Carboplatin plus pemetrexed versus pemetrexed alone in advanced thymoma and thymic carcinoma: a retrospective cohort study

Introduction: Pemetrexed is approved as a single agent for advanced and metastatic thymoma and thymic carcinoma. In practice, pemetrexed is often given with carboplatin, but the safety and effectiveness of this combination has not been established in either of these rare diseases. Methods: We identified patients with unresectable, recurrent, or metastatic thymoma or thymic carcinoma who were treated with carboplatin/pemetrexed or pemetrexed alone from 2006-2024. Time to disease progression and objective response were determined retrospectively using RECIST 1.1. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated using Kaplan-Meier methodology. Results: We identified 24 patients (14 thymoma; 10 thymic carcinoma), including 8 treated with carboplatin/pemetrexed and 16 with pemetrexed alone. For our combined cohort, mPFS was not reached (NR) with carboplatin/pemetrexed vs. 14.7m with pemetrexed (p=0.27). Among patients with thymoma, mPFS with carboplatin/pemetrexed was NR vs. 15.6m for pemetrexed (p=0.09), while among patients with thymic carcinoma mPFS was 10.9m vs. 14.7m (p=0.88), respectively. At a median follow-up of 49.0m (37m for carboplatin/pemetrexed; 107m for pemetrexed), mOS was NR across all groups. The objective response rate (ORR) was 1/8 (12.5%) vs. 5/16 (31%), and the disease control rate (DCR) was 7/8 (87.5%) vs. 11/16 (69%) with carboplatin/pemetrexed and pemetrexed respectively. Discussion: Carboplatin/pemetrexed was well tolerated and not associated with statistically significant differences in PFS compared to pemetrexed monotherapy in our combined cohort or thymic carcinoma and thymoma subgroups. Carboplatin/pemetrexed demonstrated a numerically longer PFS with encouraging disease control rates particularly in patients with thymoma.