by ecancer reporter Janet Fricker

Patients with late stage non-small cell lung cancer (NSCLC) already treated with the EGRF inhibitors erlotinib or gefitinib gained further progression free survival benefits and tumour shrinkage when treated with afatinib, reported the LUX-Lung 1 trial at the European Society of Medical Oncology (ESMO) meeting in Milan, Italy, 8-12 October, 2010. The study, presented in the Presidential Symposium, however, showed no benefit for the primary endpoint of overall survival.

Lung cancer remains an area of high unmet need, especially in the advanced stages where it is particularly aggressive and patients have limited treatment options. Currently there are no FDA approved therapies for patients with advanced lung cancer who have failed chemotherapy and progressed after treatment with an EGFR TKI.  Afatinib is an  investigational orally administered irreversible inhibitor of  two cancer-associated cell surface molecules – epidermal growth factor receptor (EGFR) and human growth factor receptor 2 (HER2).

In the phase IIb/III study, 585 patients with advanced NSCLC who had received chemotherapy and a prior EGFR tyrosine kinase inhibitor (gefitinib or erlotinib) were randomly assigned 2:1 to receive best supportive care plus placebo or supportive care plus afatinib.

Results show that median overall survival was 11.96 months for the placebo group versus 10.78 months for the afatinib group (HR 1.08, 95% CI 0.86 to 1.35).  However, the secondary end point of progression free survival was 1.1 months for the placebo group versus 3.3 months for the afatinib group (HR 0.38, 95% CI 0.31 to 0.48, p<0.0001). At 8 weeks  58% of patients receiving afatinib showed disease control (including stable disease and tumour shrinkage) versus 19% taking placebo( p<0.001). The two most common side effects with afatinib were diarrhoea and rash which could be managed effectively by dose interruption/reduction.

“Our study showed that adding afatinib to best supportive care improved progression-free but not overall survival as compared to placebo and best supportive care in patients with advanced non-small cell lung cancer who previously received chemotherapy and either gefitinib or erlotinib,” said Dr

Vincent Miller from Memorial Sloan-Kettering Cancer Center, New York, USA. “The fact that afatinib induced objective regressions in a population with no or limited treatment options, delayed progression of cancer and was associated with some improvements in cancer-related symptoms cannot be minimised,” he added.