subject: Afatinib (BIBW 2992*) Triples Progression Free Survival in Lung Cancer Patients [print this page] Boehringer Ingelheim 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 LUX-Lung 1 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) results showed1:
* 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 deaths2 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.
In 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 pain? commented Dr Vera Hirsh, investigator of the trial, and Chair of the
Lung Cancer Committee, McGill University, Canada. Furthermore, 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.
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)3.
These results help to underline afatinib?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
