Renal Cell Carcinoma: KOL Insight [2018]

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Publication Date:
June 2018
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RCC: A new era of IO-based combination therapy

The recent FDA approval of BMS’ Opdivo/Yervoy has pioneered a new immuno-oncology (IO)-based combination approach to the first-line treatment of RCC. How do KOLs view Opdivo/Yervoy and the potential emergence of a host of IO-based combination approaches in the late-stage pipeline (e.g. Merck & Co.’s Keytruda/Pfizer’s Inlyta; Roche’s Tecentriq/Avastin, Merck Group/Pfizer’s Bavencio/Inlyta)? As the first-line treatment paradigm shifts, how will use of Pfizer’s Sutent and Novartis’ Votrient evolve and what therapies will dominate in the second-line setting? Sutent was recently approved in the adjuvant setting, but how do KOLs rate the chances of success for VEGF TKIs versus IO agents, such as AstraZeneca’s Imfinzi, to succeed as adjuvant therapies?

Twelve of the world’s leading KOLs from the US and Europe offer candid insights on twelve marketed drugs and five Phase III therapies.

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Top takeaways

  • BMS’ Opdivo/Yervoy combo regimen recently received FDA approval for the first-line treatment of intermediate- or poor-risk, advanced RCC. How do KOLs view the clinical profile of this combination and how widely used will it be?
  • In light of Opdivo/Yervoy’s first-line approval, how will the use of VEGF TKIs Sutent (Pfizer) and Votrient (Novartis) be impacted? And what therapies will dominate in the second-line setting? 
  • A multitude of VEGF-TKI/IO combinations are in development for treatment-naïve, advanced RCC. How do KOLs rate their chances of success and what could differentiate between them?
  • Pfizer’s Sutent was recently approved in the adjuvant setting. What are KOLs’ expectations of Sutent’s uptake, and the overall potential for VEGF TKIs to succeed in this setting?
  • Trials underway investigating c-MET inhibitors may address unmet need in patients with papillary RCC (pRCC). How do KOLs view the prospects of c-MET inhibitors, including Exelixis/Ipsen’s Cabometyx and AstraZeneca’s savolitinib, in pRCC?
  • The Phase III IMmotion151 trial of Tecentriq/Avastin was successful in meeting its co-primary endpoint of investigator-assessed PFS in PD-L1-positive patients. How do KOLs interpret these data, and how do they view this combination compared with other pipeline IO-based regimens?
  • The next few years will see a rapidly evolving treatment paradigm as new therapies are launched. How will oncologists navigate this increasingly complex treatment landscape and what key factors will guide drug selection?
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“In advanced disease the TKI-based combinations certainly seem to have the right balance of activity and tolerability. Whether they can produce the durability of response that nivolumab/ipilimumab can remains to be seen.”
US Key Opinion Leader

“It’s been an incredible time, from not having anything but cytokines pre-2005, to VEGF TKIs, and now IO in combination. The landscape is moving towards being IO-oriented. My initial expectation was that it was going to be a pure IO approach, but I think I am being proven wrong by the initial data from combination trials.” 
US Key Opinion Leader

Sample of therapies covered

Marketed Therapies

  • Opdivo (nivolumab; Bristol-Myers Squibb)
  • Yervoy (ipilimumab; Bristol-Myers Squibb)
  • Sutent (sunitinib; Pfizer)
  • Votrient (pazopanib; Novartis)
  • Inlyta (axitinib; Pfizer)
  • Cabometyx (cabozantinib; Exelixis/Ipsen)
  • Nexavar (sorafenib; Bayer/Amgen)
  • Lenvima/Kisplyx (lenvatinib; Eisai)
  • Avastin (bevacizumab; Roche)
  • Fotivda (tivozanib; AVEO Oncology/EUSA Pharma)
  • Afinitor (everolimus; Novartis)
  • Torisel (temsirolimus; Pfizer)

Phase III Therapies

  • Keytruda (pembrolizumab; Merck & Co.)
  • Tecentriq (atezolizumab; Roche)
  • Bavencio (avelumab; Merck Group/Pfizer)
  • Imfinzi (durvalumab; AstraZeneca)
  • Savolitinib (AZD-6094; AstraZeneca)

KOLs interviewed

KOLs from North America

  • Michael B. Atkins, Deputy Director of the Georgetown Lombardi Comprehensive Cancer Center, and the Scholl Professor and vice chair of the Department of Medical Oncology at Georgetown University Medical Center, Washington DC
  • David A. Braun, Fellow in Hematology and Oncology, Brigham and Women's Hospital, Internal Medicine, Boston, MA
  • Robert A. Figlin, Professor of Hematology-Oncology/Director, Division of Hematology/Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
  • Saby George, Associate Professor of Oncology, Roswell Park Comprehensive Cancer Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY
  • Robert J. Motzer, Professor of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
  • Brian I. Rini, Professor of Medicine, Lerner College of Medicine, The Cleveland Clinic Taussig Cancer Center, Cleveland, OH

KOLs from Europe

  • Peter F. A. Mulders, Professor and Chairman of the Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands
  • Hardev Pandha, Professor of Urological Oncology, University of Surrey, and Consultant at Guildford Nuffield Hospital and St Luke’s Cancer Centre, Guildford, Surrey, UK
  • Giuseppe Procopio, Professor of Medicine, Head of the SS Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Naveen Vasudev, Clinical Associate Professor and Honorary Consultant in Medical Oncology, Faculty of Medicine and Health, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
  • Leading German KOL, Professor of Oncology, Department of Internal Medicine, a major university hospital, Germany
  • Leading German KOL, Professor and Vice Chairman, Department of Urology, a major university hospital, Germany

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