FDA Approves Osimertinib for Locally Advanced, Unresectable EGFR+ NSCLC After Chemoradiation

FDA

The FDA approved osimertinib (Tagrisso) for the treatment of adult patients with locally advanced, unresectable, stage III non–small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.¹

The regulatory decision was supported by data from the phase 3 LAURA trial (NCT03521154), which showed that patients treated with osimertinib (n = 143) experienced a median progression-free survival (PFS) of 39.1 months (95% CI, 31.5–not estimable [NE]) compared with 5.6 months (95% CI, 3.7-7.4) for those given placebo (n = 73; HR, 0.16; 95% CI, 0.10-0.24; P < .001). Data presented at the 2024 ASCO Annual Meeting showed that the 12- and 24-month PFS rates in the osimertinib arm were 74% and 65%, respectively; those respective rates were 22% and 13% in the placebo arm.²

LAURA was a randomized, double-blind study that enrolled patients at least 18 years of age (or at least 20 years of age in Japan) with locally advanced, unresectable stage III NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations who did not experience disease progression during or after definitive chemoradiation. Key inclusion criteria consisted of a WHO performance status of 0 or 1, and a maximum interval between the last dose of chemoradiation and randomization of 6 weeks.

Patients were randomly assigned 2:1 to receive osimertinib at 80 mg or placebo once per day until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Patients in both arms were allowed to cross over to receive open-label osimertinib following confirmed disease progression.

Stratification factors included chemoradiation type (concurrent vs sequential), stage (IIIA vs IIIB/C), and region (China vs other).

Blinded independent central review (BICR)–assessed PFS per RECIST 1.1 criteria served as the trial's primary end point. Secondary end points included overall survival (OS), central nervous system PFS, and safety.

At 20% maturity, the median OS was 54.0 months (95% CI, 46.5–not calculable [NC]) in the osimertinib arm vs not reached (95% CI, 42.1-NC) in the placebo arm (HR, 0.81; 95% CI, 0.42-1.56; P =.530). Notably, 81% of patients in the placebo arm with BICR-confirmed disease progression crossed over to receive osimertinib.

Osimertinib elicited an objective response rate of 57% (95% CI, 49%-66%) compared with 33% (95% CI, 22%-45%) for placebo. The disease control rate was 89% (95% CI, 83%-94%) and 79% (95% CI, 68%-88%), respectively. The median duration of response was 36.9 months (95% CI, 30.1-NC) for osimertinib and 6.5 months (95% CI, 3.6-8.3) for placebo.

Twenty-two patients in the osimertinib arm experienced new lesions compared with 68 patients in the placebo arm. Sites of new lesions included the brain (osimertinib, n = 8; placebo, n = 29), lung (n = 6; n = 29), liver (n = 3; n = 7), lymph nodes (n = 1; n = 7), bone (n = 1; n = 1), adrenal (n = 1; n = 0), peritoneum/omentum (n = 1; n = 0), pelvis (n = 1; n = 0), spleen (n = 0; n = 1), and other (n = 1; n = 0).

The most common adverse effects reported in at least 20% of patients included lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.¹

References

1. FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy. FDA. September 25, 2024. Accessed September 25, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-locally-advanced-unresectable-stage-iii-non-small-cell-lung-cancer
2. Ramalingam SS, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. J Clin Oncol. 2024;42(suppl 17):LBA4. doi:10.1200/JCO.2024.42.17_suppl.LBA4