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First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study
T. El Zarif, K. Semaan, W. Xie, M. Eid, M. Zarba, W. Issa, T. Zhang, CB. Nguyen, A. Alva, CC. Fahey, KE. Beckermann, JA. Karam, MT. Campbell, G. Procopio, M. Stellato, S. Buti, A. Zemankova, B. Melichar, F. Massari, V. Mollica, B. Venugopal, H....
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články, multicentrická studie
- MeSH
- adjuvantní chemoterapie MeSH
- doba přežití bez progrese choroby MeSH
- humanizované monoklonální protilátky terapeutické užití škodlivé účinky MeSH
- imunoterapie metody MeSH
- karcinom z renálních buněk * farmakoterapie sekundární mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory ledvin * farmakoterapie patologie mortalita MeSH
- protinádorové látky imunologicky aktivní terapeutické užití škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
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
Department of Data Sciences Dana Farber Cancer Institute Boston MA USA
Department of Internal Medicine Yale School of Medicine New Haven CT USA
Department of Medical and Surgical Sciences University of Bologna Bologna Italy
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
Department of Medicine Vanderbilt University Medical Center Nashville TN USA
Department of Urology The University of Texas MD Anderson Cancer Center Houston TX 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
Medical Oncology Unit University Hospital of Parma Parma Italy
The Verspeeten Family Cancer Centre at London Health Sciences Centre London Ontario Canada
Tom Baker Cancer Centre University of Calgary Calgary Canada
Citace poskytuje Crossref.org
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