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Κυριακή 15 Νοεμβρίου 2020

Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG‐TR)

Alexandros G.Sfakianakis shared this article with you from Inoreader
Μέσω Cancer Science

Abstract

The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II‐IIIA non‐squamous non‐small cell lung cancer (Ns‐NSCLC). This study did not meet the primary endpoint (recurrence‐free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigate relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin‐fixed, paraffin‐embedded tumor tissues (n=389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. EGFR mutations were detected frequently in Ns‐NSCLC (139/374). Patients without any EGFR mutations experience longer RFS in the Pem/Cis arm vs Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12‐16 mut/Mb) tended to improve survival. In patients with wild type EGFR, TMB≥12 mut/Mb was significantly associated with improved RFS with Pem/Cis vs Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis vs Vnr/Cis in Ns‐NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be utilized as a predictive biomarker.

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