Dr Jänne on the FDA Approval of Osimertinib Plus Chemotherapy in EGFR+ mNSCLC

Pasi A. Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology, director, Belfer Center for Applied Cancer Science, director, Chen-Huang Center for EGFR Mutant Lung Cancers, senior physician, David M. Livingston, MD, Chair, Dana-Farber Cancer Institute; professor, medicine, Harvard Medical School, discusses the significance of the FDA approval of osimertinib (Tagrisso) in combination with chemotherapy in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations.

On February 16, 2024, the FDA approved osimertinib plus chemotherapy for patients with EGFR-mutated metastatic or locally advanced NSCLC. This regulatory decision was supported by findings from the phase 3 FLAURA2 trial (NCT04035486).

Osimertinib plus chemotherapy is the first FDA-approved, osimertinib-containing combination regimen for patients with EGFR-mutant lung cancer, Jänne says. Data from FLAURA2 demonstrated that the addition of chemotherapy to first-line osimertinib generated an 8.8-month improvement in investigator-assessed median progression-free survival (PFS) vs osimertinib alone. The PFS findings by blinded independent central review were consistent with the improvement in investigator-assessed median PFS, showing that the combination improved median PFS by 9.5 months vs osimertinib alone (HR, 0.62; 95% CI, 0.48-0.80; P = .0002). The PFS benefit seen with the combination was significant and clinically meaningful, Jänne notes. Although the combination regimen was associated with added toxicities vs osimertinib monotherapy, osimertinib plus chemotherapy was well tolerated in most patients, Jänne emphasizes.

Furthermore, the combination improved the median intracranial PFS in patients with baseline central nervous system (CNS) metastases, according to Jänne. In this population, osimertinib plus chemotherapy reduced the risk of disease progression or death by 53% vs osimertinib monotherapy (HR, 0.47; 95% CI, 0.33-0.66). Additionally, more patients with CNS metastases who received the combination achieved complete clearance of their CNS metastases than those who received osimertinib alone, Jänne explains. Overall, osimertinib plus chemotherapy delivers several benefits compared with single-agent osimertinib, and is an exciting treatment option for patients with EGFR-mutated locally advanced or metastatic NSCLC, Jänne concludes.