Document Type
Article
Publication Date
5-7-2021
Abstract
Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue. The anti-angiogenic properties of pazopanib could overcome crizotinib drug resistance. Additionally, the anti-angiogenic properties of crizotinib could augment the clinical efficacy of pazopanib.
Methods: We evaluated the safety and responses in patients with advanced solid tumors treated with crizotinib and pazopanib.
Results: Eighty-two patients (median age 53 years, range 18-78 years) were enrolled. The median number of prior systemic therapies was 3 (range, 0-8). We were able to dose escalate to dose level 8 (crizotinib 250 mg twice daily and pazopanib 800 mg daily) with no MTD identified. Grade 3 or 4 toxicities were seen in 32% of patients with the highest prevalence being fatigue (n=9, 11%), diarrhea (n=6, 7%), vomiting (n=3, 4%), anemia (n=2, 2%) and ALT increased (n=2, 2%). Of the 82 patients, 61 (74%) had measurable disease by RECISTv1.1 and reached first restaging (6 weeks). Partial response (PR) was observed in 6/61 (10%) patients, and stable disease (SD) lasting ≥6 months was observed in 10/61 patients (16%) (total = 16/61 (26%) of patients with SD ≥6 months/PR).
Conclusion: Dose level 6 (crizotinib 200 mg twice daily and pazopanib 600 mg daily) was the most tolerable dosing of the combination and can be used in future studies. We also observed moderate clinical activity in patients with advanced solid tumors that had received numerous prior therapies.
Recommended Citation
Piha-Paul, Sarina A; Dumbrava, Ecaterina E; Nair, Binoj C; Xiong, Wendy; Xu, Li; Mostorino, Rosa; Subbiah, Vivek; Tannir, Nizar; Fu, Siqing; Naing, Aung; Janku, Filip; Karp, Daniel D; Patel, Shreyaskumar; Daw, Najat C; Hong, David; Meric-Bernstam, Funda; and Zinner, Ralph G., "A Phase I Trial of the MET/ALK/ROS1 Inhibitor Crizotinib Combined with the VEGF Inhibitor Pazopanib in Patients with Advanced Solid Malignancies" (2021). Department of Medical Oncology Faculty Papers. Paper 141.
https://jdc.jefferson.edu/medoncfp/141
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
PubMed ID
33994796
Language
English
Comments
This article is the author's final published version in OncoTargets and Therapy, Volume 14, pp. 3037-3049.
OncoTargets and Therapy, published by Dove Medical Press, is acknowledged as the article's original place of publication.
The published version is available at https://doi.org/10.2147/OTT.S291801
Copyright © 2021 Piha-Paul et al.
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