Adjuvant pembrolizumab significantly improved overall survival (OS) in renal cell carcinoma (RCC), but real-world data on sequential treatment are scarce. We sought to evaluate the clinical outcomes of first-line (1L) systemic therapy following adjuvant immune oncology (IO)-based regimens.
A retrospective study including patients with recurrent RCC following adjuvant IO across 29 international institutions was conducted. The primary endpoint was progression-free survival (PFS) on 1L systemic therapy estimated using the Kaplan-Meier method. Preplanned subanalyses of clinical outcomes by type of 1L systemic therapy, recurrence timing, and International Metastatic RCC Database Consortium (IMDC) risk groups were performed. Treatment-related adverse events leading to treatment discontinuation, dose reduction, or corticosteroid use were assessed.
A total of 94 patients were included. Most received adjuvant pembrolizumab (n = 37, 39%), atezolizumab (n = 28, 30%), or nivolumab + ipilimumab (n = 15, 16%). The cohort included 49 (52%) patients who had recurrence within 3 mo of the last adjuvant IO dose, whereas 45 (48%) recurred beyond 3 mo. Bone metastases were significantly higher in tumors recurring at <3 mo (10/49, 20%) than those recurring at >3 mo (1/45, 2.2%; p = 0.008). Most patients received 1L vascular endothelial growth factor-targeted therapy (VEGF-TT; n = 37, 39%), IO + VEGF-TT (n = 26, 28%), or IO + IO (n = 12, 13%). The remaining underwent local therapy. The median follow-up for the 1L systemic therapy cohort was 15 mo. The 18-mo PFS and OS rates were 45% (95% confidence interval [CI]: 34-60) and 85% (95% CI: 75-95), respectively. Treatment-related adverse events occurred in 32 (42%) patients and included skin toxicity (n = 7, 9.2%), fatigue (n = 6, 7.9%), and diarrhea/colitis (n = 4, 5.3%). Limitations included selecting patients from large academic centers and the short follow-up period.
A subset of patients with recurrent RCC following adjuvant IO respond to systemic therapies, including VEGF-TT and IO-based regimens. Notably, patients with favorable-risk disease may derive more benefit from VEGF-TT than from IO therapies in this setting. Future approaches utilizing radiographic tools and biomarker-based liquid biopsies are warranted to detect occult metastatic disease and identify candidate patients for adjuvant IO therapy.
Adjuvant pembrolizumab significantly improved overall survival in renal cell carcinoma (RCC). There are limited data on clinical outcomes after the recurrence of RCC tumors following adjuvant immunotherapy. In this study, we find that patients respond to subsequent systemic therapies across different treatment options.
European urology. 2024 Aug 14 [Epub ahead of print]
Talal El Zarif, Karl Semaan, Wanling Xie, Marc Eid, Martin Zarba, Wadih Issa, Tian Zhang, Charles B Nguyen, Ajjai Alva, Catherine C Fahey, Kathryn E Beckermann, Jose A Karam, Matthew T Campbell, Giuseppe Procopio, Marco Stellato, Sebastiano Buti, Anezka Zemankova, Bohuslav Melichar, Francesco Massari, Veronica Mollica, Balaji Venugopal, Hedyeh Ebrahimi, Guillermo de Velasco, Howard Paul Gurney, Ugo De Giorgi, Omi Parikh, Eric Winquist, Viraj Master, Abraham Ruiz Garcia, Hernan Javier Cutuli, Thomas Robert Ferguson, Marine Gross-Goupil, Sylvan C Baca, Sumanta K Pal, David A Braun, Rana R McKay, Daniel Y C Heng, Toni K Choueiri
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA., Tom Baker Cancer Centre, University of Calgary, Calgary, Canada., Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas, TX, USA., Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Department of Medicine and Surgery, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy., Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Beatson West of Scotland Cancer Centre, Glasgow, UK; University of Glasgow, Glasgow, UK., Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Hospital Universitario 12 de Octubre, Madrid, Spain., Macquarie University, Sydney, Australia., IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Royal Preston Hospital-Lancashire Teaching Hospitals National Health Service Foundation Trust, Preston, UK., The Verspeeten Family Cancer Centre at London Health Sciences Centre, London, Ontario, Canada., Winship Cancer Institute of Emory University, Atlanta, GA, USA., Hospital 1ro de Octubre, Mexico City, Mexico., Hospital Sirio Libanés, Buenos Aires, Argentina., Department of Medical Oncology, Fiona Stanley Hospital, Perth, Western Australia, Australia., Department of Medical Oncology, University Hospital of Bordeaux, Bordeaux, France., Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA., Department of Medical Oncology, UC San Diego, La Jolla, CA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: .