GU Cancers 2018 | Promising results for axitinib and pembrolizumab in advanced renal cell cancer

Michael Atkins

Michael Atkins, MD, of Georgetown University, Washington DC, outlines the results of the study of VEGF inhibitor axitinib in combination with pembrolizumab for the first-line treatment of advanced renal cell cancer (NCT02133742). Dr Atkins goes onto explain the next steps required for this result to impact treatment, and eagerly awaits the results of the KEYNOTE-426 trial (NCT02853331). This interview took place at the 2018 Genitourinary Cancers Symposium in San Francisco, CA.

Transcript (edited for clarity):

We designed a Phase Ib trial with two phases; the first was a dose-finding phase which used axitinib and pembrolizumab together at full doses, and we found in the first 11 patients that it was well tolerated and we didn’t see some of the toxicity problems that we’re seeing with the less selective TKIs combined with anti-PD1, so we didn’t see significant liver toxicity or fatigue or patients not being able to stay on treatment. And so that led us to the dose expansion cohort of another 41 patients, where even though there was about a 64% incidence of grade 3 toxicities over the 18 months to 2 years of time on therapy, most patients were able to stay on trial and we didn’t see liver toxicity or significant immune related toxicities to a major degree, and only 9 of the 52 patients had to stop treatment due to toxicity. From an efficacy standpoint we saw that there was a 73% overall response rate, 8% complete response rate and a median progression-free survival of 20.9 months, all record numbers for frontline treatment of patients with metastatic kidney cancer. In addition of the overall survival day that were immature only 6 patients had died; 4 who died of disease and 2 who died of unrelated causes at the time the study was looked at, and there were 90% of patients still alive at 18 months.

Right now these results are the best results ever reported for the treatment of kidney cancer, but they’re not definitive; they’re a single arm, Phase Ib expansion cohort with 52 patients and could have been influenced by a variety of factors including the patient population enrolled in the trial. So in order for this result to impact treatment, we need to see a Phase III trial to see how this combination compares to a VEGF receptor TKI followed by an anti-PD1. And that trial, which is the KEYNOTE-426 trial, has been underway for over a year and should have recently reached its accrual goal and so we’ll see the results sometime in the next couple of years. But what these data suggest is that it’s very likely that that trial will be positive for response rate and PFS endpoints, and therefore it’s likely that this treatment option as well as a lot of other trials that are looking at the same type of agents in combination will likely become available for patients with kidney cancer.

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