Abstract: Pemetrexed-based chemotherapy regimens (pem regimens) are the standard first-line treatment option in patients with non-squamous non–small cell lung cancer (NSCLC). The objective of this systematic review was to assess the efficacy of pemetrexed in the context of epidermal growth factor receptor (EGFR ) mutation-positive NSCLC following the failure of EGFR –tyrosine kinase inhibitor (TKI) treatment. We searched biomedical literature databases (PubMed, EMBASE, and the Cochrane library) and conference proceedings for studies evaluating the efficacy of pemetrexed monotherapy or pemetrexed combined with platinum or any other chemotherapeutic agent in EGFR –mutation-positive NSCLC after EGFR -TKI failure. We extracted data of primary outcomes of interest (progression-free survival [PFS], overall survival [OS], and overall response rate [ORR]). The weighted median PFS, OS, and ORR were then calculated. Of 83 potentially relevant studies, eight (three randomized studies and five retrospective studies) were identified (involving 1,193 patients) and included in this systematic review, with 640 patients receiving pem regimens. The weighted median PFS, median OS, and ORR for patients treated with pem regimens were 5.09 months, 15.91 months, and 30.19%, respectively. Our systematic review results showed a favorable efficacy profile of pem regimens in NSCLC patients with EGFR  mutation after EGFR –TKI failure.
Keywords: pemetrexed, advanced non–small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor