在日本进行的一项关于S-1和顺铂同步胸部放疗后使用度伐利尤单抗治疗不可切除的局部晚期非小细胞肺癌的II期试验（SAMURAI研究）的中期分析中，对阻碍启动度伐利尤单抗治疗的因素进行前瞻性分析。
Prospective analysis of factors precluding the initiation of durvalumab from an interim analysis of a phase II trial of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small cell lung cancer in Japan (SAMURAI study).
作者信息
Tanzawa Shigeru, Makiguchi Tomonori, Tasaka Sadatomo, Inaba Megumi, Ochiai Ryosuke, Nakamura Junya, Inoue Koji, Kishikawa Takayuki, Nakashima Masanao, Fujiwara Keiichi, Kohyama Tadashi, Ishida Hiroo, Kuyama Shoichi, Miyazawa Naoki, Nakamura Tomomi, Miyawaki Hiroshi, Oda Naohiro, Ishikawa Nobuhisa, Morinaga Ryotaro, Kusaka Kei, Miyamoto Yosuke, Yokoyama Toshihide, Matsumoto Chiaki, Tsuda Takeshi, Ushijima Sunao, Shibata Kazuhiko, Shibayama Takuo, Bessho Akihiro, Kaira Kyoichi, Misumi Toshihiro, Shiraishi Kenshiro, Matsutani Noriyuki, Seki Nobuhiko
机构信息
Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
出版信息
Ther Adv Med Oncol. 2022 Jul 29;14:17588359221116603. doi: 10.1177/17588359221116603. eCollection 2022.
BACKGROUND
The standard of care for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC trial. Disease progression and pneumonitis were reported as the main reasons to preclude the initiation of durvalumab in multiple retrospective studies. However, the transition rate and the reasons for failure to proceed to consolidation therapy with durvalumab after CRT were not evaluated prospectively. Although phase II studies in Japan have shown high efficacy and tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has yet been reported. We therefore conducted a phase II study to verify the efficacy and safety of durvalumab following SP-based CRT. In this interim analysis, we report the transition rate and the reasons for its failure.
METHODS
In treatment-naïve LA-NSCLC, cisplatin (60 mg/m, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab every 2 weeks for up to 12 months. The primary endpoint was 12 month progression-free survival rate.
RESULTS
Fifty-nine patients were enrolled, of whom 86.4% (51/59) proceeded to durvalumab. All of them initiated durvalumab within 42 days after CRT [median 18 days (range: 3-38)], including 27.5% (14/51) in <14 days. Common reasons for failure to proceed to durvalumab were disease progression (2/59, 3.4%) and adverse events (6/59, 10.2%). Among the latter cases, four resumed treatment and proceeded to durvalumab within 42 days on off-protocol. The objective response rate and the disease control rate were 62.7% and 93.2%, respectively. The incidences of ⩾grade 3 pneumonitis, febrile neutropenia, and esophagitis were 0%, 8.5%, and 3.4%, respectively.
CONCLUSION
Regarding durvalumab after CRT, this interim analysis of the SAMURAI study clarified the high transition rate, early introduction, and reasons for failure to proceed to consolidation therapy, which were not determined in the PACIFIC trial.
TRIAL REGISTRATION
Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.
背景
基于 PACIFIC 试验，不可切除的局部晚期非小细胞肺癌（LA-NSCLC）的标准治疗方案是放化疗（CRT）后使用度伐利尤单抗。在多项回顾性研究中，疾病进展和肺炎被报告为妨碍启动度伐利尤单抗治疗的主要原因。然而，CRT 后接受度伐利尤单抗巩固治疗的转换率以及未能进行该治疗的原因尚未进行前瞻性评估。尽管日本的 II 期研究显示顺铂+S-1（SP）方案的 CRT 具有高疗效和耐受性，但尚未有关于基于 SP 的 CRT 后使用度伐利尤单抗的前瞻性研究报告。因此，我们开展了一项 II 期研究，以验证基于 SP 的 CRT 后度伐利尤单抗的疗效和安全性。在本次中期分析中，我们报告了转换率及其未成功的原因。
方法
在未经治疗的 LA-NSCLC 患者中，给予顺铂（60mg/m²，第 1 天）和 S-1（80-120mg/体，第 1-14 天），每 4 周为 1 个周期，共 2 个周期，同时进行胸部放疗（60Gy），随后每 2 周给予度伐利尤单抗，持续 12 个月。主要终点为 12 个月无进展生存率。
结果
共纳入 59 例患者，其中 86.4%（51/59）接受了度伐利尤单抗治疗。所有患者均在 CRT 后 42 天内开始使用度伐利尤单抗[中位时间 18 天（范围：3-38 天）]，其中 27.5%（14/51）在<14 天内开始使用。未进行度伐利尤单抗治疗的常见原因是疾病进展（2/59，3.4%）和不良事件（6/59，10.2%）。在后一种情况中，4 例患者恢复治疗并在 42 天内按照非方案治疗继续使用度伐利尤单抗。客观缓解率和疾病控制率分别为 62.7%和 93.2%。≥3 级肺炎、发热性中性粒细胞减少症和食管炎的发生率分别为 0%、8.5%和 3.4%。
结论
关于 CRT 后使用度伐利尤单抗，SAMURAI 研究的本次中期分析明确了高转换率、早期启用以及未能进行巩固治疗的原因，这些在 PACIFIC 试验中未明确。
试验注册
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。
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