Tailoring treatment with cabozantinib or pazopanib in patients with metastatic renal cell carcinoma: does it affect outcome?

ABSTRACT

Background

Metastatic renal cell carcinoma (mRCC) treatment is still largely based on TKI use. Treatment adjustment due to toxicities is often needed. The aim of the present study was to determine the impact of treatment modifications on the outcome of mRCC patients treated with cabozantinib or pazopanib.

Research design and methods

This retrospective multicenter study enrolled consecutive patients receiving cabozantinib or pazopanib between January 2012 and December 2020. We evaluated the correlation of TKI treatment modifications with grade 3–4 toxicities and progression-free (PFS) and overall survival (OS). We also performed a landmark analysis excluding patients who did not undergo at least 5 months of therapy.

Results

Among 301 patients, 179 (59%) were treated with pazopanib, 122 (41%) with cabozantinib. Treatment modifications were related to grade 3–4 toxicities (p < 0.0001). We observed a statistically significant longer PFS and OS in patients who underwent dose reductions (p < 0.0001 for both PFS and OS), temporary interruption (p < 0.0001 for both PFS and OS) and schedule modifications (p = 0.007 for PFS and p = 0.012 for OS) at univariate analysis. These results were confirmed at multivariable and landmark analyses.

Conclusions

Tailoring treatment with pazopanib and cabozantinib was associated with better PFS/OS.

KEYWORDS:

• Cabozantinib
• dose reduction
• metastatic renal cell carcinoma (mRCC)
• pazopanib
• prognostic
• schedule modification
• tailoring
• temporary interruption

Declaration of interest

S. Buti has received honoraria as a speaker at scientific events and has served in an advisory role for Bristol-Myers Squibb, Pfizer, MSD, Ipsen, AstraZeneca, and Novartis, and has received research funding from Novartis.

U. De Giorgi has received honoraria for advisory boards and speaker fees for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Roche, Novartis, Clovis, GSK, AstraZeneca and has received institutional research grants from; AstraZeneca, Sanofi, and Roche.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

MC: conceptualization, project administration, visualization, writing – original draft, writing: review & editing. DG: formal analysis, methodology, validation, writing: review & editing. GS, UDG, NB, GF, GCG, SER, SP, OC, AS, SK, AM, CC, MS, EV, AR, MS, AM, GR, MB: data curation, writing: review & editing. GLB: writing: critical review and editing. SB: conceptualization, data curation, formal analysis, methodology, project administration, visualization, writing – original draft, writing: review & editing, supervision. All the authors approved the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2023.2200168

Additional information

Funding

This paper received no funding.