Clinical evidence and adverse event management update of patients with RET- rearranged advanced non-small-cell lung cancer (NSCLC) treated with pralsetinib.

Current non-small cell lung cancer (NSCLC) management relies on genome-driven precision oncology thus shifting treatment paradigm towards biomarker-guided tumor-agnostic approaches. Recently, rearranged during transfection (RET) has been endorsed as tissue-agnostic target with sensitivity to RET inhibition. There are currently two selective RET tyrosine kinase inhibitors, pralsetinib and selpercatinib. The recent introduction of pralsetinib in the treatment algorithm of RET-rearranged tumor along with the mounting clinical evidence of pralsetinib durable activity from both randomized and observational studies holds the potential to disclose new avenues in the management of RET fusion positive NSCLC patients. Our narrative review aims to discuss the available clinical evidence on pralsetinib efficacy, particularly on brain metastases, and tolerability profile. In addition, our work explores the relevance of detecting RET fusions upfront in the disease history of patients with NSCLC.

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Declaration of Competing Interest CB declares honoraria from Roche, BMS, Astrazeneca; PB declares advisory role for: Seagen, Regeneron, Janssen, Roche, Pierre Fabre; speaker bureau: Amgen, MSD, BMS, AstraZeneca, Roche, Janssen, Takeda, Novartis; virtual meetings subscription: Amgen Daiichi Sankyo; institutional research grant: Roche, Pfizer; LB declares grant for scientific project from Astrazeneca, honoraria from Roche, Astrazeneca, MSD, Novartis, support for attending meetings from Roche and Astrazeneca, and advisory role from Roche, Astrazeneca, Novartis, MSD; GLR declares advisory role, travel accommodations and consultancies: MSD, BMS, Astrazeneca, Roche, Takeda, Eli Lilly, Amgen, Pfizer, Novartis, Sanofi, Gsk pi role: MSD, BMS, Astrazeneca, Roche, Pfizer, Novartis, Sanofi, Gsk; IP declares honoraria from Roche, BMS, Amgen, support for attending meetings from Roche, Sanofi, BMS, Takeda, Amgen and advisory role from Takeda, Amgen, Sanofi and Boheringer Ingelheim; AP declares consulting or advisory role for AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Jansenn, Merck Sharp & Dohme, Mundipharma, Novartis, Roche; speakers’ bureau for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, eCancer, Jansenn, Merck Sharp & Dohme, Medscape, PeerVoice, PeerView TouchONCOLOGY; MR declares consulting and/or speaker fees and/or support for attending meetings for: MSD, BMS, AstraZeneca, Roche, Janssen, Takeda, Novartis, Pfizer, Sanofy, Lilly, Amgen; AC and GM have nothing to disclose.