Tumor growth rate to assess therapy response to immune-based combinations for metastatic renal cell carcinoma

ABSTRACT

Background

Radiological response assessment is becoming challenging with novel immune-based combinations for metastatic renal cell carcinoma (mRCC). RECIST criteria appear not exhaustively adequate to capture the kinetics of treatment response, which is better reflected by tumor growth rate (TGR). We explored TGR changes during first-line treatments and its association with clinical outcomes in mRCC.

Research design and methods

We retrospectively evaluated TGR in untreated patients undergoing pembrolizumab/axitinib (P/A) or tyrosine-kinase inhibitors (TKI). TGR was calculated at the first (TGR1, after 3 months) and the second (TGR2, after 6 months) evaluation, thus assessing the TGR2-TGR1 difference.

Results

Thirty-three patients were included (P/A n = 15, TKIs n = 18). Volumes firstly decreased more rapidly with TKIs, and then more slowly. Volumes initially remained stable with P/A, quickly decreasing until the second evaluation. TGR1 was related to progression-free survival (PFS; p = 0.023) and overall survival (p = 0.046) with P/A. TGR2 was correlated with PFS in all patients (p = 0.025). Patients with higher velocity volume reduction appeared to have improved survival benefits than patients with lower velocity considering both treatments, but especially with P/A.

Conclusion

Combining immunotherapy with TKIs has an important role in enhancing the rapidity of tumor shrinkage. A rapid disease volume reduction correlates with better OS and PFS.

KEYWORDS:

• Immune checkpoint inhibitor
• immune-based combinations
• metastatic renal cell carcinoma
• radiological assessment
• tyrosine kinase-inhibitor
• tumor growth rate

Reviewer disclosures

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

Ethical approval

This study was approved by local IRB (Comitato Etico Indipendente, IRCCS Azienda Ospedaliero-Universitaria di Bologna, protocol code: PRIORI, 321/2019/Sper/AOUBo) and was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author contributions

Francesco Massari and Veronica Mollica contributed to the study conception and design. Material preparation, data collection and analysis were performed by Veronica Mollica, Matteo Rosellini, Stefano Brocchi and Andrea Marchetti. The first draft of the manuscript was written by Veronica Mollica, Matteo Rosellini, Francesco Massari and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Declaration of interest

F Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work; M Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas and Bayer, all unrelated to the present paper. The work reported in this publication was supported by the Italian Ministry of Health, RC-2022- 2773458. The other Authors have no relevant financial or non-financial interests to disclose.

Additional information

Funding

This paper was not funded.