Predictive factors for long-term responders of pemetrexed maintenance treatment in non-small cell lung cancer

Abstract

Background: We determined the clinical characteristics and predictive factors of long-term response to pemetrexed maintenance therapy as first-line treatment for non-small cell lung cancer (NSCLC). Methods: A total of 950 advanced NSCLC patients received pemetrexed (500 mg/m 2 ) plus cisplatin (60 mg/m 2 ) (Pem-Cis) induction chemotherapy every three weeks as first-line treatment between January 2010 and August 2018. Patients who did not show progression after four cycles of Pem-Cis and received at least one cycle of pemetrexed maintenance were recruited (n = 199). Results: Patients were divided into subgroups according to total cycles of pemetrexed: ≤ 10 (F10, n = 134) and > 10 (M10, n = 65). The M10 group had a higher proportion of patients with stage M1a (intrathoracic metastasis alone) and exhibited lower levels of thymidylate synthase (TS) than the F10 group (median H-score 10.0% vs. 60.0%; P = 0.031). Further subgrouping identified extreme responders: ≤ 7 (F7, n = 101) and ≥ 20 (M20, n = 26) cycles. The M20 group showed lower mean serum CEA levels before (17.5 vs. 147.0; P = 0.099) and after (6.9 vs. 53.2; P = 0.001) Pem-Cis treatment, and a higher incidence of normalization after Pem-Cis (abnormal 41.7% vs. 68.5%; P = 0.015). M1a stage, normalization of CEA levels after Pem-Cis, and lower TS H-score were predictors of progression-free survival in patients administered pemetrexed maintenance. Conclusion: M1a stage and lower TS expression were predictors of long-term response to pemetrexed maintenance. CEA normalization after Pem-Cis could be an additional surrogate marker of positive response to long-term treatment.