OS data from LUX-Lung 7 head-to-head trial of Gilotrif® (afatinib) versus Iressa® (gefitinib) presented at ESMO

October 9, 2016 – RIDGEFIELD. Boehringer Ingelheim announced results from the LUX-Lung 7 trial that directly compared the efficacy and safety of second-generation EGFR-directed therapy Gilotrif® (afatinib) and first-generation Iressa® (gefitinib), in the first-line treatment of patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). The trial investigated overall survival (OS) as a primary endpoint and a reduction in the risk of death (14%) was observed for patients treated with afatinib versus gefitinib. The median survival of patients treated with afatinib was 27.9 months compared to 24.5 months for those receiving gefitinib, without reaching significance. The OS outcomes observed with afatinib were consistent across common EGFR mutation types.

Details of the analysis will be presented today at the European Society of Medical Oncology (ESMO) 2016 Congress in Copenhagen, Denmark, October 7 – 11 (abstract #LBA43 - Oral presentation, NSCLC, metastatic 1, Sunday, October 9, 11:45 - 12:00 CEST (5:45 – 6:00 ET)).

“The LUX-Lung 7 trial provides new insight into first-line treatment options for EGFR mutation-positive NSCLC patients and is the first global head-to-head trial directly comparing two EGFR-directed therapies,” commented Shirish Gadgeel, M.D., leader of the Thoracic Oncology Multidisciplinary, Karmanos Cancer Center, Detroit. “These study findings may help inform treatment decisions for patients whose tumors have EGFR mutations.”

Updated results also confirmed the primary analysis that showed the global Phase IIb LUX-Lung 7 trial met two of its three co-primary endpoints of progression-free survival (PFS) by independent review and time to treatment failure (a measure of time between start and discontinuation of treatment for any reason). Results from the primary analysis, presented in 2015, showed that afatinib significantly reduced the risk of lung cancer progression and the risk of treatment failure, both by 27% versus gefitinib. The improvement in PFS became more pronounced over time. After two years of treatment, more than twice as many patients on afatinib were alive and progression-free than those on gefitinib (after 18 months; 27% vs 15% and after 24 months; 18% vs 8%). Additionally, significantly more patients experienced an objective response (ORR; a clinically meaningful decrease in tumor size) with afatinib when compared to gefitinib.

Both afatinib and gefitinib demonstrated similar improvements in patient-reported outcome measures in the LUX-Lung 7 trial with no significant differences in health-related quality of life with afatinib compared to gefitinib treatment. Treatment with both afatinib and gefitinib was generally tolerable, leading to an equal rate of treatment-related discontinuation in both arms (6%). Adverse events (AEs) observed in the trial were consistent with the known safety profiles of both treatments.  The overall frequency of serious AEs was 44.4% for afatinib and 37.1% for gefitinib. The most common grade ≥3 related AEs with afatinib were: diarrhea (13%) and rash/acne (9%), and with gefitinib: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increase (9%) and rash/acne (3%). Drug-related interstitial lung disease was reported for four patients on gefitinib and no patients on afatinib. Dose modification of afatinib was available in patients who met a set criteria in order to better manage AEs. As gefitinib is only available in one dose formulation, no dose reduction was administered.  

“We believe that the latest results of the LUX-Lung 7 trial data adds to the growing body of evidence that reinforces the treatment benefits of afatanib in patients with these types of tumors,” said Martina Flammer, M.D., Vice President, Clinical Development & Medical Affairs Specialty Care, Boehringer Ingelheim.

Afatinib is approved in over 70 countries for the first-line treatment of EGFR mutation-positive NSCLC. Approval of afatinib in this indication was based on the primary endpoint of PFS from the LUX-Lung 3 clinical trial where afatinib significantly delayed tumor growth when compared to standard chemotherapy. In addition, afatinib is the first treatment to have shown an OS benefit for patients with specific types of EGFR mutation-positive NSCLC compared to chemotherapy. A significant OS benefit was demonstrated independently in the LUX-Lung 3 and 6 trials for patients with the most common EGFR mutation (del19) compared to chemotherapy. Afatinib is also approved in the U.S., EU and other markets for the treatment of patients with advanced squamous cell carcinoma (SqCC) of the lung whose disease has progressed on or after treatment with platinum-based chemotherapy. Approval of afatinib in this indication is based on results of the LUX-Lung 8 study, which showed a significantly improved overall survival and progression-free survival compared to Tarceva® (erlotinib) in patients with SqCC of the lung.

About the LUX-Lung 7 trialLUX-Lung 7 is the first global, head-to-head trial comparing second- and first-generation EGFR-directed therapies (afatinib and gefitinib respectively) for patients with EGFR mutation-positive NSCLC who received no prior treatment. The Phase IIb trial included 319 patients with advanced stage NSCLC harboring common EGFR mutations (del19 or L858R). The trial’s co-primary endpoints were PFS by independent review, time to treatment failure and OS; and the secondary endpoints included ORR, disease control rate, tumor shrinkage, patient-reported outcomes and safety.

Results from the primary analysis: compared to gefitinib, afatinib significantly improved:

Data from the trial showed a reduction in the risk of death for patients treated with afatinib compared to gefitinib, without reaching significance (HR=0.86; 95% CI, 0.66‒1.12; p=0.2580; median: 27.9 months [afatinib] versus 24.5 months [gefitinib]). These OS data have a maturity of 71%, with further analysis to follow once full maturity has been reached.

SOURCE Boehringer Ingelheim