Tolerability-guided dose adjustment is an effective measure to reduce afatinib (Giotrif)-related adverse events (AEs) without affecting therapeutic efficacy in patients with non–small cell lung cancer (NSCLC), according to results from a new post-hoc analysis of two large phase 3 trials. The findings were published online in Annals of Oncology.
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LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, phase 3 trials of afatinib vs chemotherapy as first-line treatment for patients with epidermal growth factor receptor mutation-positive, advanced, and metastatic NSCLC. Patients were randomized 2:1 to oral afatinib 40 mg/d or up to six cycles of cisplatin-based chemotherapy. Afatinib-treated patients from LUX-Lung 3 (n=229) and LUX-Lung 6 (n=239) trials were included in the new analysis. The incidence and severity of common AEs before and after afatinib dose reduction were assessed.
Dose reductions occurred in 53.3% (n=122) and 28% (n=67) of patients in LUX-Lung 3 and LUX-Lung 6, respectively; most within the first 6 months of treatment (86.1% and 82.1%, respectively). Dose escalation occurred in 7% (n=16) and 15.9% (n=38) of patients in each study, respectively. Dose reductions led to a decreases in the incidence and severity of treatment-related AEs in both trials. Treatment-related AEs decreased 86.1% with fewer patients (20.5%) experiencing grade ≥3 treatment-related AEs in the LUX-Lung 3 cohort; in LUX-Lung 6 cohort, 50% of patients experienced treatment-related AEs and only 11.9% experienced grade ≥3 treatment-related AEs. Median progression-free survival was similar in patients who dose reduced within the first six months of treatment vs those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).
This new analysis suggests that dosing of afatinib can be adjusted to help manage treatment-related AEs without affecting efficacy, allowing patients to continue effective therapy while obtaining clinical benefit, concluded the researchers.—Eileen Koutnik-Fotopoulos
