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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

4233 - Clinical Outcomes of Patients with Metastatic Renal Cell Carcinoma (mRCC) Treated with Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitors (TKI) and Mammalian Target of Rapamycin Inhibitors (mTORI) after Immuno-oncology (IO) Checkpoint Inhibitors


22 Oct 2018


Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care


Tumour Site

Renal Cell Cancer


Jeffrey Graham


Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283


J. Graham1, J.C. Wells1, R. McKay2, U.N. Vaishampayan3, A. Hansen4, F. Donskov5, G.A. Bjarnason6, B. Beuselinck7, G. De Velasco8, M.S. Duh9, L. Huynh9, R. Chang9, G. Zanotti10, K. Ramaswamy10, T.K. Choueiri11, D.Y.C. Heng1

Author affiliations

  • 1 Medical Oncology, University of Calgary, T2N 4N2 - Calgary/CA
  • 2 Medical Oncology, University of California San Diego, San Diego/US
  • 3 Oncology, Karmanos Cancer Institute, 48201-2013 - Detroit/US
  • 4 Medical Oncology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 5 Department Of Oncology, Aarhus University Hospital, 8000 - Aarhus/DK
  • 6 Medical Oncology, Sunnybrook Odette Cancer Center, Sunnybrook HSC, M4N 3M5 - Toronto/CA
  • 7 General Medical Oncology, University Hospitals Leuven, 3000 - Leuven/BE
  • 8 Medical Oncology, University Hospital 12 de Octubre, Madrid/ES
  • 9 Health Economics And Outcomes Research, Analysis Group, Inc, 02199 - Boston/US
  • 10 Global Heor, Oncology, Pfizer, Inc., New York/US
  • 11 Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US


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Abstract 4233


In an era of increasing treatment options for mRCC, optimal treatment sequence after IO therapy has not been well established. This study compares the effect of targeted therapy (TT) (VEGFR TKI [axitinib, sunitinib, cabozantinib, pazopanib, bevacizumab, and sorafenib] vs mTORI [everolimus and temsirolimus]) after progression on IO therapy.


Data from 7 International mRCC Database Consortium (IMDC) centers were used to examine time to treatment discontinuation (TTD: time from TT initiation to discontinuation for any reason) and objective response rate (ORR: complete or partial tumor response) among mRCC patients (pts) treated with TT after IO between 2010-2018. Kaplan Meier analysis and Cox proportional hazards model adjusting for age, sex, IMDC risk score, and line of therapy were conducted. Overall survival will be reported when data is more mature.


Pts treated with VEGFR TKI (N = 156 [85%]) and mTORI (N = 28 [15%]) post IO had similar age and IMDC risk scores (mean age: 61 vs 63 years; IMDC favorable: 5% vs 8%; IMDC intermediate: 62% vs 48%). Most common TT post IO were axitinib (35%), cabozantinib (18%), and sunitinib (15%). Unadjusted median TTD was significantly longer for VEGFR TKI vs mTORI (5.3 vs 2.5 months, p = 0.002). VEGFR TKI vs mTORI post IO was significantly associated with a longer TTD (adjusted hazard ratio [aHR]: 0.44, p = 0.002). A trend toward better TTD with axitinib post IO vs other TT was observed (aHR: 0.66, p = 0.08). ORR was numerically higher in VEGFR TKI vs mTORI. Reported results are across all lines of therapy. The table has descriptive statistics.Table: 889P

Descriptive statistics of clinical outcomes among patients treated with targeted therapy (i.e., VEGFR TKI, mTORI) subsequent to IO treatment

Total NNumber of treatment discontinuation for any reason (%)Median TTD, (95% CI) monthsObjective response rate1 N (%)
All184118 (64)4.9 (4.0, 5.6)20 (17)
By class
All lines15693 (60)5.3 (4.3, 6.9)19 (20)
2nd line4428 (64)3.8 (3.2, 5.4)7 (23)
3rd line7243 (60)5.7 (4.3, 9.8)10 (22)
≥ 4th line4022 (55)6.1 (4.2, 10.9)2 (10)
All lines2825 (89)2.5 (1.4, 3.4)1 (5)
2nd line0---
3rd line2019 (95)2.3 (1.0, 4.9)1 (6)
≥ 4th line86 (75)3.2 (1.3, 4.9)0 (0)

IO: immuno-oncology; VEGFR TKI: vascular endothelial growth factor receptor tyrosine kinase inhibitor; mTORI: mammalian target of rapamycin inhibitor; CI: confidence interval; ORR: objective response rate; TTD: time to treatment discontinuation Notes: [1] Objective response rate, defined as the sum of partial responses and complete responses, was assessed during the line of targeted therapy subsequent to IO treatment. The total number of patients assessed was 116. [2] VEGFR TKI included axitinib, sunitinib, cabozantinib, pazopanib, bevacizumab, and sorafenib. [3] mTORI included everolimus and temsirolimus.


Subsequent to IO therapy, VEGFR TKI pts had significantly longer adjusted TTD than mTORI pts. When larger sample sizes are available for TT, further examination of sequences is warranted.

Clinical trial identification

Legal entity responsible for the study

Pfizer, Inc.


Pfizer, Inc.

Editorial Acknowledgement


R. McKay: Research funding: Pfizer and Bayer; Ad board: Janssen, Novartis. U.N. Vaishampayan: Research funding, Honoraria, and Consulting: Pfizer. A. Hansen: Research funding: Genentech/Roche, Merck, GlaxoSmithKline, Bristol Myers Squibb, Novartis; Advisory board: Pfizer, Roche, Merck, AstraZeneca, Ipsen, Bristol Myers Squibb. F. Donskov: Research funding: Pfizer, Novartis, Ipsen. G.A. Bjarnason: Research funding: Pfizer, Merck; Honoraria: Pfizer, Novartis, Bristol-Myers Squibb, Eisai, Ipsen; Consulting: Pfizer, Novartis, Bristol-Myers Squibb, Eisai, Ipsen; Travel funding: Pfizer, Novartis. B. Beuselinck: Research funding: Pfizer; Speaker’s fee: Ipsen, Amgen, Pfizer. G. De Velasco: Research funding: Ipsen; Consulting or advisory role: Janssen, Pfizer, Novartis, Bayer, Astellas Medivation, Bristol-Myers-Squibb, Pierre Fabre. M.S. Duh, L. Huynh: M. Duh R. Chang: Employee of Analysis Group, which received funding from Pfizer for this project. G. Zanotti, K. Ramaswamy: Employee of Pfizer. T.K. Choueiri: Research funding: AstraZeneca, BMS, Exelixis, Genentech, GSK, Merck, Novartis, Peloton, Pfizer, Roche, Tracon, Eisai; Consulting and Advisory Role: AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Ipsen. D.Y.C. Heng: Consultancies and Honoraria: Pfizer, Novartis, BMS, Ipsen. All other authors have declared no conflicts of interest.

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