First-line osimertinib combined with chemotherapy can enhance OS of EGFR+ non-small cell lung cancer

According to the final analysis of data from the phase 3 FLAURA2 trial (NCT04035486), patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and In patients with EGFR mutations, first-line treatment with osimertinib combined with chemotherapy achieved statistically significant and clinically meaningful improvements in overall survival (OS) compared with osimertinib/Tagressa alone. The data in the final OS analysis were consistent with previously reported results.

When treating lung cancer, our goal is to extend survival and improve patient experience, especially in the front line, where treatment duration can be long and many patients remain active. These positive results support osimertinib as monotherapy or in combination with chemotherapy as a standard treatment for patients with first-line advanced EGFR-mutated lung cancer and reinforce the meaningful benefit of combination therapy in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 does not impose any restrictions on subsequent treatment options after disease progression.

In February 2024, the FDA approved osimertinib in combination with platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer who carry EGFR exon 19 deletions or exon 21 L858R mutations as detected by an FDA-approved test. This is based on previous data from FLAURA2.

Results from studies supporting the approval showed that median progression-free survival (PFS) was 25.5 months (95% CI, 24.7-not evaluable) in patients who received osimertinib plus chemotherapy compared with 16.7 months (95% CI, 14.1-21.3) in patients who received osimertinib alone (HR, 0.62; 95% CI, 0.49-0.79; two-sided P <.0001).

Regarding safety, the most common adverse reactions reported by at least20% of patients who received osimertinib in combination with chemotherapy included leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased serum creatinine levels.

FLAURA2 trial

This randomized, multicenter, open-label studyThe phase 3 FLAURA2 trial enrolled patients at least 18 years of age with locally advanced or metastatic non-small cell lung cancer who harbored an EGFR exon 19 deletion or exon 21 L858R mutation and who had not received systemic therapy in the advanced setting. 3 Patients need to have measurable disease as defined by RECIST 1.1 criteria and a World Health Organization performance status of 0 or 1.

Eligible patients were randomly assigned1:1 to receive 80 mg/day of osimertinib twice daily, plus 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin, or carboplatin with an area under the curve of 5 on day 1 of each 21-day cycle for 4 cycles, followed by 80 mg/day of osimertinib plus 500 mg/m2 of cisplatin every 3 weeks. mg/m2 of pemetrexed; or 80 mg of osimertinib once daily. Treatment was continued until intolerable toxicity or lack of clinical benefit.

Like the primary endpoint of PFS, OS is also an important secondary endpoint. Other secondary endpoints include duration of response, objective response rate, disease control rate, time to second progression, quality of life and safety.

Reference materials:https://go.drugbank.com/drugs/DB09330