P2.01-040 Pemetrexed plus Platinum Chemotherapy with or Without Immunotherapy in Non-Squamous NSCLC: Descriptive Safety Analysis

Pemetrexed/platinum doublet chemotherapy is under investigation in combination with various immunotherapeutic agents (atezolizumab, nivolumab, pembrolizumab) for treatment of advanced non-squamous (NS) NSCLC, with reported durable efficacy and tolerability in early-phase clinical trials. Recently, the combination of pembrolizumab plus pemetrexed/carboplatin received US FDA accelerated approval as front-line treatment for patients with this disease based on the data from a randomized phase II trial, KEYNOTE-021 Cohort G. We present our descriptive analysis of the safety outcomes of pemetrexed (combination) from 3 randomized trials (PRONOUNCE, PARAMOUNT, and KEYNOTE-021 Cohort G). Criteria for selection of studies included randomized trials, first-line treatment for NS NSCLC patients with pemetrexed-based combination treatment, with or without immunotherapy, followed by continuation maintenance (at least one arm or cohort). Parameters such as baseline characteristics, dose exposure, and safety outcomes (AE, SAE, death, dose delay or discontinuation, AE management, and hospitalization) are compared. Using data from PRONOUNCE (n=182), PARAMOUNT (n=359), and KEYNOTE-021 (Cohort G, n=123) we describe the safety outcomes of pemetrexed/platinum-based combination therapy. Median age of patients from 3 studies was 61- 66 years. The majority of patients in PRONOUNCE and PARAMOUNT were male, whereas female in KEYNOTE-021G; with ECOG PS 1, and adenocarcinoma. The number of patients who completed 4 cycles of induction were 70.8%, 67.8%, 88.1%, and 71.0% in PRONOUNCE, PARAMOUNT, and KEYNOTE 021G Combo arm and Pem+Cb only arm, with median number of treatment cycles of 6, 8, 11, 8, respectively. All pemetrexed combinations with/without immunotherapy had a reasonable and manageable safety profile in our analysis (Table 1). This analysis provides a comprehensive safety overview of pemetrexed/platinum with or without immunotherapy in NS NSCLC. Ongoing phase 3 randomized studies of the combination could further inform the safety/efficacy of pemetrexed/platinum plus immunotherapy.