First Targeted Therapy for Certain Patients With NSCLC Granted FDA Approval


Lung cancer, the most common cancer type with the highest mortality, can largely be categorized by the genetic mutations that cause it.

Officials with the FDA have approved sotorasib (Lumakras; Amgen) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) whose tumors have the KRAS G12C genetic mutation and who have received at least 1 prior systemic therapy. According to the FDA, the approval is the first for a targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in NSCLCs. KRAS G12C represents approximately 13% of mutations in NSCLCs.

Lung cancer, the most common cancer type with the highest mortality, can largely be categorized by the genetic mutations that cause it. KRAS is a type of mutation in a group of genes that help regulate cell growth and division.

"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, MD, 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, in a press release. "Today's approval represents a significant step towards a future where more patients will have a personalized treatment approach."

Researchers evaluated the efficacy of sotorasib in a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy. The major outcomes measured were objective response rate (ORR)—proportion of patients whose tumor is destroyed or reduced—and duration of response (DOR). The ORR rate was 36%, and 58% of those patients had a DOR of 6 months or longer.

The approved 960 milligram dose is based on available clinical data, as well as pharmacokinetic and pharmacodynamic modeling that support the approved dose. As part of the evaluation for the FDA’s accelerated approval of sotorasib, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common adverse effects of sotorasib include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. According to the FDA, sotorasib should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed.

Additionally, health care professionals should monitor a patient's liver function tests prior to starting and when taking sotorasib. The drug should be withheld, dose reduced, or permanently discontinued if a patient develops liver damage. 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 also granted Fast Track, Priority Review, Breakthrough Therapy, and Orphan Drug designations to Amgen’s application for sotorasib approval.


FDA Approves First Targeted Therapy for Lung Cancer Mutation Previously Considered Resistant to Drug Therapy [news release]. May 28, 2021; FDA. Accessed June 1, 2021.

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