Kenjiro Namikawa1, Yoshio Kiyohara2, Tatsuya Takenouchi3, Hisashi Uhara4, Hiroshi Uchi5, Shusuke Yoshikawa6, Sumiko Takatsuka7, Hiroshi Koga8, Naoko Wada9, Hironobu Minami10, Masahiro Hatsumichi11, Suguru Asada12, Yoshinobu Namba13, Naoya Yamazaki14. 1. Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: knamikaw@ncc.go.jp. 2. Dermatology Division, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: y.kiyohara@scchr.jp. 3. Department of Dermatology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Niigata 961-8566, Japan. Electronic address: tatsuya@niigata-cc.jp. 4. Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. Electronic address: uharah@sapmed.ac.jp. 5. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: uchihir@dermatol.med.kyushu-u.ac.jp. 6. Dermatology Division, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: s.yoshikawa@scchr.jp. 7. Department of Dermatology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Niigata 961-8566, Japan. Electronic address: sumiko-ta@niigata-cc.jp. 8. Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. Electronic address: koga@shinshu-u.ac.jp. 9. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: w-naoco@med.kyushu-u.ac.jp. 10. Department Medical Oncology/Hematology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. Electronic address: hminami@med.kobe-u.ac.jp. 11. Ono Pharmaceutical Co. Ltd., 1-8-2 Kyutaromachi, Chuo-ku, Osaka 541-8564, Japan. Electronic address: hatsumichi@ono.co.jp. 12. Ono Pharmaceutical Co. Ltd., 1-8-2 Kyutaromachi, Chuo-ku, Osaka 541-8564, Japan. Electronic address: s.asada@ono.co.jp. 13. Ono Pharmaceutical Co. Ltd., 1-8-2 Kyutaromachi, Chuo-ku, Osaka 541-8564, Japan. Electronic address: y.nanba@ono.co.jp. 14. Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: nyamazak@ncc.go.jp.
Abstract
AIM: The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naïve Japanese patients with advanced melanoma. METHODS: In this multicentre, single-arm study, treatment-naïve Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. RESULTS: The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2-27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III-IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naïve Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III-IV AEs were high but manageable with appropriate medical attention and treatment. TRIAL REGISTRATION: JapicCTI-152869.
AIM: The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naïve Japanese patients with advanced melanoma. METHODS: In this multicentre, single-arm study, treatment-naïve Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. RESULTS: The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2-27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III-IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naïve Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III-IV AEs were high but manageable with appropriate medical attention and treatment. TRIAL REGISTRATION: JapicCTI-152869.