Tanzawa Shigeru, Ushijima Sunao, Shibata Kazuhiko, Shibayama Takuo, Bessho Akihiro, Kaira Kyoichi, Misumi Toshihiro, Shiraishi Kenshiro, Matsutani Noriyuki, Tanaka Hisashi, Inaba Megumi, Haruyama Terunobu, Nakamura Junya, Kishikawa Takayuki, Nakashima Masanao, Iwasa Keiichi, Fujiwara Keiichi, Kohyama Tadashi, Kuyama Shoichi, Miyazawa Naoki, Nakamura Tomomi, Miyawaki Hiroshi, Ishida Hiroo, Oda Naohiro, Ishikawa Nobuhisa, Morinaga Ryotaro, Kusaka Kei, Fujimoto Nobukazu, Yokoyama Toshihide, Gemba Kenichi, Tsuda Takeshi, Nakagawa Hideyuki, Ono Hirotaka, Shimizu Tetsuo, Nakamura Morio, Kusumoto Sojiro, Hayashi Ryuji, Shirasaki Hiroki, Ochi Nobuaki, Aoe Keisuke, Kanaji Nobuhiro, Kashiwabara Kosuke, Inoue Hiroshi, Seki Nobuhiko
Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-City, Tokyo, Japan.
Department of Medical Oncology, Kumamoto Chuo Hospital, Kumamoto-City, Kumamoto, Japan.
Ther Adv Med Oncol. 2021 Feb 27;13:1758835921998588. doi: 10.1177/1758835921998588. eCollection 2021.
Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study.
In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate.
Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab.
Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.
基于 PACIFIC 研究结果，放化疗后使用度伐利尤单抗进行 1 年巩固治疗已成为不可切除的局部晚期非小细胞肺癌（LA-NSCLC）的标准治疗方案。然而，该设计中未预见的一些问题仍可进行探索，包括放化疗开始后的无进展生存期（PFS）和总生存期（OS）、接受度伐利尤单抗巩固治疗的患者比例以及最佳化疗方案。在日本，S-1 + 顺铂（SP）联合方案在多项临床研究结果显示其疗效和耐受性具有良好平衡，因此在临床实践中经常被选用。然而，采用该 SP 方案后进行度伐利尤单抗巩固治疗的疗效和安全性尚未得到评估。因此，我们计划开展一项多中心、前瞻性、单臂、II 期研究。
在未经治疗的 LA-NSCLC 患者中，每 4 周进行一个周期的 S-1（80 - 120mg/体表面积，第 1 - 14 天）+ 顺铂（60mg/m²，第 1 天）联合化疗，同时进行胸部放疗（60Gy），共两个周期。缓解者随后每 2 周接受度伐利尤单抗治疗，持续 1 年。主要终点为 1 年 PFS 率。
与日本传统标准方案相比，SP 方案预计可降低肺炎、食管炎和发热性中性粒细胞减少症的发生率，这些并发症会使度伐利尤单抗巩固治疗的起始变得复杂，并且在放化疗期间具有更高的抗肿瘤疗效。因此，预计更多患者在基于 SP 的放化疗后能够成功接受度伐利尤单抗巩固治疗，从而延长 PFS 和 OS。本研究中 SP 方案的毒性和疗效结果也将为未来放化疗与度伐利尤单抗联合应用的确立提供重要信息。
日本临床试验注册中心，jRCTs031190127，于 2019 年 11 月 1 日注册，https://jrct.niph.go.jp/latest-detail/jRCTs031190127。
