Tislelizumab Plus Chemotherapy Improves Survival in Small Cell Lung Cancer

Illustration of small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com

Combination therapy with the anti-PD-1 monoclonal antibody tislelizumab (Tevimbra) and chemotherapy delivered statistically significant improvements over placebo as a first-line treatment option for patients with extensive-stage small cell lung cancer (ES-SCLC), according to data from the phase 3 RATIONALE-312 study (NCT04005716).

Of 457 patients enrolled between July 2019 and April 2021, 227 patients were randomized to receive tislelizumab plus chemotherapy and 230 patients to receive placebo plus chemotherapy. With a median follow-up of 14.2 months (IQR, 8.6-25.3), the hazard ratio for overall survival (OS) was 0.75 (95% CI, 0.61-0.93; 1-sided P =.0040), showing a statistically significant improvement with tislelizumab over placebo. The median OS was 15.5 months (95% CI, 13.5-17.1) in the tislelizumab arm vs 13.5 months (95% CI, 12.1-14.9) in the placebo arm.

The median progression-free survival (PFS) was 4.7 months (95% CI, 4.3-5.5) in the tislelizumab arm vs 4.3 months (95% CI, 4.2-4.4) in the placebo arm (HR, 0.64; 95% CI, 0.52-0.78; P <.0001). The estimated 6- and 12-month PFS rates were 35% and 21% in the tislelizumab arm vs 18% and 5% in the placebo arm.

The confirmed overall response rate was 68% (95% CI, 62%-74%) in the tislelizumab arm compared with 62% (95% CI, 55%-68%) in the placebo arm, and the median duration of response was 4.3 months (95% CI, 4.1-5.6) and 3.7 months (95% CI, 3.0-4.1) in the tislelizumab and placebo arms, respectively.

“As of the data cutoff, the OS data represent a robust analysis with greater maturity, exhibited by a longer follow-up (minimum 23.9 months), and a higher event-to-patient ratio (78%) than in the previous phase 3 trials reporting OS benefit with the addition of anti–PD-(L)1 treatment to chemotherapy in ES-SCLC, acknowledging the caveat of cross-study comparison. Long-lasting treatment benefit was observed in RATIONALE-312 throughout the study follow-up time, as reflected by the higher 2-year survival probability estimated for tislelizumab plus chemotherapy over placebo plus chemotherapy,” study authors wrote in findings published in the Journal of Thoracic Oncology.

Regarding safety, 86% of patients in each treatment arm experienced grade 3 or greater treatment-related adverse events (TRAEs), most of which were hematologic. In the tislelizumab arm, 56% (n = 127) of patients experienced neutropenia and 24% (n = 54) experienced decreased white blood cell count. In the placebo arm, 55% (n = 125) and 27% (n = 63) had decreased white blood cell counts, respectively.

“Tislelizumab plus chemotherapy is well-tolerated with a manageable safety profile, as approximately one-fifth of the patients received tislelizumab for more than 1 year, whereas few patients discontinued study treatment because of TRAEs,” study authors wrote. “The safety profile observed with tislelizumab plus chemotherapy was in line with that reported for anti-PD-1/PD-L1 therapies in combination with chemotherapy in ES-SCLC.”

REFERENCE:

Cheng Y, Fan Y, Zhao Y, et al. Tislelizumab plus platinum and etoposide versus placebo plus platinum and etoposide as first-line treatment for extensive-stage SCLC (RATIONALE-312): a multicenter, double-blind, placebo-controlled, randomized, phase 3 clinical trial. J Thorac Oncol. Published online March 7, 2024. doi:10.1016/j.jtho.2024.03.008