108O - Surgical outcomes from RATIONALE-315: Randomized, double-blind, phase III study of perioperative tislelizumab with neoadjuvant chemotherapy in resectable NSCLC

Background

RATIONALE-315 (NCT04379635) investigated the efficacy and safety of perioperative tislelizumab (TIS) or placebo (PBO) with neoadjuvant chemotherapy (CT) in patients (pts) with resectable NSCLC. Here, we report key surgery outcomes from the study.

Methods

Pts in China with treatment-naïve resectable stage II-IIIA NSCLC, with ECOG PS ≤1 and no known EGFR mutations or ALK gene translocations were enrolled. Pts were randomized (1:1) to 3-4 cycles of TIS 200 mg or PBO, IV Q3W, plus CT, followed by surgery and up to 8 cycles of adjuvant TIS 400 mg or PBO, IV Q6W. Primary endpoints were major pathological response (MPR, reported previously) and event-free survival. Key secondary endpoint was pathological complete response (pCR) rate. Surgery outcomes were exploratory endpoints.

Results

453 pts were enrolled and baseline characteristics were similar between arms. 190/226 pts (84.1%) in the TIS arm and 173/227 pts (76.2%) in the PBO arm underwent definitive surgery (Table). Main reasons for surgery cancellation were pt withdrawal (20 vs 28 pts), progressive disease (6 vs 17 pts) and adverse events (AEs) (6 vs 2 pts), respectively. Surgery delays occurred in 31 (16.3%) vs 22 (12.7%) pts, mainly due to AEs in 12 (6.3%) vs 6 (3.5%) pts in TIS vs PBO arms, mostly within two weeks. R0 resection was achieved in 95.3% pts in TIS vs 93.1% in PBO arm. Median duration of surgery (2.7 vs 2.8 hours) and length of hospitalization (7 vs 7 days) were similar between arms. In the TIS vs PBO arms, any-grade AEs and grade ≥3 post-operative complication rates were 63.7% vs 61.3%, and 11.1% vs 15.6%, and 90-day post-surgery mortality was 3 pts (1.3%) vs 4 pts (1.8%), respectively.

Table: 108O

Types and approaches of surgery in the RATIONALE-315 study

Data cutoff: August 21, 2023. Abbreviations: PBO, placebo; TIS, tislelizumab.

Conclusions

Perioperative TIS plus neoadjuvant CT did not impact the feasibility and completeness of surgery and was accompanied by statistically significant improvement in MPR and pCR, and manageable safety, indicating TIS is a perioperative treatment option for pts with resectable NSCLC.

Clinical trial identification

NCT04379635.

Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Yee Theng Soo, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

B. Yao, S. Wang: Financial Interests, Institutional, Full or part-time Employment: BeiGene (Beijing) Co., Ltd, Beijing, China; Financial Interests, Institutional, Stocks/Shares: BeiGene (Beijing) Co., Ltd, Beijing, China. R. Wang: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks/Shares: BeiGene. All other authors have declared no conflicts of interest.