Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy-naive advanced melanoma.
Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy-naive advanced melanoma.
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DOI：
10.1111/1346-8138.15514
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Yamazaki N
中科院分区：
文献类型：
--
作者：
Namikawa K;Kiyohara Y;Takenouchi T;Uhara H;Uchi H;Yoshikawa S;Takatsuka S;Koga H;Wada N;Minami H;Hatsumichi M;Namba Y;Yamazaki N
在最近更新的临床实践指南中，Nivolumab + ipilimumab联合治疗是目前晚期黑色素瘤的首选方案之一。然而，关于联合治疗肢端或粘膜亚型的疗效的证据仍然不太可靠。这是一项多中心、开放标签、非对照II期研究的最终分析，该研究调查了日本晚期黑色素瘤（包括肢端或粘膜亚型）患者的长期疗效和安全性，以及研究药物停药后的后续治疗。患者每隔3周接受4次剂量的纳武单抗（1mg /kg静脉注射）联合伊匹单抗（3mg /kg静脉注射），随后每隔2周接受一次纳武单抗（3mg /kg静脉注射）。中位随访期为20.8个月（范围5.2-35.0）。中央和局部评估的客观有效率均为43.3%（13/30；95%可信区间[CI]， 25.5-62.6）。中位无进展生存期未达到（95% CI， 3.02 -未达到），中位总生存期也未达到（95% CI， 19.52 -未达到）。30个月无进展生存率和总生存率分别为50.3%和54.2%。没有发现新的安全隐患。停药后，83.3%的患者接受了某种形式的后续治疗，其中43.3%的患者接受了纳武单抗单药治疗，26.7%的患者接受了放疗。在因免疫相关不良事件而停用研究药物的4例患者中，2例接受了后续治疗（分别为纳武单抗和伊匹单抗），另外2例显示长期无治疗生存期（分别为659天和590天）。nivolumab联合ipilimumab在包括肢端和粘膜亚型的日本黑色素瘤患者中观察到长期生存率，这与CheckMate 067研究一致。许多患者在停止使用纳武单抗加伊匹单抗治疗后继续安全地接受某种形式的治疗。
Nivolumab plus ipilimumab combination is currently one of the preferred regimens for advanced melanoma in recently updated clinical practice guidelines. However, the evidence on the efficacy of the combination for acral or mucosal subtypes remains less robust. This is the final analysis of a multicenter, open‐label, uncontrolled phase II study that investigated the long‐term efficacy and safety in treatment‐naive Japanese patients with advanced melanoma, including acral or mucosal subtypes, and subsequent therapy after discontinuation of the investigational agents. Patients received four doses of nivolumab (1 mg/kg i.v.) in combination with ipilimumab (3 mg/kg i.v.) at 3‐week intervals, followed by doses of nivolumab (3 mg/kg i.v.) at 2‐week intervals. The median follow‐up period was 20.8 months (range, 5.2–35.0). The centrally and locally assessed objective response rates were both 43.3% (13/30; 95% confidence interval [CI], 25.5–62.6). Median progression‐free survival was not reached (95% CI, 3.02–not reached), and median overall survival was also not reached (95% CI, 19.52–not reached). The 30‐month progression‐free survival and overall survival rates were 50.3% and 54.2%, respectively. No new safety concerns were detected. After discontinuation of the investigational agents, 83.3% of patients received some form of subsequent therapy including 43.3% of patients who received nivolumab monotherapy and 26.7% of patients who received radiotherapy. Of the four patients who discontinued the investigational agents because of immune‐related adverse events, two received subsequent therapy (nivolumab and ipilimumab, respectively) and the other two showed long‐term treatment‐free survival (659 and 590 days, respectively). Long‐term survival with nivolumab plus ipilimumab was observed in Japanese patients with melanoma including acral and mucosal subtypes, which is consistent with the CheckMate 067 study. Many patients continued to receive some form of treatment safely after stopping treatment with nivolumab plus ipilimumab.
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DOI：
10.1056/nejmoa1709684
发表时间：
2017-10-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Wolchok JD;Chiarion-Sileni V;Gonzalez R;Rutkowski P;Grob JJ;Cowey CL;Lao CD;Wagstaff J;Schadendorf D;Ferrucci PF;Smylie M;Dummer R;Hill A;Hogg D;Haanen J;Carlino MS;Bechter O;Maio M;Marquez-Rodas I;Guidoboni M;McArthur G;Lebbé C;Ascierto PA;Long GV;Cebon J;Sosman J;Postow MA;Callahan MK;Walker D;Rollin L;Bhore R;Hodi FS;Larkin J
通讯作者：
Larkin J
影响因子：
6.2
作者：
Shoushtari, Alexander N.;Munhoz, Rodrigo R.;Kuk, Deborah;Ott, Patrick A.;Johnson, Douglas B.;Tsai, Katy K.;Rapisuwon, Suthee;Eroglu, Zeynep;Sullivan, Ryan J.;Luke, Jason J.;Gangadhar, Tara C.;Salama, April K. S.;Clark, Varina;Burias, Clare;Puzanov, Igor;Atkins, Michael B.;Algazi, Alain P.;Ribas, Antoni;Wolchok, Jedd D.;Postow, Michael A.
通讯作者：
Postow, Michael A.
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
50.5
作者：
Michielin, O.;van Akkooi, A. C. J.;Keilholz, U.
通讯作者：
Keilholz, U.
影响因子：
8.8
作者：
Hamid O;Robert C;Ribas A;Hodi FS;Walpole E;Daud A;Arance AS;Brown E;Hoeller C;Mortier L;Schachter J;Long J;Ebbinghaus S;Ibrahim N;Butler M
通讯作者：
Butler M