Patients with mRCC who achieve a complete response (CR) to immuno-oncology (IO) combinations have an excellent prognosis and may experience prolonged responses. However, real-world data on CR durability, mortality, and need for subsequent therapy remain limited.
Using the International mRCC Database Consortium (IMDC), we identified patients with mRCC who achieved a documented CR to first-line treatment between 2015 and 2022. We described baseline characteristics, time to next treatment (TTNT), time to second line (TT2L), overall survival (OS), and use of subsequent therapies in patients treated with a vascular endotelial growth factor receptor pathway targeted therapy vascular endotelial growth factor (VEGF), IO plus VEGF (IO-VE), or Ipilimumab plus Nivolumab (IOIO).
CR was achieved with IO-VE in 25 of 610 (4.1%) patients, with IO-IO in 82 of 1313 (6.2%), and with VEGF in 46 of 2980 (1.5%) patients. OS in patients with CRs was not significantly different (log-rank P = .42) among the 3 treatment groups. After a median follow-up of 46.7 months, 4-year OS was for IO-VE 100% (95% CI, 100%-100%; HR ref), for IO-IO 92.9% (95% CI, 86.2%-100%; HR 1.89, 95% CI, 0.22-16.4), and for VEGF 94.8% (95% CI 88%-100%; HR 3.18, 95% CI 0.4-25.2). In the IO-VE cohort, 5 (20%) started second-line therapy, and 1 died; in IO-IO, 11 (13.4%) began second-line, and 5 (6.1%) died; and in VEGF, 17 (37%) started second-line, and 9 (19.6%) died. TTNT was not reached for any treatment, and TT2L was in IO-VE 46.8 months (95% CI, 27.5-NR), in IO-IO 30.2 months (95% CI, 21.5-NR), and in VEGF 23 months (95% CI, 14.3-51.7) (P = .66). IO rechallenge occurred in 20% (n = 1) of IO-VE and 63.6% (n = 7) of IO-IO patients receiving second-line, with CR to second-line in 2/8, PR in 4/8, standard deviation in 2/8, and no deaths.
This real-world study confirms that achieving CR confers an excellent prognosis. However, CR does not guarantee a cure, as a subset of patients do experience a relapse. Retreatment with IO was frequent and effective. These results support the significance of CR but highlight the need for ongoing surveillance and tailored care.
Clinical genitourinary cancer. 2026 Mar 15 [Epub ahead of print]
Martin Zarba, David Maj, Razane El Hajj Chehade, Karl Semaan, John Connor Wells, Frede Donskov, Rana R McKay, Juan Pablo Sade, Kosuke Takemura, Lori A Wood, Ian D Davis, Ulka Vaishampayan, Laura Basterretxea, Camillo Porta, Cristina Suarez, Guillermo de Velasco, Ali Moradi, Toni K Choueiri, Daniel Y C Heng
Arthur Child Comprehensive Cancer Centre, University of Calgary, Calgary, Canada. Electronic address: ., Arthur Child Comprehensive Cancer Centre, University of Calgary, Calgary, Canada., Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Department of Medical Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Medical Oncology, University of California San Diego, San Diego, CA., Department of Medical Oncology, Instituto Alexander Fleming, Buenos Aires, Argentina., Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Department of Medical Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, NS., Department of Medical Oncology, Monash University Eastern Health Clinical School, Melbourne, Australia., Department of Medical Oncology, University of Michigan Medical Center, Ann Arbor, MI., Department of Medical Oncology, Hospital Universitario Donostia, Donostia-San Sebastian, Spain., Department of Medical Oncology, Policlinico Consorziale, Bari, Italy., Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Guillermo de Velasco, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA.