Data in patients with malignant melanoma, who have been previously treated with pembrolizumab as adjuvant therapy, show a reduction in pembrolizumab efficacy upon rechallenge. We examined this scenario in patients with non-metastatic renal cell carcinoma (RCC) eligible for adjuvant pembrolizumab after nephrectomy. We hypothesized that a proportion of such patients will either require re-treatment with pembrolizumab upon metastatic progression prior to cancer-specific mortality (CSM) or die from other cause mortality (OCM).
We identified within the SEER database 10,635 patients, between 2004 and 2017, with a diagnosis of non-metastatic intermediate-high and high risk RCC, who had undergone nephrectomy and fulfilled criteria for enrollment in KEYNOTE-564. Kaplan-Meier analyses addressed overall survival (OS), CSM and OCM.
9,825 (92.4%) of the 10,635 patients had intermediate-high risk RCC and 9,456 (88.9%) underwent radical nephrectomy. Additionally, 760 (7.1%) harbored sarcomatoid features. In Kaplan-Meier analyses, median OS was 9.8 (9.1-11.4) years. At 10-years of follow-up, CSM rate was 36% and OCM rate was 22%.
Based on CSM, our observations indicate that by 10-years of follow-up 36% of patients treated with adjuvant pembrolizumab will require a rechallenge, in a setting where a checkpoint inhibitor may have reduced efficacy. Moreover, at 10-years of follow-up, 22% of patients with RCC, previously treated with adjuvant pembrolizumab, will die of other causes. These percentages should be strongly considered prior to routine use of adjuvant pembrolizumab, especially given an OS benefit has not been proven.
Seminars in oncology. 2022 Apr 29 [Epub ahead of print]
Rocco S Flammia, Benedikt Hoeh, Lukas Hohenhorst, Gabriele Sorce, Francesco Chierigo, Andrea Panunzio, Zhe Tian, Fred Saad, Costantino Leonardo, Alberto Briganti, Alessandro Antonelli, Carlo Terrone, Shahrokh F Shariat, Markus Graefen, Felix K H Chun, Francesco Montorsi, Michele Gallucci, Pierre I Karakiewicz
Department of Maternal-Child and Urological Sciences, Sapienza Rome University, Policlinico Umberto I Hospital, Rome, Italy; Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada. Electronic address: ., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology University of Verona, Verona, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada., Department of Maternal-Child and Urological Sciences, Sapienza Rome University, Policlinico Umberto I Hospital, Rome, Italy., Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Urology University of Verona, Verona, Italy., Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern, Dallas, TX; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; Department of Urology, Weill Cornell Medical College, New York, NY., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.