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Lung cancer: Phase III data for Gilotrif (afatinib) published in The Lancet Oncology

has announced overall survival (OS) results were published in The Lancet Oncology from two independent Phase III clinical trials (LUX-Lung 3 and LUX-Lung 6) in epidermal growth factor receptor () mutation-positive patients with metastatic non-small cell (NSCLC). In each trial, patients whose tumors have the most common mutation (deletion in exon 19; Del19) lived more than one year longer when treated with first-line afatinib compared to standard chemotherapy. Afatinib is the first and only inhibitor to demonstrate an overall survival benefit compared to chemotherapy in the first-line treatment of NSCLC patients with mutations.

“Lung cancer patients with this specific genetic mutation experienced a meaningful one-year survival benefit when they were randomized to first-line therapy with afatinib compared to chemotherapy,” said Lecia V. Sequist, M.D., MPH, medical oncologist at Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School. “These data provide important evidence about the use of afatinib in patients whose tumors have the Del19 mutation and tell us that the standard treatments and approaches should no longer be assumed equivalent for every EGFR mutation.”

Results from both trials showed similar OS in the afatinib and chemotherapy arms in the overall NSCLC EGFR mutation-positive population (LUX-Lung 3: median OS 28.2 to 28.2 months, HR 0.88; p=0.39); (LUX-Lung 6: median OS 23.1 to 23.5 months, HR 0.93; p=0.61). However, a pronounced benefit was observed in patients with the Del19 mutation. Both studies individually demonstrated a reduction in risk of death with first-line afatinib compared to chemotherapy in patients whose tumors have the Del19 mutation. That translated into a survival benefit of more than a year (LUX-Lung 3: median OS 33.3 to 21.1 months; HR 0.54; p=0.0015); (LUX-Lung 6: median OS 31.4 to 18.4 months; HR 0.64; p=0.0229).

The effect was not observed for patients whose tumors have the L858R mutations as survival did not differ between treatment arms in each trial (LUX-Lung 3: HR 1.30; p=0.29); (LUX-Lung 6: HR 1.22; p=0.34).

“We are proud to have these results published in The Lancet Oncology to provide further insights into the role of afatinib as first-line treatment for patients with specific mutation types,” commented Berthold Greifenberg, M.D., vice president, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc. “These findings reinforce the importance of identifying the specific mutation types to help improve outcomes for patients with EGFR mutation-positive lung cancer.”

LUX-Lung 3 (Global) and LUX-Lung-6 (Asian), two of the largest trials in this patient population, were similar in design with the exception of the platinum-based chemotherapy comparator regimen: pemetrexed/cisplatin in LUX-Lung 3 and gemcitabine/cisplatin in LUX-Lung 6. Both studies met the primary endpoint of progression-free survival for the group of patients whose tumors have common EGFR mutations receiving first-line afatinib. The most common adverse events (grade 3 and 4) associated with afatinib in comparison with chemotherapy included rash/acne, diarrhea, paronychia and stomatitis/mucositis, which were previously published with the primary data from these two trials.