As the ASCO Scientific Sessions of 2017 recede on our calendars, what will be our “take-home” messages? Will we see these sessions in much the same way we view objects in the rear view mirror of our vehicle, as “closer than they actually appear”? In other words, we might speculate as to how close we are to approaching the time when trends observed at ASCO actually have translational impact on our practices.
Much of this is already happening, so don’t look now, but your practice is changing as we speak, and what we see retrospectively from ASCO is already having a sharp impact on how we treat RCC. Here are some quick snapshots from the meeting and general observations:
Adjuvant therapy. We know that a recent New England Journal of Medicine article demonstrated that sunitinib prolongs progression-free survival (PFS) when compared to placebo in high risk, resected patients. The PROTECT trial, as reported at ASCO demonstrated the intent-to-treat analysis was negative but patients who received pazopanib at full doses showed a hazard ratio significantly less than placebo. This suggests that we may need to give targeted agents at full doses in the adjuvant setting to achieve the full impact.
Landscape of treatment. We have a series of drugs available for sequencing—there are TKIs, followed by immune-oncology (IO). Clearly, there are trials that continue to change the landscape. For example, CABOSUN is a trial that compared cabozantinib and sunitinib in the frontline setting with some demonstrated benefit with respect to PFS and OS. If cabozantinib receives regulatory approval, that might change the landscape. The upfront IO combinations or IOs and targeted therapies as illustrated at the 2017 ASCO meeting will be the kinds of trials that will change the landscape in the future.
Immuno-oncology. As we understand the interaction between cancer and the immune system, we recognize that single checkpoint inhibitors have great efficacy, but probably combinations are better, whether it’s IO-IO, or IO and targeted therapy or IO and a novel therapy. In 5 years we will look back and say that the 1990s and 2000s were the era of targeted therapy, but beyond that we are likely to say that IOs are a better replacement.
Sequencing of therapy. In the frontline, the targeted agent could be pazopanib or sunitinib or a clinical trial. In the second line we have much con-troversy because we have a series of drugs, many of which have demonstrated both progression-free and overall survival benefits compared to mTOR inhibitors but have never been compared to each other. In my practice, I tend to use nivolumab first as the second line therapy because I am trying to obtain that tail of the curve and an improvement in overall survival. I reserve agents like cabozantinib and everolimus but that may change depending on how the CABOSUN trial is viewed at a regulatory level and how these other IO combinations come forward.
Take-home on treating kidney cancer. The key to kidney cancer treatment is to tailor a patient’s therapy and the schedule. In patients who can receive full doses, you want to be sensitive to their co-morbidities, because comorbidities limit our ability to give full doses. You want to make sure you address the toxicities associated with targeted therapy—persistently and throughout their course. I tell my patients when I first see them that the beginning of the treatment will be a bit more difficult until we get a handle on toxicity specific to them. Over time, we manage it quite well—we change schedule, we try not to modify dose, we pick patients appropriately and try to match the patient, regimen and the opportunity for best outcome.
Robert A.Figlin, MD