Aims: To evaluate the safety and maximum tolerated dose (MTD) of afatinib combined with nintedanib.
Materials & methods: Patients received afatinib 10-20 mg daily plus nintedanib 150-200 mg twice daily (28-day cycle). Dose escalation followed a 3+3 design.
Results: Patients received afatinib/nintedanib: 10/150 mg (n = 11); 10/200 mg (n = 13; MTD); 20/200 mg (n = 4). Four patients had dose-limiting toxicities (all grade 3): increased alanine aminotransferase (afatinib/nintedanib: 10/150 mg), diarrhea (10/200 mg), dehydration (20/200 mg), diarrhea with elevated liver enzymes (20/200 mg). Frequent treatment-related adverse events were diarrhea, nausea, anorexia, fatigue and vomiting. In total, 14 patients (46.2%) had objective responses at the MTD.
Conclusion: The MTD, afatinib 10 mg daily plus nintedanib 200 mg twice daily, had a manageable safety profile, but was considered subtherapeutic for Phase II evaluation.
Keywords: BIBF 1120; BIBW 2992; ErbB family blocker; Phase I; afatinib; nintedanib; pharmacokinetics; triple angiokinase inhibitor.