Osimertinib and Amivantamab Gain FDA Approval for EGFR-Mutated NSCLC
Key Insights
Osimertinib receives FDA approval for unresectable Stage III EGFR (search)-mutated NSCLC (search) after chemoradiation, showing a significant increase in progression-free survival.
Amivantamab, combined with chemotherapy, gains FDA approval for EGFR (search) exon 19 deletions or exon 21 L858R substitution mutations in NSCLC (search) after EGFR TKI treatment.
Clinical trials, including LAURA (search) and MARIPOSA-2 (search), support these approvals, offering new targeted therapy options for patients with advanced NSCLC (search).
The FDA has recently approved two targeted therapies, osimertinib and amivantamab, for specific subsets of non-small cell lung cancer (NSCLC (search)) with epidermal growth factor receptor (EGFR (search)) mutations, marking significant advancements in the treatment landscape for this disease. These approvals cater to different stages and treatment histories of EGFR-mutated NSCLC, providing new options for patients who have previously had limited choices.
Osimertinib Approved for Stage III NSCLC
The FDA approved osimertinib (Tagrisso) for adult patients with locally advanced, unresectable Stage III NSCLC (search) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy. Patients must also have tumors with EGFR (search) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
This approval was based on data from the phase 3 LAURA (search) trial, a randomized, double-blind, placebo-controlled study involving 216 patients. The trial demonstrated that osimertinib significantly improved progression-free survival (PFS) compared to placebo. According to the study results, treatment with osimertinib reduced the risk of disease progression or death by 84% compared to placebo (HR, 0.16; 95% CI, 0.10-0.24; P < .001). The median PFS was 39.1 months in the osimertinib arm and 5.6 months in the placebo arm.
Suresh Ramalingam, MD, Executive Director of Winship Cancer Institute of Emory University and principal investigator in the trial, noted, "This approval represents a major breakthrough for patients with Stage III, EGFR (search)-mutated lung cancer who will now have the opportunity to benefit from osimertinib."
Amivantamab Approved for NSCLC After EGFR TKI Treatment
The FDA also approved amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed for adult patients with locally advanced or metastatic NSCLC (search) harboring EGFR (search) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).
The approval was based on data from the phase 3 MARIPOSA-2 (search) trial, a randomized, open-label study that evaluated the efficacy and safety of amivantamab plus chemotherapy. The study showed that the median progression-free survival (PFS) was 6.3 months (95% CI, 5.6-8.4) in the amivantamab arm compared with 4.2 months (95% CI, 4.0-4.4) in the chemotherapy arm (HR, 0.48; 95% CI, 0.36-0.64; P < .0001). Amivantamab plus chemotherapy elicited a confirmed overall response rate of 53% (95% CI, 44%-62%) vs 29% (95% CI, 23%-35%) for chemotherapy alone.
Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard, stated that the combination may address the most common mechanisms of treatment resistance to third-generation EGFR (search) TKIs, offering an effective new second-line option for patients.
Clinical Implications
These approvals offer new hope for patients with EGFR (search)-mutated NSCLC (search). Osimertinib provides a targeted treatment option for patients with Stage III disease following chemoradiation, while amivantamab offers a new approach for patients whose disease progresses after initial EGFR TKI therapy. Both approvals underscore the importance of EGFR mutation testing in NSCLC to guide treatment decisions.