Takashi Onda1, Toyomi Satoh2, Gakuto Ogawa3, Toshiaki Saito4, Takahiro Kasamatsu5, Toru Nakanishi6, Tomonori Mizutani3, Kazuhiro Takehara7, Aikou Okamoto8, Kimio Ushijima9, Hiroaki Kobayashi10, Kei Kawana11, Harushige Yokota12, Masashi Takano13, Hiroyuki Kanao14, Yoh Watanabe15, Kaichiro Yamamoto16, Nobuo Yaegashi17, Toshiharu Kamura18, Hiroyuki Yoshikawa19. 1. Department of Gynecology, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address: takashi-tky@umin.ac.jp. 2. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 3. JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan. 4. Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 5. Department of Gynecologic Oncology, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 7. Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 8. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan. 9. Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan. 10. Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 11. Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. 12. Department of Gynecology, Saitama Cancer Center, Kita Adachi Gun, Japan. 13. Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Japan. 14. Department of Gynecological Oncology, Cancer Institute Hospital, Tokyo, Japan. 15. Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Japan. 16. Department of Obstetrics and Gynecology, Faculty of Medicine, Kindai University, Sakai Hospital, Sakai, Japan. 17. Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan. 18. Medical Care Education Research Foundation, Yanagawa Hospital, Yanagawa, Japan. 19. Ibaraki Prefectural Central Hospital, Kasama, Japan.
Abstract
BACKGROUND: Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS). METHODS: Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300. FINDINGS:Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour <1 cm) was achieved in 37% (55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum albumin ≤2·5, CA125 > 2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS. INTERPRETATION: The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied. FUNDING: Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan. CLINICAL TRIAL INFORMATION: UMIN000000523.
RCT Entities:
BACKGROUND: Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS). METHODS:Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300. FINDINGS: Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour <1 cm) was achieved in 37% (55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum albumin ≤2·5, CA125 > 2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS. INTERPRETATION: The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied. FUNDING: Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan. CLINICAL TRIAL INFORMATION: UMIN000000523.
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