(ChemotherapyAdvisor) – Despite high response rates and improved progression-free survival (PFS) observed with gefitinib in patients with lung adenocarcinoma who have never smoked, a recent study in a chemotherapy-naïve Korean population failed to demonstrate superior overall survival (OS) for gefitinib vs. gemcitabine plus cisplatin, results of the randomized, Phase 3 First-SIGNAL trial in the Journal of Clinical Oncology published online February 27 found.

The study investigators analyzed per-protocol data on patients with stage IIIB or IV lung adenocarcinoma who received either gefitinib 250mg/day (n=159) or gemcitabine 1,250mg/m2 on days 1 and 8 plus cisplatin 80mg/m2 on day 1 (n=150) every three weeks for up to nine courses.

Compared with gemcitabine plus cisplatin, gefitinib did not show better OS (HR=0.932; P=0.604), the primary end point. Median OS was 22.9 months for gefitinib and 22.3 months for gemcitabine plus cisplatin. At one year, rates of progression-free survival (PFS) were 16.7% with gefitinib and 2.8% with gemcitabine plus cisplatin (HR=1.198); response rates were 55% and 46%, respectively (P=0.101).

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In the gefitinib arm, skin toxicities and liver dysfunction were more common than in the gemcitabine plus cisplatin arm, where myelosuppression, renal insufficiency, and fatigue were more common. Two deaths occurred from interstitial lung disease in the gefitinib arm.

The investigators surmised that lack of an OS benefit was availability, after the study was initiated, of EGFR-TKIs in Korea; 75% of patients in the gemcitabine plus cisplatin arm received an EGFR-TKI after discontinuation of the assigned treatment. In addition, patients in this study received up to 9 cycles of the combination therapy, contrasting with 4 to 6 cycles in previous studies. “As demonstrated in previous randomized Phase 3 trials, the relatively longer duration of effective treatment here may in part have contributed to the prolongation of PFS in the gemcitabine plus cisplatin arm,” they wrote.

The “unprecedented” median OS supports the idea that gefitinib can provide a benefit in this patient population. “To optimize selecting patients for first-line gefitinib, EGFR mutation testing is needed,” the study authors concluded.