European Commission Approves Osimertinib Plus Chemo for Advanced EGFR+ NSCLC

David Planchard, MD, PhD

Frontline osimertinib (Tagrisso) in combination with pemetrexed and platinum-based chemotherapy has been approved in the European Union for adult patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations.¹

This regulatory decision was based on findings from the phase 3 FLAURA2 trial (NCT04035486), which also supported the positive opinion on the use of this combination in this indication by the European Medicines Agency’s Committee for Medicinal Products for Human Use. Findings from FLAURA2, which were published in The New England Journal of Medicine, showed that osimertinib plus chemotherapy elicited a median investigator-assessed progression-free survival (PFS) of 25.5 months (95% CI, 24.7–not calculable [NC]) vs 16.7 months (95% CI, 14.1-21.3) with osimertinib monotherapy (HR, 0.62; 95% CI, 0.49-0.79; P < .0001).^1,2 The median PFS by blinded independent central review (BICR) was 29.4 months (95% CI, 25.1-NC) with osimertinib plus chemotherapy vs 19.9 months (95% CI, 16.6-25.3) with osimertinib alone (HR, 0.62; 95% CI, 0.48-0.80; nominal P = .0002).

Furthermore, a prespecified exploratory analysis of patients in FLAURA2 with brain metastases at baseline demonstrated that osimertinib plus chemotherapy resulted in a 42% reduction in the risk of BICR-assessed central nervous system (CNS) disease progression or death vs osimertinib monotherapy (HR, 0.58; 95% CI, 0.33-1.01).¹ At a median follow-up of 2 years, 74% of patients who received osimertinib plus chemotherapy had not experienced CNS disease progression or death compared with 54% of those who received osimertinib alone.

Although the overall survival (OS) data were immature at the second interim analysis, investigators observed a trend favoring osimertinib plus chemotherapy vs osimertinib monotherapy (HR, 0.75; 95% CI, 0.57-0.97). The 24-month OS rates in the combination and monotherapy arms were 79% (95% CI, 73%-83%) and 73% (95% CI, 67%-78%), respectively. FLAURA2 will continue to evaluate OS as a key secondary end point.

“[This approval] marks a significant advance for patients with EGFR-mutated lung cancer in Europe, providing a new first-line treatment option with osimertinib now in combination with chemotherapy,” David Planchard, MD, PhD, a thoracic oncologist at Gustave Roussy Institute of Oncology in Villejuif, France, and principal investigator of FLAURA2, stated in a news release. “The FLAURA2 results build on the established efficacy of osimertinib monotherapy, showing a meaningful [8.8]-month improvement in PFS and offering physicians the option to tailor treatment to a patient’s specific needs.”

“This approval reinforces [osimertinib] as the backbone therapy in EGFR-mutated lung cancer either as monotherapy or in combination with chemotherapy,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, added in the press release. “This is especially important for [patients] with more aggressive disease, including patients whose cancer has spread to the brain and those with L858R mutations.”

The press release noted that the safety profile of osimertinib in combination with chemotherapy observed during FLAURA2 was consistent with the established safety profiles of the individual agents. Higher rates of adverse effects (AEs) were observed in the combination arm compared with the monotherapy arm due to well-characterized chemotherapy-related AEs. Eleven percent of patients in the combination arm discontinued osimertinib because of AEs vs 6% of those in the monotherapy arm.

Osimertinib in combination with chemotherapy was approved by the FDA in 2024 for the frontline treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations.³

References

1. Tagrisso with the addition of chemotherapy approved in the EU as new 1st-line treatment for patients with EGFR-mutated advanced lung cancer. News release. AstraZeneca. July 5, 2024. Accessed July 8, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-with-the-addition-of-chemotherapy-approved-in-the-eu-as-new-1st-line-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer.html
2. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
3. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung cancer. FDA. February 16, 2024. Accessed February 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer