Related Experiment Video
Updated: Apr 12, 2026
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
A Phase I dose-escalation study of afatinib combined with nintedanib in patients with advanced solid tumors
Michael S Gordon1, Gregory M Springett, Yungpo Bernard Su
1Pinnacle Oncology Hematology, 9055 E Del Camino, Suite 100, Scottsdale, AZ 85258, USA.
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.
