The FDA granted accelerated approval to oral sotorasib (Lumakras) as a second-line treatment for adult patients with non-small cell lung cancer (NSCLC) with KRAS G12C mutations.
KRAS mutations account for roughly 25% of mutations in NSCLCs, and KRAS G12C in particular accounts for 13% of NSCLC mutations. This FDA decision made sotorasib the first approved targeted therapy for tumors with any KRAS mutations—however, the agency noted that further study is needed to verify and describe the drug’s clinical benefit.
“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach.”
This approval was based on results from a study that evaluated the efficacy of sotorasib in a cohort of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC whose disease progressed following treatment with an immune checkpoint inhibitor and/or platinum-based chemotherapy. “The objective response rate was 36%, and 58% of those patients had a duration of response of six months or longer,” the FDA explained.
Based on the available clinical data, sotorasib has been approved in a 960-milligram dose; the FDA is requiring the manufacturer to conduct a post-marketing trial to investigate whether a lower dose will have a similar clinical effect as part of the accelerated approval.
The most common side effects of sotorasib included diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Patients taking the drug should also be monitored for interstitial lung disease/pneumonitis and hepatoxicity, and treatment should be withheld if patients experience either condition during treatment. “Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of the P-glycoprotein while taking [sotorasib],” the FDA added.
Sotorasib is manufactured by Amgen Inc.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 24
Topic ID: 78,24,730,24,192,725,65,925
