Dr. Braun and Dr. Kenney on unmet needs in kidney cancer

In this interview, David Braun, MD, PhD, and Patrick Kenney, MD, describe their practices and touch on unmet needs in kidney cancer treatment. Braun is an assistant professor of medicine (medical oncology) and of pathology and urology at Yale School of Medicine, New Haven, Connecticut as well as a Yale Cancer Center member. Kenney is an associate professor of urology at Yale School of Medicine in New Haven, Connecticut and medical director of Smilow Cancer Hospital in Greenwich, Connecticut.

Transcription:

Please describe yourself and your practice.

Braun: My name is David Braun. I'm an assistant professor here in the departments of medicine, pathology, and urology. I'm really a physician scientist that focuses on the understanding and care of patients with kidney cancer. I spend a lot of time in the clinic caring for patients with different stages of disease and different types of kidney cancer, but leaning more toward patients with more advanced types of kidney cancer. In the laboratory, we study how the biology of the tumor works, and ultimately how we can think about better ways to treat it.

Kenney: My name is Pat Kenney, and I'm a urologic oncologist. I'm a surgeon for the urinary tract. My clinical practice focuses entirely on kidney cancer. I do open and robotic surgery for tumors of the kidney, including things like removing tumor from the vena cava. And that's something that we do with open or robotic surgery here. And I collaborate with Dr. Braun on research efforts in the lab, as well as clinical trials.

Braun: One of the goals that we've really tried to work on together is that integration between basic science in the laboratory and clinical impact. It's really bi-directional. Part of that is trying to understand from every case of kidney cancer we see, is there something we can learn? And so together, we've worked on establishing a program for studying those tumors here in the laboratory, understanding why the immune system recognizes or doesn't recognize it, and how we can modulate things...But then the goal is ultimately for both of us to bring this back to the patients. We've been working on a variety of clinical trials that help to improve clinical care for patients with kidney cancer. That's in a number of spaces. That's both in the adjuvant space, so patients who hopefully have a cure curative surgery, but might have a high risk of recurrence afterwards, but also in the more advanced disease setting as well.

Kenney: I think it's very important to note that our patients have also been great partners in this. We've had a tremendous response from patients who are willing to donate their tissue of the cancer that was removed for research. We've accumulated a really fantastic resource of specimens that we're able to interrogate to learn more about the disease process.

What are some of the biggest unmet needs in kidney cancer?

Kenney: There's a variety of needs. We've made great progress in the field. Something that as a surgeon, we have changed really dramatically over the past decade or 2 is how we do surgery. Even in the 10 years I've been in practice here at Yale, the way I do things in the operating room is very different. We very commonly will do robotic surgery for something that used to be considered only capable of being done with open surgery like complicated retroperitoneal lymph node dissections, IVC tumor thrombectomy, all done robotically now. The thing that's really humbling though, is that those advances in surgery and surgical technique help people as they recover from surgery, but have not impacted people's cancer outcome. We don't save lives by doing robotic surgery; we make their lives, for a brief period of time, better. What we need is continued work on integrating surgery and systemic therapy. We have an exciting new development in the field of an agent that's used in the adjuvant setting that we've heard that there's improvement in overall survival. We don't yet have a complete set of information, but a very exciting development for many of our patients. But it's only really a small percentage of patients who seem to benefit from that drug, and there's still a significant number of patients who are at risk for recurrence. We need better drugs, better thought, and perhaps different approaches to the treatment in the adjuvant setting. And then continued work on surgical technique. From a surgeon's perspective, those are our priorities. But obviously, there are very different priorities for people with advanced disease.

Braun: That's absolutely right. And it's amazing to see the progress on the medical front as well. If you dive into the data from not decades and decades ago, but from 10, 15, 20 years ago, the average time from diagnosis to death for advanced or metastatic kidney cancer was about a year. Now, it's more like 4 to 5 years. That's a tremendous advance, and has been really built on the backbone of targeted therapies, and more recently, immune checkpoint inhibitors. But even with that advance, we still understand that the majority of patients with advanced kidney cancer will unfortunately still die of their disease. We need to do better, and there are a lot of ways to do that. We now know that immunotherapy is an incredibly powerful tool, and I think with the current ones, we're just scratching the surface. We're really nonspecifically just releasing the brakes on the immune system. But there are ways to add a gas pedal to modulate the immune system further, and I think, really critically, to add a steering wheel to say, rather than nonspecifically turning on the immune system, can we really direct it toward a target? That's through things like antigen-directed therapies, vaccine-based approaches is 1 example. And so that's something that we have a lot of interest in, as well, is really finding what are the effective targets for the immune cells to recognize and how can we use that information to really modulate the immune system and add that steering wheel. That's the ultimate goal. I think a lot of the current trials are important in building on existing therapies incrementally, and that provides really meaningful benefits for patients, both in terms of quality and quantity of life, but we also need a few more paradigm leaps as well. What are the next generation of immune therapies that are going to get us from better outcomes to true cure for a larger number of patients?

This transcription was edited for clarity.