FDA Approves Osimertinib for Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer Following Chemoradiation Therapy
On September 25, 2024, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-locally-advanced-unresectable-stage-iii-non-small-cell-lung-cancer) osimertinib (Tagrisso®) for 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 variants, as detected by an FDA-approved test.
Efficacy was evaluated in LAURA (NCT03521154), a double-blind, randomized, placebo-controlled trial in 216 adult patients with locally advanced, unresectable, stage III NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who had not progressed during or following definitive platinum-based chemoradiation within 42 days prior to study randomization. Patients were randomized 2:1 to receive either osimertinib 80 mg orally once daily or placebo until they experienced disease progression or unacceptable toxicity.
The major efficacy outcome measure was progression free survival (PFS) as assessed by blinded independent central review. Additional efficacy outcome measures included overall survival (OS). Osimertinib demonstrated a statistically significant improvement in PFS compared to placebo with a hazard ratio of 0.16 (95% CI = 0.10, 0.24; p < 0.001). The median PFS was 39.1 months (95% CI = 31.5, not estimable) in the osimertinib arm and 5.6 months (95% CI = 3.7, 7.4) in the placebo arm. Although OS results were immature for the current analysis, with 36% of prespecified deaths for the final analysis reported, the researchers did not observe any trend toward a detriment.
The most common adverse reactions, including laboratory abnormalities, reported in at least 20% of patients were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
The recommended osimertinib dose is 80 mg once daily, with or without food, until patients experience disease progression or unacceptable toxicity. View the full prescribing information for osimertinib on Drugs@FDA (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm).
The FDA conducted its review under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an Oncology Center of Excellence (OCE) initiative. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
The applicant used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid) to facilitate the FDA’s review. The FDA granted the application priority review and breakthrough designation. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).