BACKGROUND AND OBJECTIVE: 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. METHODS: 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. KEY FINDINGS AND LIMITATIONS: 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. CONCLUSIONS AND CLINICAL IMPLICATIONS: 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. PATIENT SUMMARY: 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.

Beatson West of Scotland Cancer Centre Glasgow UK; University of Glasgow Glasgow UK

Center of Molecular and Cellular Oncology Yale Cancer Center Yale School of Medicine New Haven CT USA

Department of Data Sciences Dana Farber Cancer Institute Boston MA USA

Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston TX USA

Department of Internal Medicine Division of Hematology Oncology UT Southwestern Medical Center Dallas TX USA

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 and Experimental Therapeutics City of Hope Comprehensive Cancer Center Duarte CA USA

Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA

Department of Medical Oncology Fiona Stanley Hospital Perth Western Australia Australia

Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Milan Italy

Department of Medical Oncology UC San Diego La Jolla CA USA

Department of Medical Oncology University Hospital of Bordeaux Bordeaux France

Department of Medicine and Surgery University of Parma Parma Italy; Medical Oncology Unit University Hospital of Parma Parma Italy

Department of Medicine Vanderbilt University Medical Center Nashville TN USA

Department of Oncology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Urology The University of Texas MD Anderson Cancer Center Houston TX USA

Division of Hematology and Oncology Department of Internal Medicine University of Michigan Ann Arbor MI USA

Hospital 1ro de Octubre Mexico City Mexico

Hospital Sirio Libanés Buenos Aires Argentina

Hospital Universitario 12 de Octubre Madrid Spain

IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Macquarie University Sydney Australia

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna 40138 Italy; Department of Medical and Surgical Sciences University of Bologna Bologna 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

Tom Baker Cancer Centre University of Calgary Calgary Canada

Winship Cancer Institute of Emory University Atlanta GA USA

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Real-world evidences on adjuvant Pembrolizumab for renal cell carcinoma: results from the multicenter real-world ARON-1 study