ASCO 2021: Renal cancer roundup

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Published: 4 Jun 2021
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Dr Bradley McGregor - Dana-Farber Cancer Institute, Boston, USA

Dr Bradley McGregor speaks to ecancer about the key studies regarding renal cancer at ASCO 2021.

He initially discusses the KEYNOTE-564 study regarding pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma. Dr McGregor then mentions the KEYNOTE-426 study saying that with a median follow-up of 42.8 months, this is the longest follow-up of an anti-PD–1/L1 immunotherapy combined with a VEGF/VEGFR inhibitor for first-line RCC. These results show that pembro + axitinib continues to demonstrate superior efficacy over sunitinib concerning OS, PFS, and ORR, with no new safety signals.

Dr McGregor also discusses the CANTATA trial and studies regarding non-clear cell renal carcinoma. To conclude, he discusses the trials in progress and what we can look forward to in the future.

KEYNOTE-564 Trial
KEYNOTE-426 Trial
Single agent nivolumab plus cabozantinb in a phase II Trial for renal cell carcinoma

It’s been another busy ASCO for advances in renal cell carcinoma. The most practice-changing abstract was a presentation by Dr Choueiri looking at the use of pembrolizumab in the adjuvant setting for high risk renal cell carcinoma using a year of adjuvant pembrolizumab versus placebo showing a marked improvement in disease free survival. Certainly this will be practice-changing for our patients and will offer a novel approach in the adjuvant setting. We’ll have to think about how this is going to change therapy down the line in the first line setting.

Undoubtedly, aside from that, there are other advances in the treatment of renal cell carcinoma presented at ASCO 2021. One of the most notable abstracts was the long-term follow-up for KEYNOTE-426. Again this was a randomised phase III trial looking at the combination of pembrolizumab and axitinib versus sunitinib in those patients with metastatic clear cell renal cell carcinoma. At ASCO 2021 we had the long-term follow-up with a median duration follow-up of over 42 months. What we see with this updated analysis that compares sunitinib with the combination of pembrolizumab plus axitinib is improved overall survival with a hazard ratio of 0.73. We actually are seeing the median duration of overall survival has been reached at 45.7 months versus 40.1 months and the median progression free survival was improved at 15.7 versus 11.1 months. Remarkably, the 42 month overall survival rate was near 60% with the combination which is quite impressive when you think about where we started with renal cell carcinoma five or ten years ago. The response rate was maintained at close to 60% with the combination and the CR rate was at 10% versus 3.5%. So this is certainly very interesting data. It’s the longest term follow-up we have for any VEGF/IO combination with that median overall survival improved at 45.7 months. So this will give us some data as we look towards the longer term follow-up coming from nivolumab and ipilimumab to really look at these different regimens and offer some context as we discuss these with our patients.

Obviously this is great for the front line setting now we have multiple combination regimens that improve survival in the front line setting but we’re always looking for novel approaches. One of the things we’re most excited about was the glutaminase inhibitor with telaglenastat. At ASCO 2021 we saw the presentation for the CANTATA trial which was looking at cabozantinib plus telaglenastat versus placebo plus cabozantinib and whether there’s a lot of hope for this. Unfortunately the trial was a negative trial with no improvement in progression free survival at 9.2 months versus 9.3 months. So whilst this is obviously a very hopeful trial and the authors should be commended for pursuing this, unfortunately it’s a negative trial and certainly we need to continue to do better in the second line setting. The trial did give us some interesting data just looking at the activity of cabozantinib in the second line setting in the modern era. So these are obviously some important insights into the treatment of patients with metastatic renal cell carcinoma.

Beyond clear cell disease one of the areas where we need to continue to improve is in those patients with non-clear cell or renal cell with variant histology where we know that despite our advances in clear cell patients with non-clear cell carcinoma have a worse prognosis than their clear cell counterparts. We saw multiple abstracts and presentations focussing on these patients. We saw data for single agent nivolumab in a phase II trial which compared to what we saw with pembrolizumab [?? 3:55] showed a response rate around 15% for single agent in patients with non-clear cell renal cell carcinoma. We notably saw data for nivolumab plus cabozantinib presented by Dr Lee et al and this looked at the combination of nivolumab plus cabozantinib in patients with variant histology renal cell carcinoma. There are two cohorts – those with unclassified papillary or translocation as well as those with chromophobe. In that first cohort, those unclassified papillary translocation, which probably is 48% with a median progression free survival of over a year which is quite remarkable when we think of other VEGF/IO combinations. We have the combination of atezolizumab and bevacizumab with a response rate less than 30% in that broader population of variant histology renal cell carcinoma. So that’s obviously very intriguing and it’s the foundation for other trials that are ongoing. Dr Lee has a trial in progress looking at the combination of lenvatinib and pembrolizumab and we actually have a trial in progress looking at the combination of cabozantinib with nivolumab and ipilimumab in those patients with variant histology renal cell carcinoma who received up to one prior line of therapy. So obviously very excited about improving the care for these patients in this unmet population.

So overall ASCO 2021 has certainly offered us advances in the treatment of renal cell carcinoma and will certainly provide a building block for future trials and ideas. Thank you for your attention.