Crespi Veronica, Delcuratolo Marco Donatello, Minuti Gabriele, Montrone Michele, Pilotto Sara, Roca Elisa, Metro Giulio, Leonetti Alessandro, Pelizzari Giacomo, Genova Carlo, Olmetto Emanuela, Cortinovis Diego, Russo Alessandro, Pasello Giulia, Bulotta Alessandra, Grossi Francesco, Buosi Roberta, Conte Alessandro Del, Sini Claudio, Greco Carlo, Morabito Alessandro, Pignataro Daniele, Pagano Maria, Gori Stefania, Giannarelli Diana, Novello Silvia, Passiglia Francesco
Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, TO, Italy; Medical Oncology Division, ASST dei Sette Laghi, Varese, Italy.
Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, TO, Italy; Medical Oncology Unit, Foundation IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Lung Cancer. 2025 Jun;204:108576. doi: 10.1016/j.lungcan.2025.108576. Epub 2025 May 3.
The PACIFIC trial established chemoradiation followed by 1-year durvalumab consolidation as standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). This study aims to investigate therapeutic strategies and clinical outcomes after durvalumab failure in the real-world.
Patients with stage III LA-NSCLC from 23 Italian centres were retrospectively enrolled at durvalumab progression. Subsequent treatments (Sub-Tx) were prospectively collected and classified as follows:chemo-immunotherapy (subgroup-1), platinum-based chemotherapy (subgroup-2), non-platinum-based chemotherapy (subgroup-3), and targeted therapy (subgroup-4). Durvalumab progression free survival (Dur-PFS) and overall survival (Dur-OS), as well as outcomes of Sub-Tx (Sub-PFS and Sub-OS) were estimated by using the Kaplan-Meier approach.
A total of 122 patients were enrolled. Median Dur-PFS was 9.3 months (95 % CI: 7.1 - 11.4) and median Dur-OS 24.2 months (95 % CI: 18.7 - 29.7). Out of 93 patients receiving a Sub-Tx, 21.5 %, 43.0 %, 28.0 %, and 7.5 % were in the subgroup 1, 2, 3, and 4, respectively. Median Sub-PFS were 12.0, 4.1, 2.7, and 6.0 months, respectively. Patients who completed 12 months of durvalumab were 65.0 %, 27.5 %, 19.2 %, and 42.9 % across the four subgroups. In univariate analysis, the duration of durvalumab therapy was an independent factor for selecting Sub-Tx (p < 0.007). Median time to next treatment (TTNT) was 6.7 months with chemo-immunotherapy and 2.1 with chemotherapy (p = 0.009). Out of 15 patients with a TTNT > 1 year, 40 % were rechallenged with immunotherapy.
Platinum-based chemotherapy was the predominant treatment after durvalumab consolidation. Immunotherapy rechallenge was associated with the best survival outcome in selected cases, warranting further investigation.
PACIFIC试验确立了同步放化疗后使用1年度伐利尤单抗巩固治疗作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。本研究旨在探讨现实世界中在度伐利尤单抗治疗失败后的治疗策略和临床结局。
对来自23个意大利中心的III期LA-NSCLC患者在度伐利尤单抗治疗进展时进行回顾性入组。前瞻性收集后续治疗（Sub-Tx）并分类如下：化疗免疫治疗（亚组1）、铂类化疗（亚组2）、非铂类化疗（亚组3）和靶向治疗（亚组4）。采用Kaplan-Meier法评估度伐利尤单抗无进展生存期（Dur-PFS）和总生存期（Dur-OS），以及后续治疗的结局（Sub-PFS和Sub-OS）。
共入组122例患者。中位Dur-PFS为9.3个月（95%CI：7.1 - 11.4），中位Dur-OS为24.2个月（95%CI：18.7 - 29.7）。在93例接受后续治疗的患者中，分别有21.5%、43.0%、28.0%和7.5%属于亚组1、2、3和4。亚组的中位Sub-PFS分别为12.0、4.1、2.7和6.0个月。在四个亚组中，完成12个月度伐利尤单抗治疗的患者分别为65.0%、27.5%、19.2%和42.9%。单因素分析中，度伐利尤单抗治疗持续时间是选择后续治疗的独立因素（p < 0.007）。化疗免疫治疗的下次治疗中位时间（TTNT）为6.7个月，化疗为2.1个月（p = 0.009）。在15例TTNT > 1年的患者中，40%再次接受免疫治疗。
铂类化疗是度伐利尤单抗巩固治疗后的主要治疗方式。在部分病例中，再次使用免疫治疗与最佳生存结局相关，值得进一步研究。
