Afatinib shows improvement in overall survival in lung cancer patients whose tumors have the most common EGFR mutation: Study

Dr SequistPatients with advanced non-small cell lung cancer (NSCLC) whose tumors have the most common epidermal growth factor receptor (EGFR)  mutation (exon 19 deletion) lived longer if treated with first-line afatinib (Gilotrif) compared to chemotherapy, according to data presented at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO), in Chicago.

Treatment-naïve patients with EGFR mutations stage IIIB/IV NSCLC were randomized 2:1 to afatinib 40 mg orally once daily, or up to 6 cycles of pemetrexed/cisplatin in LUX-Lung 3 (n=345), or up to 6 cycles of gemcitabine/cisplatin in LUX-Lung 6) (n=364). The primary end point was progression-free survival (PFS), with overall survival (OS) as a secondary end point. LUX-Lug 3 and LUX-Lung 6 are 2 of the largest trials in this patient population.

The study was sponsored by Boehringer Ingelheim.

Afatinib prolonged survival of lung cancer patients whose tumors have common EGFR mutations compared with standard chemotherapy by a median of 3 months (27.3 to 24.3 months) and significantly reduced the risk of death by 19% (HR=0.81, P=.037). The most pronounced reduction in risk of death was 41% (HR=0.59, CI 0.45, 0.77) in patients whose tumors have the most common EGFR mutation (exon 19 deletion of the EGFR gene); for patients with the exon 21 (L8585R) mutation there was no impact on overall survival (HR=1.25, CI 0.92, 1.71). Exon 19 deletions occur with a frequency of approximately 48% in EGFR-mutant lung tumors. See abstract (#8004) for more.

The analysis of the delay in tumor growth (progression-free survival) and adverse events associated with afatinib in comparison with standard chemotherapy were consistent with previously published results of the primary data from these 2 trials.

“Multiple phase 3 studies have compared various EGFR inhibitors to chemotherapy and all have shown improved response rates and progression-free survival compared to chemo, which has set the modern paradigm of treatment to selection by genotype,” said Lecia Sequist, MD, MPH, medical oncologist at the Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School.

“However, none of the other studies have shown a survival benefit; these are the first to do so. It is interesting to contemplate why these studies were positive for survival and the others were not, and at this time we don’t fully know the reason(s),” Dr Sequist said. “These are some of the largest such trials to be done and may have been better powered to demonstrate the difference. They are also the only trials done with afatinib, a second-generation pan-HER inhibitor, which may be an important factor.

The results across studies now clearly support that EGFR mutants should be treated with a first-line EGFR TKI, according to Dr Sequist. “We have seen better responses and PFS across the board and now OS in the LUX-Lung studies with afatinib, especially among patients with exon 19 deletion mutations. All adenocarcinoma lung cancer patients around the world should be genotyped at the time of diagnosis so that those with EGFR mutations can receive EGFR inhibitors early.”

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 one of the 2 most common EGFR mutations (exon 19 deletions or exon 21 L858R).