Tislelizumab, an anti-PD-1 antibody, was specifically engineered to minimize FcɣR macrophages binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC).
In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2:1) to receive either Arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3W) or Arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary endpoint was progression-free response (PFS) assessed by an independent review committee; clinical response and safety/tolerability were secondary endpoints.
Overall, 332 patients (n=222 [A]; n=110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 months; HR=0.645 [95% CI: 0.462, 0.902]; P=0.0044). Additionally, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the majority of reported AEs were grade 1-2 in severity. The most common grade ≥3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]).
Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.

Copyright © 2021. Published by Elsevier Inc.