medwireNews: People with EGFR-mutated advanced non-small-cell lung cancer (NSCLC) derive a significant progression-free survival (PFS) benefit when first-line osimertinib is supplemented with chemotherapy, finds the FLAURA2 trial.
The median PFS was almost 9 months longer with osimertinib plus chemotherapy than osimertinib alone, report the researchers in The New England Journal of Medicine, a result that the authors of an accompanying editorial describe as “truly remarkable” and “a great step” forward.
Yi‑Long Wu and Qing Zhou, both from Southern Medical University in Guangzhou, China, say that in light of these findings, the combination “would absolutely become an option” for this patient population, but “some questions still need to be addressed.” These include whether the benefits outweigh the risks of combined treatment and whether the FLAURA2 regimen prolongs overall survival (OS).
For the phase 3 study, David Planchard (Institut Gustave Roussy, Villejuif, France) and collaborators recruited 557 individuals with locally advanced or metastatic NSCLC positive for an EGFR exon 19 deletion or L858R mutation who had not received prior systemic therapy for advanced disease.
The patients were randomly assigned to receive osimertinib 80 mg/day either with or without cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL per min plus pemetrexed 500 mg/m2 every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed, with both drugs continued at the same doses.
At a median follow-up of 16.5–19.5 months, the primary endpoint of investigator-assessed PFS was a median of 25.5 months in the osimertinib plus chemotherapy arm and 16.7 months in the osimertinib monotherapy arm, a significant difference equating to a hazard ratio (HR) for progression or death of 0.62 in favor of the combination.
The PFS rate at 24 months was 57% and 41%, respectively, report the investigators, adding that the findings were consistent when PFS was assessed by blinded independent central review.
They continue: “The progression-free survival benefit with osimertinib plus chemotherapy appeared to be consistent across prespecified subgroups, including the subgroups defined according to EGFR mutation type and the presence or absence of [central nervous system] metastases at baseline.”
The combined regimen was also associated with a higher objective response rate and median duration of response than osimertinib alone, at 83% versus 76%, and 24.0 versus 15.3 months, respectively.
Planchard and colleagues note that the OS data were not mature at the time of analysis, “but indicated that the addition of chemotherapy to osimertinib was not detrimental to survival.” They add that “further follow-up is required.”
The improved outcomes with the combination came at the cost of increased toxicity, but the study authors emphasize that this was “driven by known chemotherapy-related adverse events [AEs].”
AEs of at least grade 3 occurred in 64% of patients given osimertinib plus chemotherapy and 27% of those treated with osimertinib alone. Serious AEs were observed in a respective 38% and 19%, and osimertinib was discontinued by 11% and 6%. Five deaths in the combination arm were considered possibly related to study treatment versus one in the osimertinib alone arm.
“Taken together, the results of this trial support the combination of osimertinib plus platinum–pemetrexed as a new treatment option for patients,” conclude the FLAURA2 investigators.
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