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Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and

Natalie Mausey1, Zachery Halford1

  • 1College of Pharmacy, Union University, Jackson, TN, USA.

The Annals of Pharmacotherapy
|September 13, 2023
PubMed
Abstract

Insights

Sotorasib and adagrasib show promise in treating KRAS G12C-mutated non-small cell lung cancer. Further research is needed to fully understand their safety and efficacy profiles for optimal patient care.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • KRAS mutations are common in non-small cell lung cancer (NSCLC).
  • The KRAS G12C mutation represents a targetable oncogenic driver.
  • Previously, KRAS was considered an
  • undruggable
  • target in cancer therapy.

Purpose of the Study:

  • To evaluate the safety and efficacy of sotorasib and adagrasib.
  • To assess their role in treating KRAS G12C-mutated NSCLC.

Main Methods:

  • Comprehensive literature search of PubMed and Clinicaltrials.gov (2000-2023).
  • Inclusion of prescribing information, clinical trials, and treatment guidelines.
  • Evaluation of pivotal phase I/II and phase III clinical trial data.

Main Results:

  • Sotorasib and adagrasib received accelerated FDA approval.
  • Sotorasib demonstrated an ORR of 41% and PFS of 6.3 months; phase III trial showed longer PFS vs. docetaxel (5.6 vs. 4.5 months).
  • Adagrasib showed an ORR of 42.9% and PFS of 6.5 months.
  • Common toxicities include diarrhea, musculoskeletal pain, fatigue, and hepatotoxicity.

Conclusions:

  • Sotorasib and adagrasib offer new therapeutic options for KRAS G12C-mutated NSCLC.
  • Current guidelines recommend them as second-line treatments.
  • Further studies are needed to differentiate their profiles and establish optimal use.
Keywords:
KRAS inhibitoradagrasibkrazatilumakrasnon–small cell lung cancersmall molecule inhibitorsotorasib

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