ANZUP Mini ASM 2020: Renal Cell Carcinoma - UNISoN, What’s Next?

( The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) trial update at the 2020 ANZUP Mini Annual Scientific Meeting (ASM) featured a discussion from Dr. Craig Gedye regarding renal cell carcinoma (RCC). Dr. Gedye notes that immunotherapy in renal cell carcinoma has a long history, starting with cytokine immunotherapy many decades ago. Since then, there has been the advent of various VEGF TKIs, with generally similar results, followed by immune checkpoint immunotherapy, and more recently checkpoint immunotherapy plus VEGF TKIs. The question is how we combine these various therapeutics, with the following figure demonstrating the current landscape:

current landscape of therapeutics

There are many combinations with a plethora of data, but Dr. Gedye notes that there are still many unanswered questions, including:

  • Are these new treatment modalities better than properly used sunitinib?
  • Could the patient take immunotherapy alone?
  • Should we use one or two immunotherapy drugs?
  • Should we use immunotherapy and then VEGF TKI?
  • What is the best immunotherapy plus VEGF TKI combination?
  • Is any combination better than any other?
  • Are there any combinations that are easier to use?

According to Canadian goals for research priorities for kidney cancer, the following three proposals were amongst the top priority: (i) development and evaluation of new effective treatment for patients with advanced kidney cancer of the non-clear-cell variety/subtype, (ii) identification and validation of biomarkers that may be used to predict the response to treatment for kidney cancer, and (iii) identification and validation of biomarkers that may be used for the detection of kidney cancer. British research priorities for patients with RCC are as follows:

  • Selecting the right targeted therapies and immunotherapies, a combination of therapies and optimal therapeutic sequence for individual patients to maximize the quality of life and minimize side effects
  • Management for patient groups that are difficult to treat, and in particular non-clear cell RCC (nccRCC) subtypes
  • Maximize quality of life in all domains
  • Early detection and screening for RCC
  • Personalized treatment to minimize side effects of therapy, increase effectiveness and maximize quality of life
  • Optimizing and personalizing follow up after treatment for RCC
  • Improved prognostic tools

Additional questions that remain to be answered according to Dr. Gedye include (i) which kidney cancer needs to be treated? (ii) Who might have residual disease after surgery? (iii) Who is experiencing recurrence/progression of disease? (iv) Which people with RCC need systemic treatment?

The ANZUP led UNISoN (ANZUP 1602) trial is testing nivolumab followed by ipilimumab plus nivolumab in patients with advanced non-clear cell renal cell carcinoma. This study aims to test two ideas: (i) the activity of immune checkpoint inhibitors in nccRCC, and (ii) the novel sequencing strategy of anti-PD1 immunotherapy, followed by the combination of anti-PD1 and anti-CTLA4 blockade, in people failed by single-agent treatment. Part 1 of the trial accrued 85 patients, and part 2 has 48 patients. This single-arm trial is recruiting patients with locally advanced/unresectable rare variant nccRCC including papillary (type 1/2), chromophobe, sarcomatoid, Xp11 translocation, collecting duct, and unclassified histological subtypes. This trial is powered to distinguish a clinically non-relevant objective tumor response rate of 15% in people taking combination immune checkpoint inhibitor whose cancers are refractory to single-agent PD1, versus a clinically-relevant objective tumor response rate of 30% at a 5% level of significance with 80% power. Currently, this trial is closed to accrual and awaiting follow-up.

Given our current landscape, we are still working to assess which treatment is right for each person. We still have uncertain long-term outcomes, complex toxicities, long-term toxicities, an absence of biomarkers, clinical trials with flawed designs, and a need for real-world patient experiences. Dr. Gedye notes that the ANZUP RCC Horizon meeting will be in February 2021, with objectives including defining the current therapeutic landscape and a strategic direction to improve RCC treatment through ANZUP trials.

Presented by: Craig Gedye, MB ChB, FRACP, PhD, Department of Medical Oncology, Calvary Mater Newcastle, Scientific Advisory Committee, Mark Hughes Foundation, Chair, Scientific Advisory Committee and Renal Cancer Subcommittee, ANZUP Cancer Trials Group, Waratah, Australia

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2020 Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting (ASM), November 29 - 30, 2020 

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