The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On February 16, 2024, the Food and Drug Administration approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals LP) 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 mutations, as detected by an FDA-approved test.
Full prescribing information for Tagrisso will be posted here.
Efficacy was evaluated in FLAURA 2 (NCT04035486), an open-label, randomized trial of 557 patients with EGFR exon 19 deletion or exon 21 L858R mutation-positive la/mNSCLC and no 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 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% Confidence Interval [CI]: 0.49, 0.79; two-sided p-value<0.0001). The median PFS was 25.5 months (95% CI: 24.7, not estimable [NE]) and 16.7 months (95% CI: 14.1, 21.3) in the respective arms.
While OS results were immature at the current analysis, with 45% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.
The most common adverse reactions (≥ 20% incidence) in 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 disease progression or unacceptable toxicity. Refer to the prescribing information for pemetrexed and cisplatin or carboplatin for the respective dosing information.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and breakthrough 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 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology.
