Boehringer Ingelheim announces results from afatinib clinical trials at 35th ESMO

Oct 11 2010

Boehringer Ingelheim Pharmaceuticals, Inc. announced today results from two clinical trials for its investigational cancer compound afatinib (BIBW 2992) presented at the 35th European Society for Medical Oncology (ESMO) Congress in Milan, Italy.  In the phase IIb/III LUX-Lung 1 study, afatinib tripled the secondary endpoint of progression free survival (PFS) but did not extend the primary endpoint of overall survival (OS) in late-stage patients with non-small cell lung cancer (NSCLC).  

Afatinib is an investigational orally administered irreversible inhibitor of both the epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2) tyrosine kinases.  Afatinib is under development in several solid tumors including NSCLC, breast and head and neck cancer.

The LUX-Lung 1 trial compared afatinib to placebo in over 580 patients with advanced NSCLC who had received chemotherapy and a prior EGFR tyrosine kinase inhibitor (EGFR TKI; gefitinib or erlotinib); results show:

• Afatinib did not improve OS compared to placebo – 10.78 months vs. 11.96 months, respectively (HR = 1.08, 95% CI 0.86 to 1.35)
• As a secondary endpoint, afatinib extended PFS three-fold compared to placebo (3.3 months vs. 1.1 months) (HR = 0.38, 95% CI 0.31 to 0.48, p<0.0001).  The improvement in PFS was apparent across all patient subgroups and has been confirmed by independent review
• At 8 weeks, there was a significantly higher disease control rate (stable disease and tumor shrinkage) in those patients who took afatinib (58%) vs. those taking placebo (19%), which was also independently verified (p<0.0001)
• Improvement of the lung cancer-related symptoms of cough, dyspnea and pain was observed in the afatinib arm vs. placebo.  In addition, the time to deterioration of cough, individual dyspnea items and chest pain was longer in the afatinib arm
• The two most common side effects associated with treatment with afatinib were diarrhea (87% all grades, with 17% Grade 3) and rash/acne (79% all grades, with 14% Grade 3).  These side effects were usually well-managed by supportive care and dose reduction

It is important to note that the overall study population, which included patients who received chemotherapy and one line of treatment with a first-generation EGFR inhibitor for at least 12 weeks, had a better performance status and lived longer than originally anticipated for patients with advanced NSCLC.  This information warrants further investigation of subpopulations in treatment of advanced NSCLC.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.