Sumanta Kumar Pal, MD
The treatment landscape of renal cell carcinoma (RCC) is changing at a remarkably fast pace, says Sumanta Kumar Pal, MD.
“It’s incredible to see just how quickly the field of immunotherapy is evolving,” he said. “I definitely think there will be a lot of interest over the next couple of years in looking at the outcomes of some of these trials that combine checkpoint inhibitors, or potentially look at pairings of VEGF inhibitors with checkpoint inhibitors.”
Among these many advancements, the field has also seen the FDA approval of the combination of lenvatinib (Lenvima) and everolimus (Afinitor) in May 2016 as a treatment for patients with advanced RCC following prior antiangiogenic therapy.
Cabozantinib (Cabometyx) received its own FDA approval in this setting as well in April 2016, following the results of the phase III METEOR trial, in which the agent demonstrated a 42% reduction in the risk of progression or death compared with everolimus in patients with advanced RCC.
In an interview with OncLive
, Pal, medical oncologist, assistant clinical professor, Department of Medical Oncology and Therapeutics Research, co-director, Kidney Cancer Program, City of Hope, delves into the recent progress seen in this rapidly growing field, and sheds light on some of the therapeutic options currently available for patients with RCC.
OncLive: What were some of the main highlights from your presentation?
: We had a great opportunity at this year’s meeting to highlight our adjuvant clinical trial of atezolizumab (Tecentriq). The study is going to take patients with high-risk or metastatic RCC who have been fully resected and will randomize them to either atezolizumab for a year, or placebo.
What is the potential impact of a study like this, and what are you thinking in terms of the overall potential impact of atezolizumab if it is approved in this paradigm?
There have been multiple efforts to demonstrate the benefit of therapy in the adjuvant setting. We can think of 6 to 7 clinical trials that have been done using so-called VEGF inhibitors. To date, the results that we have, I would say, are actually somewhat disappointing.
We do have the phase III ASSURE trial, which is reported out by the US cooperative groups, and that study yielded a negative result. We also have the phase III S-TRAC clinical trial, which is led by Pfizer, and although that study demonstrated a delay in tumor recurrence, we still don’t really see a signal of overall survival (OS). I actually think that immunotherapy may potentially overcome that hurdle.
Are you thinking that some of these combination strategies looking at immunotherapy with VEGF inhibitors will enhance activity? Is there any synergy there?
If we’re just talking about the adjuvant setting in this scenario, I think it might be a little too early to start exploring combinations. Right now, I think that the key in the adjuvant setting is really to demonstrate that there are improved outcomes, but at the expense of very limited toxicity. That’s one of the challenges with both the S-TRAC and ASSURE trials. I think that both of those studies demonstrated a fair amount of toxicity in the adjuvant setting. What we’re hoping to do with single-agent immunotherapy, as opposed to a combination, is really yield some benefit and survival and recurrence rates, but also limit the scope of toxicity that patients are experiencing.
What about immunotherapy in the preoperative setting?
There are 2 clinical trials in this space. One is the phase III trial of atezolizumab, which is purely an adjuvant study that I’m involved in the leadership of. There’s also a study through the Eastern Cooperative Oncology Group (ECOG) called the PROSPER trial, which is looking at a short duration of nivolumab (Opdivo) therapy, followed by surgery, followed by extended nivolumab. The comparison there is to observation, not to placebo.