INGELHEIM, Germany--(BUSINESS WIRE)--For non U.S. Media Only
Boehringer Ingelheim today announced data from two separate Phase III clinical trials, involving investigational oncology compounds with a different mode of action – afatinib* and nintedanib* – in two distinct populations of patients with advanced non-small cell lung cancer (NSCLC).
The LUX-Lung 6 trial results show that patients with epidermal growth factor receptor (EGFR or ErbB1) mutation-positive advanced NSCLC treated first-line with afatinib* lived for almost a year before their tumour started to grow again (progression-free survival, or PFS) compared with just under half a year for patients treated with chemotherapy. In addition, 47 percent of afatinib*-treated patients are alive and progression-free after one year of treatment compared to only 2 percent on chemotherapy. Tumour shrinkage induced by afatinib* translated into improvements in disease-related symptoms. Patients´ global health-related quality of life (QoL) was significantly improved with afatinib* compared to chemotherapy.1 The delay in tumour growth in the LUX-Lung 6 trial compares well with data from the registration trial LUX-Lung 3, substantiating the efficacy of afatinib* and the robustness of the data.
The LUME-Lung 2 trial evaluated the triple angiokinase inhibitor nintedanib* in combination with chemotherapy pemetrexed in patients with advanced NSCLC after initial chemotherapy has failed. The trial did not pass the pre-defined interim analysis from external independent experts and was prematurely halted. However, the final results showed a significant improvement of the primary endpoint, centrally assessed PFS.2
Overall, both afatinib* and nintedanib* significantly improved PFS, the primary study endpoints, in their respective study populations. The most common grade 3 adverse events (AEs) associated with afatinib* in LUX-Lung 6 were diarrhoea, rash and stomatitis/mucositis (inflammation of the mouth and throat). These side effects are as expected with EGFR inhibition, consistent with previous studies, and were predictable, manageable and reversible. The most common adverse events in LUME-Lung 2 were gastrointestinal side effects, mostly of mild or moderate intensity, and manageable with supportive treatment, and liver enzyme elevations which were reversible upon dose reduction or if needed in rare cases discontinuation. Full data will be presented at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, May 31-June 4, 2013.
“NSCLC is a complex disease with a high mortality rate and an area of oncology where advancements are necessary to improve outcomes for patients. The positive findings from these Phase III trials demonstrate the importance of exploring new treatment approaches tailored for the various NSCLC populations,” said Dr. Nick Thatcher, Christie Hospital, University of Manchester, UK.
The LUX-Lung 6 Clinical Trial of Afatinib*
LUX-Lung 6 (Efficacy) Abstract: #8016
Poster Discussion: Sunday, June 2, 11:30 AM-12:30 PM, poster board #5
The LUX-Lung 6 trial is the largest prospective Phase III trial conducted to date in the EGFR mutation-positive advanced NSCLC patient population. The trial evaluated afatinib* (n=242) compared to standard chemotherapy (gemcitabine and cisplatin) (n=122) as a first-line treatment in 364 Asian patients with EGFR mutation-positive advanced NSCLC.1
Results showed the trial met its primary endpoint of PFS as assessed by independent central review; within the general study population, patients treated with afatinib* lived for a median of 11.0 months before their tumour started to grow again (PFS) versus 5.6 months for those chemotherapy-treated patients (HR=0.28, p<0.0001).1 The PFS findings were consistent across all subgroups. Results from the investigator review were similar with a median improvement in PFS of 13.7 months with afatinib* compared to 5.6 months with chemotherapy (HR=0.26, p<0.0001).1
Secondary efficacy endpoints included objective response rate (ORR: proportion of patients with considerable tumour size reduction as predefined by response evaluation criteria) and disease control rate (DCR: proportion of patients who have achieved complete response, partial response and stable disease3). Results showed that patients treated with afatinib* experienced significantly higher ORR (66.9 vs. 23.0%, p<0.0001) and DCR (92.6 vs. 76.2%, p<0.0001) compared to patients treated with chemotherapy.1
The most common grade 3 adverse events (AEs) associated with afatinib* in LUX-Lung 6 were diarrhoea, rash and stomatitis/mucositis (inflammation of the mouth and throat). These side effects are as expected with EGFR inhibition, consistent with previous studies, and were predictable, manageable and reversible. The most common AEs associated with chemotherapy were neutropenia (an abnormally low level of neutrophils, a type of white blood cell), vomiting and leukopenia (a decrease in the number of white blood cells). The discontinuation rate due to AEs related to treatment was 5.9 percent of patients on the afatinib* arm and 39.8 percent of patients on the chemotherapy arm. Importantly only 2 percent of patients on afatinib* decided to discontinue due to rash and none for diarrhoea.1
LUX-Lung 6 (Patient-Reported Outcomes) Abstract: #8061
Poster: Saturday, June 1, 8:00-11:45 AM, poster board #35A
Patient-reported outcomes (PROs) were evaluated as secondary endpoints of the LUX-Lung 6 trial. Based on the reported outcomes, the improvement in PFS seen with afatinib* was associated with significantly better health-related QoL and significantly longer control of life-restricting lung cancer-related symptoms compared with chemotherapy.4
Health-related QoL was measured using the EORTC QLQ-C30 questionnaire, which evaluated global health status/QoL (overall well-being) in addition to physical, cognitive, role, social and emotional functioning. Based on review of these six measurements, afatinib*-treated patients experienced improvements in their global health-related QoL and physical, role and social functioning compared to chemotherapy (p<0.05).4
“The data to be presented from the LUX-Lung 6 trial show a meaningful improvement in progression-free survival with first-line afatinib* treatment for patients with EGFR mutation-positive advanced non-small cell lung cancer,” said Prof Yi-Long Wu from the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangong Academy of Medical Sciences, Guangzhou, China and principal investigator of the LUX Lung 6 trial. “This is now the second largest Phase III trial involving afatinib* to confirm a high level of activity accompanied by improved health-related quality of life in this patient population.”
The LUME-Lung 2 Clinical Trial of Nintedanib*
LUME-LUNG 2 (Efficacy) Abstract: #8034
Poster Discussion: Sunday, June 2, 11:30 AM-12:30 PM, in E354a, poster board #23
This study evaluated nintedanib* plus pemetrexed (n=353) compared to pemetrexed plus placebo (n=360) in 713 patients with advanced non-squamous NSCLC who relapsed after, first-line chemotherapy.2 Although prematurely halted, the trial showed a significant improvement in centrally assessed PFS, the primary endpoint of the trial; within the general study population, patients treated with nintedanib*/pemetrexed lived for a median of 4.4 months before their tumour started to grow again, compared to 3.6 months for patients assigned to the pemetrexed/placebo arm (HR=0.83, p=0.04).
The combination of nintedanib* and pemetrexed was not associated with an increase in serious adverse events (30.0 vs. 32.8%), grade 5 adverse events (9.8 vs. 12.0%), or adverse events leading to permanent discontinuation (16.1 vs. 17.9%) compared with placebo/pemetrexed. A higher incidence of grade three or more elevated ALT (23 vs. 7%) and elevated AST (12 vs. 2%) – which are types of enzymes measured to determine liver health – as well as grade ≥3 diarrhoea (3.5 vs. 1%) were observed in patients treated with nintedanib* and pemetrexed. Grade three or more hypertension, bleeding, thrombosis, mucositis and neuropathy were comparable between the two treatment arms.2
“This study is part of the comprehensive LUME-Lung clinical trial program that is exploring the potential of nintedanib* in various lung cancer treatment settings. Boehringer Ingelheim is looking forward to sharing the data from the LUME-Lung 1 Phase III trial including overall survival data, which has been accepted as a late-breaker and will be presented on June 3rd at ASCO,” said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “The Phase III trial results in NSCLC for both afatinib* and nintedanib* represent the latest advancements from Boehringer Ingelheim’s robust oncology pipeline and our commitment to researching and developing new therapies for patients with cancer that are to this day difficult to treat.”
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Notes to Editors
www.newshome.com/oncology/lung-cancer/asco-2013-new-phase-iii-data-16th-may.aspx
*Afatinib, nintedanib and volasertib are investigational compounds and are not yet approved. Their safety and efficacy have not yet been fully established.
*Afatinib is an investigational compound and is not yet approved. Its safety and efficacy have not yet been fully established.
