Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma |
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| Affiliation: | 1. Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Harvard Medical School, Boston, United States;2. Gustave Roussy Cancer Campus, University of Paris Sud, Department of Cancer Medicine, Villejuif, France;3. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States;4. Tom Baker Cancer Center and University of Calgary, Calgary, Canada;5. Kidney Cancer Program, Dana-Farber Harvard Cancer Center, Boston, United States;1. Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai, China;2. Department of Urinary Surgery of Lihuili Hospital, Ningbo, China;3. Department of Urinary Surgery of Changhai Hospital, Second Military Medical University, Shanghai, China;4. Urology Research Center of the Chinese People׳s Liberation Army, Changzheng Hospital, Second Military Medical University, Shanghai, China;1. Division of Urology, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA;2. Department of Urology, Massachusetts General Hospital, Boston, MA;3. Kidney Cancer Center, Dana-Farber Cancer Institute, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA;4. Section of Urologic Oncology, Rutgers Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ;5. Department of Urology, Stanford School of Medicine, Palo Alto, CA;6. Department of Urology, Marmara University School of Medicine, Istanbul, Turkey;1. Dana-Farber Cancer Institute, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA;2. Hospital del Mar, Barcelona, Spain;3. St Bartholomew''s Hospital, London, UK;4. IRCCS San Matteo University Hospital Fundantion, Pavia, Italy;5. Istituto Toscano Tumori, Arezzo, Italy;6. San Camilo and Forlanini Hospitals, Rome, Italy;7. GU Center of Excellence Texas Oncology, Dallas, TX;1. Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada;2. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;3. Vancouver Cancer Center, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;4. Cross Cancer Institute, Edmonton, Alberta, Canada;5. Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada;6. Karmanos Cancer Institute, Wayne State University, Detroit, MI;7. Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada;8. Princess Margaret Hospital, Toronto, Ontario, Canada;9. National Cancer Center, Singapore;10. London Regional Cancer Program, London, Ontario, Canada;11. Aarhus University, Aarhus, Denmark;12. Cleveland Clinic Taussig Cancer Center, Cleveland, OH;1. Princess Margaret Hospital, Toronto, Ontario, Canada;2. Asan Medical Centre, Seoul, South Korea;3. Stanford Cancer Centre, Stanford, CA;4. Sunnybrook Odette Cancer Institute, Toronto, Ontario, Canada;5. London Health Sciences Center, London, Ontario, Canada;6. Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada;7. Wayne State University, Detroit, MI;8. National Cancer Center, Institute of Bioengineering and Nanotechnology, Singapore;9. Yonsei University Hospital, Seoul, South Korea;10. Aarhus University Hospital, Aarhus, Denmark;11. Huntsman Cancer Institute, Salt Lake City, UT;12. BC Cancer Agency, Vancouver, British Columbia, Canada;13. Cross Cancer Institute, Edmonton, Alberta, Canada;14. Cleveland Clinic Taussig Cancer Institute, Cleveland, OH;15. Dana-Farber Cancer Institute, Harvard University, Boston, MA;16. Tom Baker Cancer Centre, Calgary, Alberta, Canada;1. Department of Oncology, Thomayer Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic;2. Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic;3. Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic;4. Department of Oncology, Motol University Hospital and Charles University Second Faculty of Medicine, Prague, Czech Republic;5. Department of Oncology, General University Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic;6. Department of Oncology, University Hospital, Pilsen, Czech Republic;7. Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic |
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| Abstract: | BackgroundMonoclonal antibodies that target the programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) pathway have shown antitumour activity in metastatic renal cell carcinoma (mRCC) and are currently being developed in first-line (in combination) and in previously treated patients. The efficacy targeted therapy (TT) after PD-1/PD-L1 blockade is still unknown.MethodsMedical records of mRCC patients treated with investigational PD-1 or PD-L1 inhibitors at 4 academic institutions were reviewed. Patients who received subsequent treatment with TT were selected to collect outcome measures of subsequent TT.ResultsOf 99 patients who received PD-1/PD-L1 blockade as part of clinical trials, 56 patients have received subsequent therapy: 44 patients received vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors and 12 received mammalian target of rapamycin (mTOR) inhibitors as first subsequent TT. Median follow up, from the start of subsequent TT was 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 blockade was administered as second-line, third-line or beyond third-line in 9 (16%), 24 (43%) and 23 patients (41%) respectively. Median time to treatment failure on subsequent TT was 6.6 months (range: 0.2+, 23.0). 1-year and 2 year overall survival from the initiation of subsequent TT was 58% (95% confidence interval (CI): 41–72%) and 36% (95% CI: 18–54%), respectively.ConclusionBoth VEGF/VEGFR and mTOR inhibitors demonstrate antitumour activity following PD-1/PD-L1 blockade. |
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| Keywords: | Renal cell carcinoma Targeted therapy PD-1 PD-L1 VEGFR mTOR |
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