FDA Grants Accelerated Approval of Sotorasib for Patients with NSCLC-Harboring KRAS Mutations

Web Exclusives —June 23, 2021

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Lung Cancer

Lung cancer is one of the most common cancer types worldwide and has a high mortality rate.1 Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 84% of all cases.1 NSCLC can be categorized based on the genetic mutations that cause it. The KRAS mutation occurs in approximately 25% of all cases, while KRASG12C mutations represent approximately 13% of these mutations.1 The KRAS mutations have long been considered to be resistant to drug therapy and are often associated with poor patient prognosis.1

On May 28, 2021, the US Food and Drug Administration (FDA) granted accelerated approval for sotorasib as a treatment for adult patients with NSCLC-harboring KRASG12C mutations who have received ≥1 prior treatments. This is the first approved targeted therapy for any KRAS mutation. Approval was granted based on data from a subset of 124 patients from the CodeBreaK 100 clinical trial with locally advanced or metastatic KRASG12C-mutated NSCLC with disease progression after receiving either an immune checkpoint inhibitor, platinum-based chemotherapy, or both therapies.2

The study’s major outcomes were objective response rate and duration of response. More than a third of the patients (36%) had a confirmed response to sotorasib, with 58% of patients having a duration of response of ≥6 months. Disease control (complete response, partial response, and stable disease for >3 months) was experienced by 81% of patients.2 The approved dose is 960 mg, although the FDA is requiring a postmarketing trial to investigate, as part of the accelerated approval pathway, whether a lower dose will have clinical benefit.2

The most common adverse events experienced with sotorasib use include diarrhea, cough, fatigue, musculoskeletal pain, nausea, and liver damage.2 Permanent discontinuation due to adverse reactions occurred in 9% of patients in the study. Interstitial lung disease (ILD) is a concern with sotorasib, and use should be withheld if symptoms of ILD develop and permanently discontinued if ILD is diagnosed.2 Liver function should be monitored before and during treatment.2 If liver damage is detected, dosage reduction is advised or treatment should be stopped.2 In addition, acid-reducing agents, drugs that induce or are substrates for certain liver enzymes, and drugs that are P-glycoprotein substrates should be avoided during sotorasib treatment.2

Along with this approval, the FDA also approved the QIAGEN therascreen KRAS RGQ PCR kit, which analyzes tumor tissue, and the Guardant360 CDx, which analyzes plasma specimens. Both tests will determine if sotorasib is an appropriate treatment for NSCLC patients.2


References

  1. American Cancer Society. Key Statistics for Lung Cancer 2021. www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed June 1, 2021.
  2. US Food and Drug Administration. FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy. www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-lung-cancer-mutation-previously-considered-resistant-drug. Accessed June 1, 2021.
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Last modified: August 10, 2023

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