JU INSIGHT Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response

By: Kosuke Takemura, MD, PhD, MPH, Tom Baker Cancer Centre, University of Calgary, Alberta, Canada; Vishal Navani, MD, Tom Baker Cancer Centre, University of Calgary, Alberta, Canada; Matthew S. Ernst, MD, Tom Baker Cancer Centre, University of Calgary, Alberta, Canada; J. Connor Wells, MD, BC Cancer Agency, Vancouver, British Columbia, Canada; Luis Meza, MD, City of Hope Comprehensive Cancer Center, Duarte, California; Sumanta K. Pal, MD, City of Hope Comprehensive Cancer Center, Duarte, California; Jae-Lyun Lee, MD, PhD, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Haoran Li, MD, PhD, Huntsman Cancer Institute, University of Utah, Salt Lake City; Neeraj Agarwal, MD, Huntsman Cancer Institute, University of Utah, Salt Lake City; Ajjai S. Alva, MD, University of Michigan Rogel Cancer Center, Ann Arbor; Aaron R. Hansen, BSc, MBBS, FRACP, Princess Margaret Cancer Centre, University of Toronto, Ontario, Canada; Naveen S. Basappa, MD, Cross Cancer Institute, University of Alberta, Edmonton, Canada; Bernadett Szabados, MD, Barts Cancer Institute, Queen Mary University of London, United Kingdom; Thomas Powles, MBBS, MRCP, MD, Barts Cancer Institute, Queen Mary University of London, United Kingdom; Ben Tran, MBBS, FRACP, Peter MacCallum Cancer Centre, Melbourne, Australia; Christopher M. Hocking, MBBS, FRACP, Lyell McEwin Hospital, Adelaide, Australia; Benoit Beuselinck, MD, PhD, Leuven Cancer Institute, KU Leuven, Belgium; Takeshi Yuasa, MD, PhD, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Toni K. Choueiri, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Daniel Y. C. Heng, MD, MPH, FRCPC, Tom Baker Cancer Centre, University of Calgary, Alberta, Canada | Posted on: 20 Apr 2023

Takemura K, Navani V, Ernst MS, et al. Characterization of patients with metastatic renal cell carcinoma experiencing complete response to first-line therapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium. J Urol. 2023;209(4):701-709.

Study Need and Importance

Traditionally, complete response (CR) was an uncommon event in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitor (TKI). Several clinical trials demonstrated that contemporary immuno-oncology (IO)–based combination therapy had a higher CR rate than TKI monotherapy. However, there has been limited real-world evidence on the baseline characteristics and outcomes of patients who experience CR to first-line therapies.

What We Found

In this study, we used the IMDC (International mRCC Database Consortium) and identified 52 (4.6%) of 1,126 and 223 (3.0%) of 7,557 patients who experienced CR to IO-based and TKI therapies, respectively. Favorable- or intermediate-IMDC risk and absence of bone metastasis were associated with CR regardless of first-line therapies. Among patients who experienced CR, adverse clinicopathological features such as non–clear cell histology, sarcomatoid dedifferentiation, and multiple sites of metastases were more frequently observed in the IO-based cohort than in the TKI cohort. Median overall survival time for the IO-based cohort with CR and non-CR was not reached and 44.4 months, respectively, whereas median overall survival time for the TKI cohort with CR and non-CR was 125.5 months and 26.5 months, respectively (see Figure). CR was an independent favorable prognostic factor after adjustment for other covariates.

Figure. Kaplan-Meier curves for overall survival by the type of first-line therapies received and best overall response. CR indicates complete response; IO, immuno-oncology; TKI, tyrosine kinase inhibitor.

Limitations

Although the sample size is among the largest reported to date, this study is limited by its retrospective design, clinician assessment of best overall response rather than blinded independent central review, and a selected patient population from high-income countries.

Interpretation for Patient Care

This study characterized patients with mRCC who did or did not experience CR to first-line therapies. These results suggest that CR rates may not be as high in the real-world population as in the clinical trial population and that contemporary IO-based combination therapy may have a potential to overcome aggressive phenotypes of mRCC.