1. DiGiulio, Sarah

Article Content

The Journal of Clinical Oncology recently published a special series on new advances and ongoing research in kidney cancer. The journal regularly rotates through topics for its special series collections (to cover practice updates and forthcoming research clinicians should be aware of), but this new series on kidney cancer is particularly timely, noted David F. McDermott, MD, Director of the Cutaneous and Immuno-Oncology Programs at Beth Israel Deaconess Medical Center, Leader of the Dana Farber/Harvard Cancer Center Kidney Cancer Program, and Professor of Medicine at Harvard.

David F. McDermott, ... - Click to enlarge in new windowDavid F. McDermott, MD. David F. McDermott, MD

"Over the last 3 years, investigators have leveraged a growing understanding of kidney cancer biology to target critical pathways and produce durable benefits, even rare remissions, for patients with advanced kidney cancer," McDermott wrote in an overview article he co-authored in the series (2018; doi:10.1200/JCO.18.01198).


McDermott served as a guest editor for the series, helping select the topics covered, recruiting researchers to write the reviews about those topics, and reviewing the articles featured in the series.


McDermott is also co-principal investigator of the NCI Specialized Programs of Research Excellence grant focusing on kidney cancer.


"There are quite a number of new options for patients [with kidney cancer] that are improving survival and, in rare cases, even leading to remission," McDermott told Oncology Times. The articles in this special series cover those advances, as well as the new questions and challenges those advances come with. The series covers new therapy targets that may lead to future improvements, as well as advances in prevention, early detection, and surgical interventions.


"It's really a soup-to-nuts overview on where the treatment of kidney cancer is in 2018," McDermott said. He shared some highlights of the coverage.


1 What makes this special series so timely? What are the highlights in the coverage?

"I think the biggest advance in kidney cancer over the last few years-this is true in all cancer types, but especially in kidney cancer this was the case-is the better understanding of how tumors evade the immune response and how you might be able to overcome those by applying immune checkpoint inhibitors (like PD-1 and PD-L1).


"They were first introduced in the kidney cancer clinics a few years ago for patients who failed kidney cancer treatment and now we're bringing them into the frontline in combination-either combinations with older therapies like VEGF blockades (fusing first-line and second-line therapies). Or we're using [these immune checkpoint inhibitors] in combinations with other immune therapies. And the early results are encouraging.


"We had [nivolumab plus ipilimumab] FDA-approved in April (N Engl J Med 2018;378:1277-1290). And since we started [this article series] a year ago, there have been three other randomized phase III trials that have met their primary endpoint that combine VEGF blockade and PD-1. So in the coming year, there will be several FDA approvals of those combination, which is essentially fusing first- and second-line therapies together."


2 What are some of those still unanswered questions and gaps in the research and evidence?

"The benefits [and new data] are encouraging to patients, but it also presents new questions and challenges. How do you manage the cost? Toxicities? Which patients should receive which combinations? What do you do when patients fail a combination therapy? And I think the average practitioner will be faced with the dilemma of which should I use first? Should I stick with my old standard therapy or should I try these new combinations-and if so, why?


"Also, what are the new targets? Can you bring these new approaches into the adjuvant setting? (That's an area of active research.)


"And decreasing kidney cancer incidence is important. What risk factors can we modify that might reduce the incidence, which is particularly important around the world where they don't have access to any of these treatments. What are the new imaging techniques that are useful?


"What are the genetic predispositions of kidney cancer and the implications for screening and the management of those patients? How can we better stage patients? What are we learning about the different subtypes of kidney cancer and what are these molecular pathways that drive them?


"How do you manage small renal tumors, which are common but not always lethal? How do you manage advanced disease after surgery?


"It's a fast-moving field and we need to focus on the rational application of these new treatments (not just broadly give them to every patient). We need to do a better job of appropriately selecting patients for treatments.


"We want [kidney cancer care providers] to stay focused and tuned in on what's new and what's coming out in journals and at medical meetings, too. The new therapies are not just making statistically significant differences in clinical trials, but they're making clinically meaningful differences for our patients."


3 Are there any takeaways in these articles?

"I think it is important, not just for kidney cancer but for all tumor types, that we balance our approach, not just in the clinic, but also focusing on funding and supporting good basic science research.


"Too often we get focused on new drugs and new targets-which is important. But we still need innovative new ideas that often come from the laboratories. We need to fund those creative scientists who will make the next big discoveries. We're now benefiting from discoveries from 10 and 20 years ago. But we need to keep funding the basic work that may come from many different areas."