A Phase I dose-escalation study of afatinib combined with nintedanib in patients with advanced solid tumors

作者：Gordon Michael S^*; Springett Gregory M; Su Yungpo Bernard; Ould Kaci Mahmoud; Wind Sven; Zhao Yihua; LoRusso Patricia M

来源：Future Oncology, 2015, 11(10): 1479-1491.

DOI：10.2217/fon.15.50

• afatinib
• BIBF 1120
• BIBW 2992
• ErbB family blocker
• nintedanib
• pharmacokinetics
• Phase I
• triple angiokinase inhibitor

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.

• 出版日期2015