Boehringer Ingelheim announced new overall survival results from a post-hoc analysis combining the data of two Phase 3 trials (LUX-Lung 3 and LUX-Lung 6). The analysis showed patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or exon 21 [L858R] substitutions) lived longer if treated with first-line afatinib compared to chemotherapy.
An oral presentation at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), will discuss these data in more depth, providing further insights into their impact on clinical practice and patient care. Data from six other abstracts involving afatinib and other compounds in Boehringer Ingelheim’s oncology portfolio, will also be presented or published at ASCO.
In the combined analysis from two of the largest trials in this patient population, afatinib prolonged survival of lung cancer patients whose tumors harbor common EGFR mutations compared with standard chemotherapy by a median of 3 months (27.3 compared to 24.3 months), significantly reducing the risk of death by 19%. The most pronounced reduction in risk of death, by 41%, was noted for patients whose tumors have the most common type of EGFR mutation (deletion in exon 19 of the EGFR gene). The conclusions of this analysis further substantiate earlier published results on delay in tumor growth (progression-free survival), better control of lung cancer symptoms and adverse events associated with afatinib in comparison with standard chemotherapy.
Commenting on the overall survival results, principal investigator Professor James Chih-Hsin Yang, National Taiwan University Hospital in Taiwan, said: “The results of two afatinib trials independently show for the first time that despite cross-over in subsequent treatment, front-line use of a targeted treatment can prolong overall survival in patients with deletion 19 EGFR mutation-positive lung cancer compared to chemotherapy. The results add to the list of benefits already shown in these studies, which include improvements in tumor shrinkage, longer duration of disease control and in life-restricting, disease-related symptoms such as cough, pain and shortness of breath.”
Another Phase 3 study in lung cancer patients (LUX-Lung 5), also to be presented at ASCO, met its primary endpoint by showing the advantage of continuing treatment with afatinib, in combination with chemotherapy, after the tumor started to grow on afatinib alone (treatment beyond progression). This Phase 3 study compared afatinib with paclitaxel (a chemotherapy) versus investigator’s choice of chemotherapy alone in patients with late-stage lung cancer after failure of several treatments, including chemotherapy, erlotinib or gefitinib and afatinib alone.
Those patients who continued afatinib treatment with the addition of chemotherapy, after progressing on afatinib alone, had a further delay in tumor growth compared to the group who stopped afatinib treatment, and received chemotherapy only (tumor growth was delayed by 5.6 months and 2.8 months respectively). This corresponded to a 40% reduction in risk of disease progression. The most common adverse events in patients treated with afatinib and chemotherapy combination were diarrhea (often associated with EGFR inhibition), hair loss (alopecia) and weakness (asthenia– often associated with chemotherapy).
Professor Martin Schuler, West German Cancer Center at the University Hospital Essen, Germany, principal investigator commented: “These results indicate the potential of a new approach for these difficult-to-treat patients– the continuation of afatinib treatment with the addition of chemotherapy, even after previous EGFR TKI treatment has failed and tumors have started to grow again.”
Professor Klaus Dugi, chief medical officer, Boehringer Ingelheim, commented: “Lung cancer is not just one disease, and we are proud to be conducting research on afatinib in a variety of treatment settings that may ultimately expand treatment options for patients. The combined and individual overall survival results of LUX-Lung 3 and LUX-Lung 6, together with our existing previously reported quality of life and patient reported outcome data, contribute significantly to the robust body of evidence for the use of first-line afatinib in EGFR mutated lung cancer.”
Afatinib (GIOTRIF/GILOTRIF) is indicated for the treatment of distinct types of EGFR mutation-positive NSCLC. Afatinib is approved in a number of markets, including the EU, Japan, Taiwan and Canada under the brand name GIOTRIF and in the United States under the brand name GILOTRIF. It is under regulatory review in other countries. Phase 3 trials in squamous head and neck cancer (HNSCC) and trials in other tumor types are ongoing.
Date: May 15, 2014
Source: Boehringer Ingelheim