Dr. Choueiri’s study found that in an updated analysis of the CABOSUN trial (cabozantinib versus sunitinib), cabozantinib significantly increased PFS per independent review committee compared with sunitinib as initial targeted therapy in patients with mRCC. Additionally, cabozantinib resulted in improved OS compared to sunitinib, although these results were not statistically significant. Dr. Porta summaries a number of highlights from this study: (i) the CABOSUN data are convincing, given that PFS survived an independent review committee and the OS data are clinically relevant, albeit not statistically significant; (ii) this may be a new standard of care option for intermediate and poor risk RCC, however the translation may not be straightforward considering the small number of patients and the breaking findings regarding CheckMate214 showing significant OS benefit of nivolumab + ipilimumab vs sunitinib in the same disease space .
Dr. Powles’ study found that updated efficacy (RECIST v1.1) confirmed the encouraging activity of atezolizumab + bevacizumab in PD-L1+ first-line mRCC, with no new safety signals. Data per imRECIST, compared with RECIST v1.1, showed benefit of atezolizumab + bevacizumab in PD-L1+ and intention to treat patients and may contribute to our understanding of the clinical activity of cancer immunotherapy in mRCC. Dr. Porta notes that (i) it is time to accept that imRECIST is ready for primetime, considering that it is already used in everyday clinical practice; (ii) we still don’t know how common real pseudo-progression is in RCC. Additional questions: What are the dynamics of the immune response when using immune checkpoint inhibitors with or without VEGFR-TKIs? Is there any immunological effect of TKIs? (iii) we should be starting to use higher PD-L1 expression cutoffs than 1% to improve discriminatory effects, as is already commonly done in NSCLC.
Dr. Bosse’s study found that in their phase I trial, radium-223 combined with pazopanib or sorafenib was safe and well-tolerated. Furthermore, all five bone turnover markers significantly declined with radium-223 combined with pazopanib or sorafenib, suggesting biologic activity in mRCC with bone metastases. Take-home messages regarding this study from Dr. Porta include (i) radium-223 appears to be compatible with VEGFR-TKIs, confirming its safety, which is well known from its CRPC use; (ii) there are caveats, including the lack of a control arm, making it difficult to understand if bone turnover marker changes were due to radium-223, TKI’s or both; (iii) additional endpoints such as reduction in skeletal related event rate, reduction in pain or the use of narcotics would have been more interesting.
Dr. Staehler’s study found that in a post-hoc analysis of S-TRAC data, no new safety signals were identified with sunitinib use in the adjuvant RCC setting. The authors concluded that effective therapy management, including dose reduction/interruption if necessary, is important as it optimizes the possibility of receiving effective treatment. Dr. Porta notes several important conclusions from this study: (i) despite effective therapy management and expertise of treating physicians, only 56% of patients completed the scheduled one year of treatment; (ii) the trade-off between the possible benefit of reducing risk of relapse and treatment related adverse events in the adjuvant setting is completely different from that accepted by metastatic patients; (iii) more than 25% of treatment delays and interruptions in the placebo arm highlights the role of psychological issues with anxiety regarding the risk of recurrence and treatment related adverse events; (iv) psychological endpoints should be added to the next generation of adjuvant trials.
Speaker: Camillo Porta, IRCCS San Matteo University Hospital Foundation, Pavia, Italy
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
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2. Powles T, McDermott DF, Rini B, et al. IMmotion150: Novel Radiological Endpoints and Updated Data From a Randomized Phase II Trial Investigating Atezolizumab With or Without Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma. ESMO 2017 abstr LBA39.
3. Bosse D, McKay RR, Gray KP, et al. Pazopanib or Sorafenib + Radium-223 in Metastatic Renal Cell Carcinoma with Bone Metastases. ESMO 2017 abstr 854.
4. Staehler M, Motzer RJ, George DJ, et al. Adjuvant sunitinib in patients with high risk renal cell carcinoma (RCC): Safety and therapy management in S-TRAC trial. ESMO 2017 abstr 855.
5. Escudier B, Tannir N, McDermott D, et al. CheckMate 214: Efficacy and safety of Nivolumab + Ipilimumab vs Sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. ESMO 2017 abstr LBA5.