On February 16, 2024, the U.S. Food and Drug Administration (FDA) approved osimertinib (Tagrisso®) with platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (la/mNSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R variants, as detected by an FDA-approved test.

FDA update

Efficacy was evaluated in FLAURA 2 (NCT04035486), an open-label, randomized trial of 557 patients with EGFR exon 19 deletion– or exon 21 L858R variant–positive la/mNSCLC who had not received prior systemic therapy for advanced disease. Patients were randomized 1:1 to receive either osimertinib with platinum-based chemotherapy or osimertinib monotherapy.

The major efficacy outcome measure was progression free survival (PFS), as assessed by the investigator, with overall survival (OS) as a key secondary outcome measure. Osimertinib plus platinum-based chemotherapy demonstrated a statistically significant improvement in PFS compared to osimertinib monotherapy with a hazard ratio of 0.62 (95% CI = 0.49, 0.79; two-sided p < 0.0001). The median PFS was 25.5 months (95% CI = 24.7, not estimable) and 16.7 months (95% CI = 14.1, 21.3) in the respective arms.

Although OS results were immature at the time of the analysis, with 45% of prespecified deaths reported for the final analysis, researchers did not observe any trend toward a detriment.

The most common adverse reactions reported in at least 20% of patients receiving osimertinib plus platinum-based chemotherapy were leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine.

The recommended osimertinib dose is 80 mg orally once daily, with or without food, until patients experience disease progression or unacceptable toxicity. View the prescribing information for osimertinib. Refer to the prescribing information for pemetrexed and cisplatin or carboplatin for those agents’ dosing information.

The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For its review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. FDA also used Assessment Aid, a voluntary submission from the applicant, to facilitate its assessment.

FDA granted the application priority review and fast-track, regenerative medicine advanced therapy, and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.