LUX-Lung 8 supports afatinib in squamous NSCLC

By Shreeya Nanda, Senior medwireNews Reporter

Compared with erlotinib, treatment with afatinib leads to outcomes in previously treated patients with advanced squamous non-small-cell lung cancer (NSCLC), suggest the results of a head-to-head trial.

“These data support the addition of afatinib to the armamentarium of treatments for this difficult-to-treat population,” say the LUX-Lung 8 researchers in The Lancet Oncology.

In the trial, patients with stage IIIB or IV squamous NSCLC who had failed platinum-based chemotherapy were randomly assigned to receive either the irreversible pan-ErbB tyrosine kinase inhibitor (TKI) afatinib or the epidermal growth factor receptor (EGFR) TKI erlotinib and followed up for a median of 18.4 months.

Median overall survival was 7.9 months for the 398 afatinib-treated patients and 6.8 months for the 397 erlotinib-treated patients, a significant difference with a hazard ratio (HR) for death of 0.81.

And the difference between the afatinib and erlotinib arms remained significant at 6 months, 12 months and 18 months, with estimated overall survival rates of 63.6% versus 54.6%, 36.4% versus 28.2% and 22.0% versus 14.4%, respectively.

Progression-free survival was also significantly improved in the afatinib compared with the erlotinib group, at a median of 2.6 versus 1.9 months, as was the rate of disease control, at 51% versus 40%. And the difference in objective response rate between the groups tended towards significance, favouring the afatinib group (6.0 vs 3.0%).

Adverse events of grade 3 or above were observed in 57% of patients given afatinib and in the same proportion of those given erlotinib. There was a higher incidence of grade 3 or 4 diarrhoea and stomatitis in afatinib- than in erlotinib-treated patients while the latter were more likely to experience rash or acne.

“Whether the 1.1 month improvement in median overall survival noted with afatinib is clinically significant could be debated, but it was encouraging that longer-term survival at 12 months and 18 months was significantly improved with afatinib”, observe Jean-Charles Soria (Gustave Roussy Cancer Campus and University Paris-Sud, France) and colleagues.

“In one of the most genetically complex and difficult-to-treat human cancers, these improvements can be clinically important.”

In a related comment, Fred Hirsch (University of Colorado Cancer Center, Aurora, USA) and co-authors highlight the importance of “clinical judgment” with regard to the continued role of EGFR TKIs in squamous NSCLC treatment in light of treatments for newer molecular targets, such as programmed death 1.

“If a new treatment achieves the ultimate goal of extending survival, and if that benefit is accompanied by symptom relief and acceptable toxic effects, we think that some physicians and patients will choose this option, if it is available”, they write.

“To turn lung cancer into a chronic disease, sequential lines of treatment will be necessary, with both physician and patient reviewing the available options and selecting from among them at each treatment decision.

“To undervalue the importance of improved survival in LUX-Lung 8 would limit these options.”

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