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Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial
Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non–small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti–PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation.
A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function.
与单纯化疗相比，新辅助化学免疫疗法可提高可切除非小细胞肺癌（NSCLC）患者的病理完全缓解率和无事件生存率。NeoCOAST是第一个以主要病理缓解（MPR）率为主要终点，旨在为可切除NSCLC患者研究新型新辅助免疫肿瘤学联合治疗的随机多药平台试验。83名患者接受了单个周期治疗：26名患者接受度伐利尤单抗（抗PD-L1）单药治疗，21名患者接受度伐利尤单抗联合oleclumab（抗CD73）治疗，20名患者接受度伐利尤单抗联合monalizumab（抗NKG2A）治疗，16名患者接受度伐利尤单抗联合danvatiersen（抗STAT3反义寡核苷酸）治疗。与度伐利尤单抗单药治疗相比，联合治疗组患者的MPR率更高。联合治疗的安全性与度伐利尤单抗单药治疗相似。多平台免疫分析表明，度伐利尤单抗联合oleclumab以及度伐利尤单抗联合monalizumab，可增强效应免疫细胞对肿瘤的浸润、干扰素反应和三级淋巴结构形成标志物，并激活全身功能性免疫细胞，从而可提高MPR率。
新辅助平台试验可以使用MPR等候选替代终点快速生成临床和转化数据。在 NeoCOAST 中，针对可切除的NSCLC患者，与度伐利尤单抗单药治疗相比，使用度伐利尤单抗联合oleclumab或monalizumab后的MPR率有所提高，并且肿瘤转录组学特征表明免疫细胞活化和功能增强。
Cascone T, Kar G, Spicer JD, Garcia-Campelo R, Weder W, Daniel DB, Spigel DR, Hussein M, Mazieres J, Oliveira J, Yau EH, Spira AI, Anagnostou V, Mager R, Hamid O, Cheng LY, Zheng Y, Blando J, Tan TH, Surace M, Rodriguez-Canales J, Gopalakrishnan V, Sellman BR, Grenga I, Soo-Hoo Y, Kumar R, McGrath L, Forde PM. Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase 2 NeoCOAST Platform Trial. Cancer Discov. 2023 Sep 14. doi: 10.1158/2159-8290.CD-23-0436. （IF: Cancer Discov. 28.2）
Tina Cascone, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Cente
Patrick M. Forde, Bloomberg– Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University |
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