Global Named Patient Use Program of Afatinib in Advanced Non-Small-Cell Lung Carcinoma Patients Who Progressed Following Prior Therapies

Abstract

Aim:A global afatinib named patient use program in non-small-cell lung carcinoma (NSCLC) commenced in 2010. Materials & methods: Eligible NSCLC patients had progressed after clinical benefit on prior erlotinib/gefitinib and/or had activating EGFR/HER2 mutations, exhausted all other treatments, and were ineligible for afatinib trials. Results: Data, as of January 2016, were reported on 3966 heavily pretreated NSCLC patients (41 countries; 6 continents). Among 2595/3966 (65.4%) patients with tumor EGFR status, 2407 (92.8%) were EGFR mutation positive. Median time to treatment failure (2862/3966 [72.2%] patients with available data) was 4.4 months. Among 1141/2862 (39.9%) patients with response reported, objective response rate was 23.4% (267/1141). Safety findings were as expected. Conclusion: Time to treatment failure durations and objective response rates were encouraging. Afatinib is an orally available, irreversible ErbB family (EGFR/ErbB1; HER2/ErbB2; and HER4/ErbB4) blocker approved in the European Union, USA, Canada, Switzerland and several Asian, Latin American and Middle East countries for non-small-cell lung carcinoma (NSCLC) patients with certain sensitizing EGFR mutations [1,2]. In contrast to the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib, afatinib covalently binds to the ErbB receptor in vitro, irreversibly blocking signaling with sustained inhibition of mitogenic activity [3]. The global, Phase III LUX-Lung 3 (LL3) trial in metastatic EGFR mutation-positive NSCLC demonstrated a significant improvement in the primary end point of progression-free survival (PFS) with first-line afatinib 40 mg/day versus pemetrexed/cisplatin (11.1 vs 6.9 months; hazard ratio [HR]: 0.58; p = 0.001) for all patients with EGFR mutations [4]. A larger median PFS difference was noted for patients with common mutations of Del19 and Future Oncol. (Epub ahead of print)

Treatment outcome and clinical characteristics of HER2 mutated advanced non‐small cell lung cancer patients in China

“…Among small molecule TKIs, afatinib was most widely used in China in recent years, with PFS ranging from 2.9 to 6 months. 20,[24][25][26][27] Poziotinib, neratinib and pyrotinib had similar PFS, with 4.5-5.5 months, 5.5 and 6.4 months, respectively. 9,28,29 Dacomitinib and Osimertinib had weaker effects on this population, either with a short PFS or being invalid in cell line experiments.…”

“…This could mean that trastuzumab or T‐DM1 might be beneficial to a minority of patients. Among small molecule TKIs, afatinib was most widely used in China in recent years, with PFS ranging from 2.9 to 6 months . Poziotinib, neratinib and pyrotinib had similar PFS, with 4.5–5.5 months, 5.5 and 6.4 months, respectively .…”

Activity of Afatinib in Heavily Pretreated Patients With ERBB2 Mutation–Positive Advanced NSCLC: Findings From a Global Named Patient Use Program

“…Of 5650 patients with NSCLC from 49 countries enrolled in the NPU program, 3966 patients from 41 countries were included in the overall analysis. 22 A total of 28 patients were documented as having ERBB2 mutation-positive NSCLC (16 patients with ERBB2 mutations were identified in the original analysis of the overall NPU program population 22 ; an additional 12 patients have since been identified and were included in the present analysis). These patients were enrolled in Europe (8 in Switzerland, 2 in Spain, 1 each in Belgium, Germany, The Netherlands, and Slovenia), Taiwan (11 patients), Israel (2 patients), and Argentina (1 patient).…”

“…Between May 2010 and January 2016, more than 5600 patients with NSCLC received afatinib under the NPU program, and almost 4000 patients were eligible for inclusion in an analysis of the efficacy and safety of afatinib in this setting; among those for whom response data were available, 23.4% achieved an objective response. 22 Here, we report treatment outcomes for the subset of patients with ERBB2 mutation-positive NSCLC who were treated as part of the NPU program.…”

Ethics framework for treatment use of investigational drugs

“…In line with this, a case was reported recently when treatment with an ID of one patient was approved by the FDA based merely on data from preclinical studies; the treatment was performed at a leading medical center and the results were published by a top-tier medical journal [ 30 ]. However, large programs involving hundreds or thousands of patients have been begun mostly after the completion of Phase 3 trials [ 31 , 32 ].…”