Impact of maintenance pemetrexed cessation on clinical outcomes of patients with metastatic non-squamous NSCLC.

8568 Background: Combination chemoimmunotherapy including pemetrexed and a PD(L)1 inhibitor is a common first line systemic approach for patients with metastatic non-squamous non-small cell lung cancer (NSCLC). Patients often discontinue maintenance pemetrexed due to adverse effects, and little is known about the impact of maintenance pemetrexed cessation on progression free survival (PFS) and overall survival (OS). Methods: 121 patients with stage IV or recurrent, metastatic non-squamous NSCLC treated at VUMC were included in this retrospective analysis. Patients diagnosed between 7/2017- 9/2023 were included if they received maintenance pemetrexed and pembrolizumab. Patients were divided into two groups: those who stopped pemetrexed due to toxicity and those who did not. PFS and OS were measured from time of stage IV or metastatic diagnosis to the date of radiographic progression or death, respectively, and compared with the Kaplan Meier method. Results: Among patients with stage IV or recurrent, metastatic NSCLC (n = 121), who remained on maintenance pemetrexed and pembrolizumab (n=68), the median PFS was 11.7 months (95% CI, 7.47-NA) compared to 24.3 months (95% CI, 19.4-NA) among patients who stopped maintenance pemetrexed (n=53; p=0.1). The median OS in the same patient groups was 25.8 months (95% CI, 13.8-NA) compared to 36.4 months (95% CI, 26.9-NA) (p=0.15), respectively. Among patients with stage IV disease at diagnosis (n = 97), the median PFS among patients who did not stop pemetrexed was 8.7 months (95% CI, 7.2–NA) compared to 24.3 months (95% CI, 17.3-NA) for patients who stopped pemetrexed (p=0.089). The median OS in these groups were 21 months (95% CI, 13.6-NA) and 38.6 months (95%, 28.0-NA) (p=0.054), respectively. Conclusions: In this study of patients with metastatic non-squamous NSCLC who received maintenance pemetrexed and pembrolizumab, patients who stopped pemetrexed due to toxicity experienced similar outcomes to those who continued with pemetrexed. The necessity of continuation of maintenance chemotherapy should be further evaluated in the immunotherapy era. [Table: see text]