboplatin area under the curve 6, pemetrexed 500 mg/m2, and bevacizumab 15 mg/kg once every 3 weeks for 4 cycles. Patients without disease progression during the induction therapy were randomly assigned 1:1 for maintenance therapy with pemetrexed 500 mg/m2 plus bevacizumab 15 mg/kg or bevacizumab 15 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) after random assignment. RESULTS: Between September 2010 and September 2015, 907 patients received induction therapy. Of those, 599 were randomly assigned: 298 received pemetrexed plus bevacizumab, and 301 received bevacizumab. The median OS was 23.3 v 19.6 months (hazard ratio [HR], 0.87; 95% CI, 0.73 to 1.05; 1-sided stratified log-rank P = .069). In the wild-type EGFR subset, the OS HR was 0.82 (95% CI, 0.68 to 0.99; 1-sided unstratified log-rank P = .020). The median progression-free survival (PFS) was 5.7 v 4.0 months (HR, 0.67; 95% CI, 0.57 to 0.79; 2-sided log-rank P < .001). The safety data were consistent with previous reports of treatment regimens. CONCLUSION: In terms of the primary end point of OS, no statistically significant benefit was observed; however, PFS in the total patient population and OS in patients with wild-type EGFR was prolonged with the addition of pemetrexed to bevacizumab maintenance therapy.