Pancreatic cancer (PC) remains a disease difficult to treat. Afatinib, a novel, oral irreversible ErbB family blocker has shown efficacy in non-small-cell lung cancer bearing driver mutations of the epidermal growth factor receptor. This open-label, multicenter, randomised phase II trial evaluated the efficacy and safety for gemcitabine/afatinib vs. gemcitabine in metastatic PC.
Patients with histologically proven metastatic PC were randomised in a 2:1 ratio to receive either gemcitabine (1000mg/m2 i.v. weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40mg orally once daily) vs. gemcitabine alone as first-line treatment for metastatic disease. Overall survival (OS) was the primary endpoint.
Between April 2013 and January 2017, 119 patients from 25 German centers were randomised (79 patients for gemcitabine/afatinib and 40 for gemcitabine), of which 115 received at least one dose of study medication and 108 were eligible for the primary analysis. Median OS was 7.3 months for gemcitabine/afatinib vs. 7.4 months for gemcitabine, HR 1.06 (95% CI 0.68-1.65), p = 0.80. Median progression free survival (PFS) was 3.9 months for gemcitabine/afatinib vs. 3.8 months for gemcitabine, HR 0.87 (95% CI 0.56-1.34), p = 0.52. The objective overall response rate (ORR) was 9.9% for gemcitabine/afatinib vs. 10.8% for gemcitabine, respectively (p > 0.99). The rate of serious adverse events (SAEs) per patient was slightly higher for gemcitabine/afatinib vs. gemcitabine (1.66 vs. 1.53). The rate of adverse events was higher for gemcitabine/afatinib vs. gemcitabine, e.g. for main adverse events known for afatinib like diarrhoea (71% vs. 13%), epistaxis (33% vs. 0%) and skin rash (70% vs. 5%). However, the share of grade ≥3 in these events was low (16% for diarrhoea, 0% for epistaxis, 5% for skin rash; no grades 4 or 5).
The addition of afatinib to gemcitabine did not improve treatment efficacy. The combination had an acceptable safety profile with the main side effects for afatinib ranging within the known scope.
Clinical trial identification
EudraCT: 2011-004063-77; NCT01728818.
Legal entity responsible for the study
M. Haas: Research funding and travel grant: Boehringer Ingelheim. D. Waldschmidt: Consulting or advisory role: Bayer, Health Pharma BMS, Celgene Novartis, Roche, Pharma AG, Shire Baxalta, Sirtex; Honoraria: Bayer, Health Pharma BMS, Celgene, Novartis, Shire Baxalta, Sirtex; Research funding: Roche, Pharma AG, Shire Baxalta. A. Reinacher-Schick: Honoria: Amgen, Roche, Pfizer, Sanofi-Aventis, Merck, Shire, Celgene, Lilly, BMS, Advisory board member: Amgen, Roche, Pfizer, Sanofi-Aventis, Merck, Celgene, Lilly, BMS Studies sponsored by: Roche, Sanofi-Aventis, Celgene, Ipsen. T. Seufferlein: Research support: Celgene Shire Sanofi-Genzyme; Advisory board membership: Roche Celgene, Bayer, Shire. C.B. Westphalen: Consulting or advisory role: Celgene, Roche, Pharma, AG Shire, RedHill; Honoraria: IPSEN; Research funding: Roche Pharma AG. V. Heinemann: Honoraria: Amgen, Baxalta, Celgene, Merck, Roche, Sanofi, Sirtex, Medical; Consulting or advisory role: Amgen, Baxalta, Boehringer, Ingelheim, Celgene, Merck, Roche, Sanofi, Sirtex Medical; Research funding (institution): Amgen, Bayer, Boehringer Ingelheim, Celgene, IntegraGen, Merck, Roche, Sanofi, Sirtex Medical, Taiho Pharmaceutical; Travel accommodations expenses: Amgen Baxalta, Merck, Roche, Sirtex Medical. All other authors have declared no conflicts of interest.