The benefit of neoadjuvant immunotherapy and chemotherapy in resectable NSCLC indicated that this combination therapy may provide more surgical opportunities and survival benefits to potentially resectable locally advanced NSCLC. Herein, we initiated a phase II study to evaluate the feasibility of immunotherapy plus chemotherapy in stage IIIA/IIIB NSCLC.
We planned to recruit 33 patients (pts) with stage IIIA/IIIB EGFR/ALK/ROS wild-type NSCLC. Eligible pts received 2 cycles of neoadjuvant chemoimmunotherapy (PD-1 inhibitor TIS, nab-paclitaxel, and cisplatin/carboplatin) and were reassessed for surgery. Thereafter, pts underwent surgery within 6 weeks and continued 2 cycles of TIS plus chemotherapy, followed by up to 15 cycles of TIS monotherapy. The primary endpoint was the R0 resection rate. Secondary endpoints were major pathologic response (MPR), pathologic complete response (pCR), disease-free survival, and overall survival.
From Jan 2021 to Sep 2022, 18 of 33 enrolled pts (54.5%) completed neoadjuvant therapy and underwent resection (13 with IIIA and 5 with IIIB disease). No treatment-related surgical delay occurred. 17 of 18 pts (94.4%) underwent successful R0 resection (Table). Of 18 pts who underwent resection,6 (33.3%) achieved pCR and 4 (22.2%) achieved MPR, resulting in an overall pathologic response rate of 55.6%. Of the 4 pts who achieved MPR, 3 had only 1% viable tumor cells in the resection specimen. The overall response rate (ORR) and disease control rate (DCR) were 88.9% (16/18) and 100 % (18/18), respectively. Both the clinical and pathological downstaging occurred in 16 of 18 pts (88.9%).
Outcomes Results, n (%, 95%CI); n = 18 Radiological response PR 16 (88.9, 65.29-98.62) SD 2 (11.1, 1.38-34.71) ORR 16 (88.9, 65.29-98.62) DCR 18 (100, 81.5-100.0) Surgical resection R0 17 (94.4, 72.71-99.86) R1 1 (5.6, 0.14-27.29) Downstaging rate clinical 16 (88.9, 65.29-98.62) pathologic 16 (88.9, 65.29-98.62) Pathologic response 10 (55.6, 30.76-78.47) MPR 4 (22.2, 6.41-47.64) pCR 6 (33.3, 13.34-59.01)
Neoadjuvant TIS plus chemotherapy increased surgical opportunities in potentially resectable locally advanced stage IIIA/IIIB NSCLC. The encouraging R0 resection rate observed in this study supports further investigation.
NCT04865705.
Chunlu Shu from Medical Affairs, BeiGene, Ltd.
Qinghua Zhou and Yongsheng Wang.
BeiGene Ltd.
All authors have declared no conflicts of interest.