Thrombotic events and mortality associated with bispecific antibodies in lung cancer: A systematic review.

Abstract

e15101 Background: Bispecific antibodies have emerged as a promising therapeutic option in lung cancer. Despite their therapeutic potential, concerns about thrombotic side effects, including pulmonary embolism (PE) and deep vein thrombosis (DVT), remain significant in this patient population. This systematic review aimed to evaluate the incidence and characteristics of thrombotic events in patients with lung cancer treated with bispecific antibodies. Methods: Following PRISMA guidelines, a comprehensive literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov using relevant MeSH terms and keywords. Five original articles reporting bispecific antibodies thrombotic adverse effects in lung cancer were included. The included studies were reviewed and summarized to provide a comprehensive understanding of thrombotic complications in this patient population. Results: We included 910 patients from five studies (Phase 1-3), with a median age of 62 years (25–88), and 47 % were male. 99% of patients had ECOG status 0-1. Median follow-up was 13.3 months (0.1-31). Amivantamab (EGFR + MET) and tarlatamab (Delta-like ligand 3 x CD3) were used in 80% and 20% of cases for advanced non–small cell lung cancer (NSCLC) and extensive stage small-cell lung cancer, respectively. Additional therapies included lazertinib (60%), carboplatin/pemetrexed (20%), and no therapy in (20%) cases. Thrombotic events were reported in 222 (24%) patients, accounting for a significant proportion of adverse events. PE was the most frequent thrombotic complication reported in 94 patients (10%), of which 4 (4.4%) were classified as Grade 3 and higher. DVT was reported in 61 patients (7%). The study by Cho et al., reported the largest cohort (n = 429) of EGFR-mutated NSCLC patients treated with Amivantamab. This study reported incidence of various thrombotic events beyond PE and DVT, which included thrombophlebitis (6 cases, 1%), jugular vein thrombosis (3 cases, 1%), portal vein thrombosis, sigmoid sinus thrombosis, and superior sagittal sinus thrombosis (each 1 case, < 1%). All-cause mortality was 8% and, disease progression (20 cases, 2.2%) was the most common cause of mortality while thrombosis-related mortality occurred in 2 patients ( < 1%). Conclusions: Thrombotic events and all-cause mortality are significant concerns in patients receiving bispecific antibodies in lung cancer. While these findings highlight the need for vigilance, further studies with larger cohorts and long-term follow-up are essential to better understand the safety profile.