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Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 524-528

Sotorasib – an inhibitor of KRAS p.G12c mutation in advanced non-small cell carcinoma: A narrative drug review

Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre, and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India

Correspondence Address:
Akhil Kapoor
Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Center, and Homi Bhabha Cancer Hospital (A Unit of Tata Memorial Center, Mumbai), Varanasi, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_145_21

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The KRAS p.G12C mutation occurs in seen in 13% of non-small cell lung cancers (NSCLCs) and in approximately 1%–3% of colorectal and other cancers. Until the last decade, there were no approved therapies for targeting the KRAS mutation, but recently, drugs targeting the mutation have been discovered. KRAS is a small protein structurally without any deep pockets making it almost impossible to target. Furthermore, it binds in its active state with the GTP protein, with remarkably close affinity making blockage of the KRAS mutation challenging. Sotorasib is a nanomolecule that selectively and irreversibly targets the KRAS mutation. The phase 2 trial (CodeBreaK100) conducted in a total of 129 patients with advanced solid tumors harboring the KRAS p.G12C mutation showed anticancer activity in patients following multiple lines of treatment. We searched for the articles published online between 2018 and May 2021 with keywords, “KRAS mutation,” “lung cancer,” and “sotorasib.” In this review article, we have discussed the history, pharmacokinetics, dosing, important studies, toxicities, and other pertinent details of sotorasib.

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