Dr Iams on the Impact of Adagrasib on Patient Outcomes in KRAS G12C–Mutant NSCLC

Wade T. Iams, MD, assistant professor of medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, discusses the impact of adagrasib (Krazati) on the treatment of patients with KRAS G12C-mutant non–small cell lung cancer (NSCLC) in the second line, as well as its integration into clinical practice.

The introduction of KRAS G12C inhibitors to this treatment armamentarium has significantly improved outcomes for patients with KRAS G12C-mutant NSCLC. Adagrasib has emerged as a key therapeutic option for this patient population following its accelerated approval by the FDA for adult patients with KRAS G12C–mutated locally advanced or metastatic NSCLC who received at least 1 prior systemic therapy, Iams states.

This regulatory decision, which was made on December 12, 2022, was based on data from the phase 1/2 KRYSTAL-1 trial (NCT03785249), showing that the agent produced an objective response rate of 43% in this population and a median duration of response of 8.5 months.

Prior to the approval of KRAS G12C inhibitors, patients with this mutation had limited second– or later-line treatment choices, Iams says. Commonly utilized approaches included chemotherapy regimens such as docetaxel with or without ramucirumab (Cyramza) or gemcitabine; however, these options are often associated with challenging toxicities and less favorable outcomes, he explains.

Adagrasib has been well-received in the clinical setting, Iams reports. It exhibits a manageable toxicity profile, and healthcare providers can employ a dose-reduction strategy to effectively address any adverse events that may arise during treatment, he adds. This enhances the drug's tolerability and allows more patients to benefit from its therapeutic effects, Iams says.

As a result, the approval and utilization of adagrasib and other KRAS G12C inhibitors have expanded the available treatment choices for patients with KRAS G12C-mutant NSCLC, Iams states. These inhibitors have demonstrated their potential to be more effective than traditional chemotherapy options, ultimately enhancing the quality of life for patients and improving outcomes, Iams concludes.