KEY TAKEAWAYS
- The phase 3 trial reported surgery outcomes from RATIONALE-315 investigating perioperative tislelizumab with neoadjuvant CT in NSCLC patients.
- The primary endpoints were MPR (reported previously) and event-free survival (EFS).
- The results showed that perioperative TIS with neoadjuvant CT maintained surgical feasibility, improved pathologic response, and ensured safety.
RATIONALE-315 evaluated perioperative tislelizumab (TIS) or placebo (PBO) alongside neoadjuvant chemotherapy (CT) in resectable non small cell lung cancer (NSCLC).
Dongsheng Yue and the team conducted a study that aimed to report key surgery outcomes and assess safety in RATIONALE-315 with perioperative tislelizumab and neoadjuvant chemotherapy.
Patients with treatment-naïve resectable stage II-IIIA NSCLC, ECOG PS ≤1, and no known EGFR mutations or ALK gene translocations were enrolled. They were randomized (1:1) to receive either 3-4 cycles of TIS 200 mg or PBO intravenously every 3 weeks, along with chemotherapy. This was followed by surgery and up to 8 cycles of adjuvant TIS 400 mg or PBO intravenously every 6 weeks.
The primary endpoints, as previously reported, were major pathological response (MPR) and event-free survival (EFS). The key secondary endpoint was the pathological complete response (pCR) rate. Surgery outcomes were considered exploratory endpoints.
About 453 patients were enrolled, with similar baseline characteristics between arms. Definitive surgery was undergone by 84.1% in the TIS arm and 76.2% in the PBO arm (Table). Primary reasons for surgery cancellation were patient withdrawal (20 vs 28), progressive disease (6 vs 17), and adverse events (AEs) (6 vs 2), respectively.
Surgery delays occurred in 16.3% vs 12.7% of patients, primarily due to AEs in 6.3% vs 3.5% in TIS vs PBO arms, mostly within 2 weeks. R0 resection was achieved in 95.3% vs 93.1% of patients in TIS vs PBO arm. Median duration of surgery (2.7 vs 2.8 hours) and length of hospitalization (7 vs 7 days) were similar between arms.
Any-grade AEs and grade ≥3 post-operative complication rates were 63.7% vs 61.3%, and 11.1% vs 15.6% in TIS vs PBO arms, respectively and 90-day post-surgery mortality was 1.3% vs 1.8% in TIS vs PBO arms, respectively.
The combination of perioperative TIS and neoadjuvant CT did not affect the feasibility or completeness of surgery. This led to significant improvements in MPR and pCR, with manageable safety profiles, suggesting TIS as a viable perioperative treatment for resectable NSCLC patients.
The trial was sponsored by BeiGene.
Source: https://cslide.ctimeetingtech.com/elcc24hybrid/attendee/confcal/show/session/7
Clinical Trial: https://clinicaltrials.gov/study/NCT04379635
Yue D, Tan L, Xu S, et al. (2024) “Surgical outcomes from RATIONALE-315: Randomized, double-blind, phase III study of perioperative tislelizumab with neoadjuvant chemotherapy in resectable NSCLC.” Presented at ELCC 2024 (ID 9).
