First-Line Osimertinib Plus Chemo Boosts OS in EGFR+ NSCLC

EGFR+ NSCLC | Image by Ashling Wahner

& MJH Life Sciences Using AI

First-line treatment with the combination of osimertinib (Tagrisso) in combination with chemotherapy led to a statistically significant and clinically meaningful improvement in overall survival (OS) compared with osimertinib alone in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations, according to data from the final analysis of the phase 3 FLAURA2 trial (NCT04035486).1

The data in the final OS analysis were consistent with previously reported findings. Detailed findings will be reported at an upcoming medical meeting.

“When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in first line where treatment duration can be long and many patients remain active,” Pasi A. Jänne, MD, PhD, senior vice president for Translational Medicine and thoracic medical oncologist at Dana-Farber Cancer Institute, and principal investigator for the FLAURA2 trial, stated in a news release. “These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with first-line advanced EGFR-mutated lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression.”

In February 2024, the FDA approved osimertinib in combination with platinum-based chemotherapy for use in patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.2 This was based on prior data from FLAURA2.

Findings supporting the approval showed that patients treated with osimertinib plus chemotherapy experienced a median progression-free survival (PFS) of 25.5 months (95% CI, 24.7-not evaluable) compared with 16.7 months (95% CI, 14.1-21.3) for those given osimertinib alone (HR, 0.62; 95% CI, 0.49-0.79; 2-sided P <.0001).

Regarding safety, the most common adverse effects reported in at least 20% of patients treated with osimertinib plus chemotherapy comprised leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine levels.

FLAURA2 Deep Dive

The randomized, multicenter, open-label, phase 3 FLAURA2 trial enrolled patients at least 18 years of age with locally advanced or metastatic NCSLC harboring an EGFR exon 19 deletion or exon 21 L858R mutations who did not receive prior systemic therapy in the advanced setting.3 Patients were required to have measurable disease by RECIST 1.1 criteria and a World Health Organization (WHO) performance status of 0 or 1.

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

Along with the primary end point of PFS, OS served as a key secondary end point. Other secondary end points comprised duration of response, objective response rate, disease control rate, time to second progression, quality of life, and safety.

References

1. Tagrisso (osimertinib) plus chemotherapy demonstrated statistically significant and clinically meaningful improvement in overall survival in EGFR-mutated advanced lung cancer. News release. AstraZeneca. July 21, 2025. Accessed July 21, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/tagrisso-plus-chemotherapy-demonstrated-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-in-egfr-mutated-advanced-lung-cancer.html
2. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung cancer. FDA. February 16, 2024. Accessed July 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer
3. A study of osimertinib with or without chemotherapy as 1st line treatment in patients with mutated epidermal growth factor receptor non-small cell lung cancer (FLAURA2). ClinicalTrials.gov. Updated July 4, 2025. Accessed July 21, 2025. https://www.clinicaltrials.gov/study/NCT04035486