Activity Of Pemetrexed In Patients With Driver Oncogene Positive Non-Small Cell Lung Cancer And Squamous Histology.

Abstract Pemetrexed, a multi-targeted antifolate chemotherapy agent, has been used both as a single agent chemotherapy as well as in combination given its favorable side effect profile, and has been the only effective continuation maintenance chemotherapy regimen after initial doublet use associated with increased overall survival (OS) among non-squamous non-small cell lung cancers. The current labelled indications for pemetrexed in NSCLC are restricted to those with non-squamous histology due to previous studies that showed worse outcomes in patients with squamous histology when compared to non-squamous histology. More recently, however, in the era of increased molecular profiling of NSCLC, it has been observed that patients with ALK, ROS1, and RET gene fusions have demonstrated marked sensitivity to pemetrexed. This retrospective case series, therefore, evaluated the response to pemetrexed among a cohort of 9 oncogene-driven patients with squamous (or adenosquamous) histologies who did receive pemetrexed based chemotherapy. Response rates, progression free survival (PFS), and OS for these patients were compared to a historical group of patients published in previous studies that examined pemetrexed response. The results indicated a positive response to pemetrexed in patients with an actionable driver oncogene occurring in the context of squamous or adenosquamous histology. Patients in the oncogene-driven adenosquamous/squamous group had significantly higher response rates as compared to the historical squamous cell group and no significant difference in response rates as compared to the historical adenocarcinoma comparison group. In summary, contrary to prior studies, this case series does suggest that pemetrexed may be a viable treatment option in patients with squamous cell histology who also have a targetable mutation. Citation Format: Yunan Nie, Tejas Patil, David Ross Camidge. Activity of pemetrexed in patients with driver oncogene positive non-small cell lung cancer and squamous histology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1375.