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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Friday, February 9, 2024
The EGFR tyrosine kinase inhibitor osimertinib plus chemotherapy prolonged progression-free survival significantly further than osimertinib alone (P < .001) in patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced non–small cell lung cancer (NSCLC) who had not previously received treatment for advanced disease, according to the results of the phase III FLAURA2 trial, which involved more than 500 patients. These findings from David Planchard, MD, PhD, of Institut Gustave Roussy, Villejuif, France, and colleagues were published in The New England Journal of Medicine.
At 24 months, 57% and 41% of the patients given osimertinib plus chemotherapy and osimertinib alone were progression-free. Chemotherapy consisted of pemetrexed plus either cisplatin or carboplatin. Additionally, “an objective (complete or partial) response was observed in 83% of the patients in the osimertinib/chemotherapy group and in 76% of those in the osimertinib group,” wrote the team. “The median response duration was 24.0 months and 15.3 months, respectively.” The combination was associated with a higher incidence of grade 3 or higher adverse events from any cause than osimertinib monotherapy; the investigators believe the chemotherapy is at the heart of this finding.
Why the combination gave rise to the observed clinical benefit isn’t yet known, the authors noted. “It is possible the combination therapy may overcome intratumor heterogeneity by eliciting an additive effect by means of the killing of different cell populations to improve clinical outcomes,” they proposed. Dr. Planchard and co-investigators suggested that ongoing exploratory analyses, including circulating tumor DNA–based analyses, may provide insights into predictive biomarkers for the combination therapy.
Disclosure: For full disclosures of the study authors, visit nejm.org.
The New England Journal of Medicine
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