Post-progression afatinib exposure boosts NSCLC outcomes
medwireNews: Continued exposure to afatinib plus paclitaxel can benefit non-small-cell lung cancer (NSCLC) patients who developed resistance to erlotinib or gefitinib and progressed after initially responding to afatinib monotherapy, suggest phase III trial results.
“This is the first prospective evidence to support the concept for maintaining target inhibition beyond formal disease progression in oncogene-addicted lung cancer”, say Martin Schuler, from University Hospital Essen in Germany, and fellow LUX-Lung 5 investigators in the Annals of Oncology.
The trial included 202 patients with stage IIIB or IV NSCLC who had failed one or more lines of chemotherapy and had progressed after deriving at least 12 weeks of clinical benefit on erlotinib or gefitinib and thereafter with afatinib monotherapy.
The primary endpoint of progression-free survival was significantly longer for the 134 patients randomly allocated to receive afatinib plus paclitaxel than for the 68 patients treated with investigator’s choice of single-agent chemotherapy, at a median of 5.6 versus 2.8 months, giving a hazard ratio of 0.60.
Treatment with the irreversible ErbB family inhibitor plus paclitaxel also significantly improved the clinical benefit rate (74.5 vs 45.6%) and objective response rate (32.1 vs 13.2%) compared with chemotherapy alone.
But median overall survival was identical for the treatment arms, at 12.2 months, which the team did not find surprising given the imbalance between groups with respect to the number of post-progression treatments. Specifically, fewer patients in the afatinib than the chemotherapy arm received two further lines of therapy (15 vs 36%).
Side effects of grade 3 and higher were observed in 48.5% of patients in the combination group and 30.0% of those in the chemotherapy group, with diarrhoea (12.1%), neutropenia (11.3%) and asthenia (8.3%) the most common high-grade toxicities in the afatinib plus paclitaxel arm.
Treatment-related serious adverse events occurred in 11.4% of afatinib-treated patients, compared with 3.3% of those given chemotherapy. And the corresponding discontinuation rates were 18.9% and 6.7%.
However, the researchers note that global health status and health-related quality-of-life were comparable between groups, despite the differences in frequency and severity of adverse events between arms and a “doubling of median treatment time” with afatinib versus chemotherapy (133 and 51 days, respectively).
They also comment that the toxicity profile of afatinib plus paclitaxel was consistent with previous reports.
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