PracticeUpdate: Haematology & Oncology

EUROPEAN SOCIETY OF MEDICAL ONCOLOGY 2016 CONGRESS 24

Dr Toni Choueiri on clinically impactful newRCC data at ESMO 2016

Dr Pal: You’re presenting results from the CABOSUN clinical trial… tell us some of the rationale for pitting sunitinib against cabozantinib. Dr Choueiri: I think this is an amazing unmet need and the National Cancer Institute and the Alliance GU Committee, under the leadership at that time of Eric Small and nowMichael Morris, did recognise this important unmet need, the intermediate and poor-risk population. …One of the unmet needs was in front-line untreated patients can you do more than VEGF receptor blockade. And sunitinib as you know is the most commonly used and highly effective drugs front-line. We have cabozantinib in mind because one of the biology about cabozantinib is that the drug not only inhibits the VEGF receptor, but does inhibit other tyrosine kinases such as MET and Excel, and these we know now are involved in making mechanism of resistance and escape the VEGF receptor inhibitor. There is significant pre- clinical data, and at that time there was a trial that showed cabozantinib as active in later line of treatment. So we launched this study. It’s a smaller study, a randomised phase 2 but well-powered for the primary endpoint of progression-free survival in a population of metastatic RCC of unmet need, which is 70 to 80% of everyone. This is the population of intermediate and poor-risk renal cell cancer. Dr Pal: I would imagine that this study is going to have a dramatic impact on how we think about front-line therapy. But one interesting conundrum that I see is that many of the front- line trials that we have designed right now pit sunitinib against a combination of either IO and VEGF inhibitor or two IOs together. What are your thoughts there? Should we be looking at combinations with cabozantinib now? Dr Choueiri: I think it’s very possible we should because the field is moving very, very fast and there is data. There is also pre-clinical data, not just that cabozantinib works and the IO works so the combination should work, which makes sense, but also there’s pre-clinical data of synergy with cabozantinib on the immune system. There is a decrease in the Tregs which impair the immune response and there’s an increase in CD8 T cell, so together they make more sense also rather than just clinically, but they make more sense biology-wise. Dr Pal: Another hot topic at this meeting is

adjuvant therapy for renal cell carcinoma; first time that we’re going to see some positive data from an adjuvant trial in the S-TRAC Study. Not knowing the data associated with the trial, is disease-free survival a relevant endpoint in this setting, or should we be setting the bar higher to overall survival? I know it’s a common concept in oncology, what do you think? Dr Choueiri : This is a great question. I think when the study was designed disease-free survival was an acceptable endpoint that would not take many, many years to happen based on events. But this is a tough, tough area and I would say it’s going to be, beside the combination and what the front-line is going to show on new target, it’s going to be an area the next 6 to 12 months of intense discussion among experts because we do have a study. Another cooperative group study with Dr Naomi Haas from ECOG we all participated in where the study was completely negative, even on subgroup analysis in high-risk patients which is what S-TRAC is, there was no difference in disease-free survival or overall survival. So we need to see the data. I would be certainly more convinced if the toxicity was acceptable and if there are at least a trend in overall survival because at the end of the day with surgery alone you can cure these patients. Remember this is not versus delayed sunitinib; we don’t know what happens to the placebo arm. So delaying progression, is that acceptable if there is no overall survival and let’s say decreased quality of life, it remains to be seen, but let’s not forget that we, with surgery alone we can cure patients. So we need to look at the study. It definitely could be practice changing, but it has to take in account the ASSURE trial, and of course there are two studies in the adjuvant setting that finished accrual with pazopanib and another was sorafenib. So if these two studies are negative let’s say, then what is going on, we have to ask ourselves. So, look forward to seeing the data.

Sumanta Pal MD, speaks with Toni Choueiri MD (above), Director of the GU Oncology Program, Dana- Faber Cancer Institute, on cabozantinib and adjuvant therapy in metastatic renal cell carcinoma.

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Dr Sumanta Pal is an internationally recognised leader in the area of genitourinary cancers. He is the Co-Director of the City of Hope Kidney Cancer Program in

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Sanofi Genzyme Gaucher disease

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Seqirus Palexia SR A Menarini Abstral

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California and is the head of the kidney and bladder cancer disease team at the institution.

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PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY