“The LUX-Lung 3 study has been much awaited. It is the first study to use cisplatin/pemetrexed [Alimta], which we now recognize as the best comparator arm. The study was positive for afatinib. While the use of maintenance pemetrexed may have dented the hazard ratio, I doubt this would have impacted on the result,” said formal discussant of this trial, Benjamin J. Solomon, MBBS, PhD, Peter MacCallum Cancer Centre, East Melbourne, Australia.

“Even though the efficacy [of afatinib] comes at a cost related to toxicity, the investigators seem to have come up with ways to manage the toxicities [diarrhea, rash, stomatitis, paronychia, dry skin], because there were lower rates of discontinuation in the afatinib arm,” he noted.

“Afatinib is now another proven option for EGFR-positive lung cancer patients, alongside erlotinib and gefitinib. LUX-Lung 3 can be added to the list of positive first-line studies in this population. This is the best progression-free survival data reported so far in patients with common mutations. We can’t make direct comparisons of these results with other studies because they had different comparator arms,” Dr. Solomon cautioned. LUX-Lung 7 is a planned head-to-head comparison of afatanib vs gefitinib in patients with common EGFR mutations.

“As impressive as progression-free survival is with afatinib, all patients will eventually develop acquired resistance to this family of drugs. To push progression-free survival even further than 13 months, we need to find other options,” he stated.

Dr. Solomon said he would be interested in the outcome with afatinib in patients with less common mutations. Preliminary data suggest that afatinib plus cetuximab (Erbitux) may overcome resistance associated with the T790M mutation in patients with NSCLC. Another emerging approach is use of third-generation mutation-specific inhibitors, Dr. Solomon said.

“The next generation of EGFR inhibitors has arrived. But it is premature to say goodbye to the older generation,” he commented. ■

Disclosure: Dr. Solomon has served as consultant or advisor for AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Lilly, Pfizer, and Roche.