RATIONALE-315: Post hoc analysis of event-free survival by surgically relevant subgroups treated with perioperative tislelizumab and neoadjuvant chemotherapy vs neoadjuvant chemotherapy.

Abstract

8059 Background: RATIONALE-315 (NCT04379635) compared the efficacy and safety of perioperative tislelizumab (TIS) or placebo (PBO) + neoadjuvant chemotherapy (CT) in patients (pts) with resectable NSCLC. This post hoc analysis reports correlation of event-free survival (EFS) to key surgical outcomes. Methods: Pts with resectable stage II-IIIA NSCLC (N=453) were randomized 1:1 to 3-4 cycles of TIS 200 mg or PBO Q3W with neoadjuvant CT, followed by surgery and ≤8 cycles of adjuvant TIS 400 mg or PBO Q6W. Primary and key secondary endpoints were reported previously. Exploratory endpoints of surgical outcomes are presented here. Results: As of March 7, 2025, 190/226 pts in the TIS arm and 173/227 pts in the PBO arm underwent definitive surgery. EFS benefit with TIS vs PBO was observed in all surgically relevant subgroups (HR: 0.62; 95% CI: 0.44-0.88). Although R0 resection rates were similar between treatment arms, TIS showed greater EFS benefit vs PBO (HR: 0.62; 95% CI: 0.43-0.90). A similar trend was observed in R1/R2 pts (HR: 0.75; 95% CI: 0.19-3.05); however, data should be interpreted with caution due to small pt numbers. Pts in the TIS arm who underwent open and minimally invasive surgery (n=179) achieved improved EFS benefit compared with those in the PBO arm (n=157), regardless of disease stage and surgery type (Table). In pts who underwent minimally invasive and open surgery, respectively, grade ≥3 treatment-emergent adverse events occurred in 77.2% and 78.8% of pts in the TIS arm and 71.3% and 81.7% in the PBO arm. In pts who underwent minimally invasive surgery in the TIS arm, grade ≥3 immune mediated adverse events were reported in 11.4% of all pts (13/114), 10.4% of pts in stage II (5/48), and 12.3% in stage IIIa (8/65). Conclusions: Perioperative TIS + neoadjuvant CT improved EFS in pts with resectable NSCLC across all surgically relevant subgroups regardless of disease stage or surgery type. These results further support TIS + CT as an efficacious and safe treatment option that may reduce the burden of invasive surgical intervention. Clinical trial information: NCT04379635 . EFS rate, % (95% CI) 12 mo 24 mo 48 mo Approach to surgery, NSCLC stage TIS PBO TIS PBO TIS PBO Minimally invasive  Overall 89.7 (82.2-94.2) 79.0 (78.0-86.6) 81.0 (72.1-87.3) 63.8 (51.8-73.6) 74.3 (64.0-82.1) 55.4 (42.0-67.0)  Stage II 90.9 (82.8-99.8) 85.0 (73.7-98.0) 83.6 (73.1-95.5) 69.8 (55.8-87.4) 77.0 (64.6-91.8) 66.5 (52.1-84.8)  Stage IIIa 88.7 (77.8-94.5) 73.1 (56.7-84.1) 78.9 (66.5-87.2) 58.0 (41.3-71.4) 72.4 (58.6-82.3) 46.7 (29.0-62.6) Open  Overall 78.5 (65.9-86.9) 70.9 (57.8-80.6) 60.2 (46.7-71.2) 47.8 (34.9-59.6) 54.1 (40.4-66.0) 31.1 (17.3-45.8)  Stage II 85.7 (72.0-100) 80.0 (64.3-99.6) 76.2 (60.0-96.8) 55.0 (37.0-81.8) 71.4 (54.5-93.6) NE (NE-NE)  Stage IIIa 74.1 (57.2-85.2) 66.4 (49.9-78.6) 50.3 (33.7-64.8) 44.3 (28.9-58.6) NE (NE, NE) 28.7 (13.9-45.5) NE, not evaluable.