Dr Cappuzzo on Findings from the RATIONALE-315 Trial in Resectable NSCLC

Federico Cappuzzo, MD, director, Oncology and Hematology Department, Azienda Unità Sanitaria Locale della Romagna-Ravenna, discusses findings from the phase 3 RATIONALE-315 trial (NCT04379635) in patients with resectable non–small cell lung cancer (NSCLC).

The RATIONALE-315 study is investigating treatment with neoadjuvant tislelizumab (BGB-A317) plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab in patients with NSCLC. Data from the trial were presented at the February ESMO Virtual Plenary. At a median follow-up of 22.0 months (range, 0.1-38.4), the HR for event-free survival (EFS) between the tislelizumab and placebo groups was 0.56 (95% CI, 0.40-0.79; P = .0003), indicating an EFS benefit with perioperative tislelizumab. Notably, the median EFS by blinded independent central review was not reached in either arm (tislelizumab arm, 95% CI, not evaluable [NE]-NE; placebo arm, 95% CI, 16.6-NE).

The 12-month EFS rates were 80.0% and 68.1% for tislelizumab and placebo, respectively, and at 24 months, the EFS rates were 68.3% and 51.8%, respectively. Furthermore, a clinically meaningful enhancement in investigator-assessed EFS was observed with tislelizumab vs placebo, with an HR of 0.55 (95% CI, 0.39-0.77). Similarly, a trend indicated an overall survival (OS) benefit with perioperative tislelizumab over placebo.

Cappuzzo begins by stating that the RATIONALE-315 trial compared neoadjuvant chemoimmunotherapy with standard platinum-based chemotherapy. This trial was designed for patients with NSCLC regardless of histology, encompassing stages II to IIIa A, he states. However, upon examining the characteristics of enrolled patients, it becomes apparent that most had squamous histology, and all participants were from Asia.

Cappuzzo finds the results from this trial impressive, particularly the pathological complete response rate. Additionally, the EFS and OS data favored treatment with neoadjuvant chemoimmunotherapy over placebo. This benefit extended across all patient subgroups and was seen irrespective of PD-L1 expression levels, indicating that the advantage with tislelizumab was not driven solely by PD-L1 overexpression, he says. Notably, patients with lower PD-L1 expression levels derived the most benefit from tislelizumab in the trial, Cappuzzo concludes.