FDA Expands Approval of Osimertinib in Lung Cancer

The FDA has approved osimertinib (Tagrisso) for locally advanced, unresectable stage III non-small cell lung cancer (NSCLC) following chemoradiotherapy, the agency announced Wednesday.

The EGFR inhibitor is specifically indicated for adults whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiotherapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations as detected by an FDA-approved test.

Approval was based on data from the LAURA trial, the results of which were presented at the American Society of Clinical Oncology (ASCO) annual meeting in June.

In the phase III trial, median progression-free survival (PFS) increased seven-fold when patients received osimertinib after definitive chemoradiation, improving from 5.6 months with placebo to 39.1 months with osimertinib (HR 0.16, 95% CI 0.10-0.24, P<0.001).

During an ASCO press conference, investigator Suresh Ramalingam, MD, of the Winship Cancer Institute at Emory University School of Medicine in Atlanta, said that LAURA’s results suggested that osimertinib “will become the new standard of care for patients with locally advanced non-small cell lung cancer following definitive chemoradiation.”

While overall survival results were immature, with 36% of prespecified deaths for the final analysis reported, no trend toward a survival disadvantage was observed, the FDA said.

As reported at ASCO, the PFS rates were 74% and 65% at 1 and 2 years in the osimertinib arm versus 22% and 13% in the placebo arm, while objective response rates were 57% and 33%, respectively, with a median duration of response of 36.9 months versus 6.5 months.

“This will be practice changing,” said David Spigel, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee, during the ASCO press conference. “It really is outstanding.”

LAURA was a double-blind, randomized, placebo-controlled trial that included 216 adult patients with unresectable stage III NSCLC who had undergone definitive chemoradiation, had no evidence of disease progression during or after it, and harbored EGFR mutations. Patients were randomized 2:1 to receive oral osimertinib (80 mg per day) or placebo until disease progression or unacceptable toxicity.

The most common adverse reactions (≥20%) with osimertinib, including laboratory abnormalities, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.

Osimertinib was first approved in 2015. The tyrosine kinase inhibitor is also approved as first-line therapy for metastatic EGFR-mutant NSCLC (alone or with chemotherapy) and as adjuvant therapy for operable EGFR-mutant NSCLC, among other indications.

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