Overall survival extended in afatinib-treated patients with specific lung cancer mutations

Dr Sequist

Afatinib extends overall survival in lung cancer patients whose tumors have the most common epidermal growth factor receptor (EGFR) mutation compared with chemotherapy, according to study results published in The Lancet Oncology from 2 independent phase 3 clinical trials in EGFR mutation-positive patients with metastatic non-small cell lung cancer (NSCLC).

In some people, genetic mutations lead to the constant activation of the EGFR protein, which is associated with uncontrolled cell division and the development and progression of NSCLC. Among patients diagnosed with NSCLC, the most common form of lung cancer, it is estimated that between 10% and 15% of Caucasians and approximately 40% of Asians have EGFR mutations, which in 90% of cases are either Del19 or L858R mutations.

This study looked at the long-term survival outcomes of 2 separate but similarly designed phase 3 randomized clinical trials, the Lux-Lung 3 and the Lux-Lung 6 studies. Each trial enrolled patients with newly diagnosed advanced lung cancer and EGFR mutations and randomly assigned them to either receive first-line therapy with the EGFR inhibitor afatinib or combination chemotherapy (cisplatin/pemetrexed in LL3 and cisplatin/gemcitabine in LL6).

In each trial, patients whose tumors have the most common EGFR mutation (deletion in exon 19; Del19) lived more than 1 year longer when treated with first-line afatinib compared to standard chemotherapy. Afatinib is the first EGFR inhibitor to demonstrate an overall survival benefit compared to chemotherapy in the first-line treatment of NSCLC patients with EGFR mutations.

“Overall survival was not significantly different by treatment arm for the overall study population, which is what was expected as all previous similar trials with earlier EGFR inhibitors showed no survival benefit with erlotinib or gefitinib, only progression-free survival [PFS] benefit,” said Lecia V. Sequist, MD, MPH, medical oncologist at Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School.

When the researchers examined the most common EGFR mutation, exon 19 deletion mutations, a significant survival advantage was noted for the afatinib patients, according to Dr Sequist.

In LUX-Lung 3, median overall survival was 33.3 months in the afatinib group versus 21.1 months in the chemotherapy group (HR 0·54, 95% CI 0·36–0·79, P=.0015); in LUX-Lung 6, it was 31.4 months versus 18.4 months, respectively (HR 0.64, 95% CI 0·44–0·94, P=.023). There was no difference in survival for the other major mutation subset, the L858R mutations.

“The take-away message is that afatinib appears to have not only a PFS advantage for EGFR mutatations  compared to chemotherapy, but among those with the exon 19 deletion EGFR mutation, there is also an impressive survival advantage,” Dr. Sequist said.

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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 2 trials.

The study was funded by Boehringer Ingelheim.