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Boehringer Ingelheim have announced promising results from two clinical trials of its investigational cancer compound afatinib (BIBW 2992) presented at the 35th European Society for Medical Oncology (ESMO) Congress in Milan, Italy.
Results from the â€œLUX-Lung 1â€ trial suggest that afatinib (BIBW 2992) is highly active in late-stage patients with NSCLC1, while in the LUX-Lung 2 phase II trial afatinib demonstrated encouraging activity in advanced NSCLC patients that have a mutated EGF Receptor.
Afatinib, which is taken as a tablet, is a next generation inhibitor of the epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2) tyrosine kinase (TK) and unlike first generation TKIs irreversibly binds to EGFR/HER2. The compound is under development in several solid tumour types.
The LUX-Lung 1 trial (phase II b/III) compared afatinib to placebo in over 580 patients with advanced NSCLC whose disease has progressed after receiving chemotherapy and a first-generation EGFR Tyrosine Kinase Inhibitor (gefitinib or erlotinib) â€“ results showed:
Even though the LUX-Lung 1 trial did not meet the primary endpoint of prolonging overall survival (OS), afatinib significantly extended the time before the tumour progressed; specifically it led to a three-fold extension of progression-free survival (PFS, key secondary endpoint) from 1.1 months to 3.3 months over placebo.
The PFS benefit was apparent as a robust effect across all patient subgroups and has been confirmed by independent review.
There was a significantly higher rate of tumour control or shrinkage in those patients who took afatinib (disease control rate: 58%) versus those taking placebo (disease control rate: 19%); also independently verified.
Afatinib significantly improved the lung-cancer related symptoms cough, dyspnea (shortness of breath) and pain, and delayed the time to deterioration of cough, individual dyspnea items and chest pain significantly.
There were no new or unexpected safety findings; the main side effects were diarrhea and rash.
The results of LUX-Lung 1 in a special patient population whose cancers probably have a high incidence of EGFR mutations have substantially contributed to better understanding of the biology of these tumours. Conclusions from the trial will be relevant for the design of further clinical studies, which will evaluate further patient populations and their mutation status.
Lung cancer is the most common and most deadly form of cancer in the world, accounting for 1.6 million new cancer cases annually and 1.4 million deaths from lung cancer. Lung cancer remains an area of high unmet need, especially in its advanced stages where it is particularly aggressive and patients have limited treatment options. No approved therapy is currently available for patients with advanced lung cancer who have failed chemotherapy and progressed after treatments with EGFR TKI.
â€œIn clinical practice, it is of high relevance to patients to have improvement in key lung cancer related symptoms such as cough, shortness of breath and painâ€ commented Dr Vera Hirsh, investigator of the trial, and Chair of the Lung Cancer Committee, McGill University, Canada. â€œFurthermore, the time to deterioration, meaning the time before the symptoms get worse, was significantly extended for some of these symptoms in the LUX Lung 1 study.â€
This is the first time that a compound has demonstrated in a controlled study, a clinically meaningful improvement in PFS in patients with NSCLC who have progressed on first generation EGFR TKIs.
Encouraging results were also presented for LUX-Lung 2, a phase II trial studying patients with advanced NSCLC who harbour EGFR mutations. This result shows that the use of afatinib led to a high rate of tumour size reduction (overall response rate of 61%) and a long delay in the progression of cancer by over 1 year (PFS of 14 months). These results help to underline afatinibâ€™s potential benefit as a first or second line treatment in patients with EGFR mutations. Two phase III trials, LUX-Lung 3 and LUX-Lung 6 are currently underway to further evaluate afatinib as a first-line treatment in this patient group.
â€œBoth of these recent trials demonstrate the promise of afatinib as a next-generation treatment option in NSCLC patients in different settingsâ€ says Prof Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. â€œWe are convinced that afatinib could provide a benefit for patients with NSCLC, and we remain fully committed to its ongoing development in lung cancer and in other solid cancer types.â€