In patients with resectable non–small cell lung cancer (NSCLC), perioperative treatment involving the checkpoint inhibitor tislelizumab led to a statistically significant benefit in event-free survival and a favorable trend for overall survival, investigators for the phase III RATIONALE-315 trial have reported.1
“Major pathologic and complete pathologic responses were also significantly improved with neoadjuvant tislelizumab plus platinum-doublet chemotherapy,” said Dongsheng Yue, MD, of Tianjin Medical University Cancer Institute and Hospital, China, who presented the interim results for event-free survival and overall survival at the February 2024 ESMO (European Society for Medical Oncology) Virtual Plenary. Dr. Yue previously reported the results for pathologic response at the ESMO Congress 2023.2
“Taken together, the statistically and clinically significant event-free survival and major pathologic response and pathologic complete response benefits, alongside manageable safety, support the use of perioperative tislelizumab plus neoadjuvant platinum-doublet chemotherapy for patients with resectable stage II–IIIA non–small cell lung cancer,” Dr. Yue said.
RATIONALE-315 enrolled 453 patients with resectable stage II–IIIA NSCLC. Patients had squamous or nonsquamous histology, no genomic drivers, and any levels (or none) of PD-L1 expression. They were randomly assigned to receive neoadjuvant tislelizumab plus platinum-based chemotherapy or chemotherapy alone. Following surgery, the experimental group received up to eight cycles of adjuvant tislelizumab, whereas the control arm received placebo.
Multiple Endpoints Met
As previously reported, after neoadjuvant therapy and resection, the rate of major pathologic response (defined as ≤ 10% residual tumor) was 56.2% in the tislelizumab arm vs 15.0% in the chemotherapy-alone arm (P < .0001)—an improvement of 41.4% with tislelizumab. Rates of pathologic complete response (no residual tumor) were 40.7% and 5.7% (P < .0001), respectively—a 35.0% improvement.
At 22 months of median follow-up, median event-free survival in the intent-to-treat analysis by blinded independent review was not reached in either arm; at 24 months, 68.3% of the tislelizumab arm were free of events compared with 51.8% of the placebo arm (hazard ratio [HR] = 0.56; P = .0003). “A clinically meaningful improvement per investigator review was also observed,” he reported.
The event-free survival benefit with perioperative tislelizumab over placebo was generally consistent across prespecified subgroups. By PD-L1 expression, hazard ratios were 0.71 for ≥ 50% PD-L1 expression; 0.34 for PD-L1 expression between 1% and 49%; 0.50 for PD-L1 expression ≥ 1%; and 0.80 for PD-L1 expression < 1%. By histology, for squamous disease, the 24-month event-free survival rates were 70.2% with tislelizumab and 52.2% with placebo (HR = 0.56); for patients with nonsquamous tumors, these rates were 60.8% and 52.1%, respectively (HR = 0.64). Benefit was confirmed in patients with stage II and IIIA disease. The interim analysis also revealed a trend for an overall survival benefit favoring tislelizumab (HR = 0.62; P = .0193, with P = .0001 the statistical boundary), according to Dr. Yue.
The safety profile of perioperative tislelizumab plus chemotherapy was reported to be manageable and consistent with the known risks of the individual therapies. Grade ≥ 3 treatment-related adverse events were observed in 72% of the tislelizumab arm and 66% of the control arm and led to death in four and two patients, respectively.
DISCLOSURE: Dr. Yue reported no conflicts of interest.
REFERENCES
1. Yue D, et al: ESMO Virtual Plenary. Abstract VP1-2024. Presented February 15, 2024.
2. Yue D, et al: ESMO Congress 2023. Abstract LBA58. Presented October 23, 2023.
