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 N||Number of treatment discontinuation for any reason (%)||Median TTD, (95% CI) months||Objective response rate1 N (%)|
|All||184||118 (64)||4.9 (4.0, 5.6)||20 (17)|
|All lines||156||93 (60)||5.3 (4.3, 6.9)||19 (20)|
|2nd line||44||28 (64)||3.8 (3.2, 5.4)||7 (23)|
|3rd line||72||43 (60)||5.7 (4.3, 9.8)||10 (22)|
|≥ 4th line||40||22 (55)||6.1 (4.2, 10.9)||2 (10)|
|All lines||28||25 (89)||2.5 (1.4, 3.4)||1 (5)|
|3rd line||20||19 (95)||2.3 (1.0, 4.9)||1 (6)|
|≥ 4th line||8||6 (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:  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.  VEGFR TKI included axitinib, sunitinib, cabozantinib, pazopanib, bevacizumab, and sorafenib.  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
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.