Afatinib ‘first line’ for advanced mutation-positive lung cancer

By Lynda Williams, Senior medwireNews Reporter

Afatinib should be given as a first-line treatment for Asian patients with advanced, epidermal growth factor receptor (EGFR) mutation-positive, non-small-cell lung cancer (NSCLC), researchers recommend.

LUX-Lung 6 study results indicate that treatment-naïve patients given the irreversible ErbB family blocker afatinib for stage III or IV disease had significantly better median progression-free survival (PFS) than those given gemcitabine plus cisplatin, at 11.0 versus 5.6 months and a hazard ratio of 0.28.

The 242 patients given afatinib were also significantly more likely to achieve an objective response to treatment than the 122 patients given the combined chemotherapy (66.9 vs 23.0%) and had a more sustained response to treatment (9.7 vs 4.3 months), report Yi-Long Wu (Guangdong Lung Cancer Institute, Guangzhou, China) and co-authors.

Afatinib-treated patients were also significantly more likely to experience improvements in symptoms such as cough, dyspnoea and pain than controls, as well as gains in overall health and quality of life, they write in TheLancet Oncology.

Moreover, afatinib was associated with a lower rate of grade 3 and above treatment-related adverse events than chemotherapy (36.0 vs 60.2%) and a reduced rate of treatment discontinuation due to side effects (5.9 vs 39.8%).

The most common adverse events with afatinib were diarrhoea, skin complaints and stomatitis or mucositis, whereas vomiting, nausea, neutropenia and leucopenia were most common with combined chemotherapy.

“The improvement in progression-free survival – combined with improvements in quality of life – suggests that clinicians should consider afatinib as a standard first-line treatment option for patients with EGFR mutation-positive [NSCLC],” Wu et al therefore conclude.

LUX-Lung 6 results, viewed alongside the LUX-Lung 3 results for afatinib versus cisplatin plus pemetrexed, should “end debate” about whether patients should begin treatment with an EGFR tyrosine kinase inhibitor (TKI) or chemotherapy, write Marina Garassino (IRCSS Istituto Nazionale dei Tumori, Milan, Italy) and Valter Torri (IRCCS Mario Negri, Milan, Italy) in an accompanying editorial.

However, noting that PFS was not significantly improved with afatinib in the study among a subgroup of 40 patients with rare EGFR mutations, they suggest that further research is required to demonstrate efficacy in this population.

Research is also required to demonstrate afatinib efficacy in non-Asian patients, the commentators write, adding that LUX-Lung 7 and 8 results comparing afatinib against erlotinib and gefitinib, respectively, must be published before the best TKI is known.

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