Afatinib tops gefitinib in head-to-head trial
LUX-Lung 7, a global phase IIb, randomized, open-label trial, demonstrated significant improvements in progression-free survival (PFS), time to treatment failure (TTF) and objective response rate (ORR) with afatinib vs gefitinib as first-line treatment for patients with advanced, EGFR-positive non-small-cell lung cancer (NSCLC). [ELCC 2016, abstract 140PD]
Patients were randomized to receive afatinib (n=160) or gefitinib (n=159) until radiological disease progression or beyond, by investigator decision. Baseline characteristics in terms of ethnicity and type of EGFR mutation were well balanced between the two arms. The co-primary endpoints were PFS by independent review, TTF and overall survival (OS).
“PFS was prolonged by 27 percent with afatinib vs gefitinib, as was TTF [hazard ratio, 0.73; p=0.007]. Consistent treatment benefit was observed across subgroups including race and mutation type,” said lead investigator Dr. Keunchil Park of the Samsung Medical Centre in Seoul, South Korea. “Independently assessed ORR, a secondary endpoint of the study, was significantly higher with afatinib vs gefitinib [70 vs 56 percent; p=0.008], and the median duration of response was 10.1 and 8.4 months, respectively. The OS data are not mature as yet.”
Treatment discontinuation rate was similar for both study arms at about 6 percent. Common grade ≥3 adverse events were diarrhoea, rash and acne with afatinib, and raised alanine aminotransferase with gefitinib.
“The improvement in PFS became more pronounced over time with a significantly higher proportion of patients on afatinib being progression-free at 18 months [27 vs 15 percent; p=0.018] and 24 months [18 vs 8 percent; p=0.018], showing a greater long-term benefit,” he noted.
“Unlike the first-generation EGFR inhibitor gefitinib, the irreversible ErbB family blocker afatinib is suggested to be active in prolonging tumour response and delaying disease progression,” commented discussant Dr. Egbert Smit of the Netherlands Cancer Institute in Amsterdam, The Netherlands. “While these data suggest afatinib may be the preferred first-line treatment for advanced NSCLC, we also need to consider the different tolerability profiles of gefitinib and afatinib. The selection of therapy will still be based on individual clinical decision.”