Know Your Investigator

June 2021

HOST: Dr. Chadi Nabhan

GUEST: Dr. Neeraj Agarwal

The interview took place in April 2021.

: Welcome Neeraj to our quarterly Caris Connection e-Newsletter. For those who don’t know you, tell us a little about yourself.

AGARWAL: I’m a medical oncologist who specializes in genitourinary (GU) cancer – prostate, kidney, and bladder. I consider myself a clinical and late translational investigator. I’ve spent a lot of time in clinical trials from Phase-I to Phase-III and have had the privilege of steering many of them. I like to describe myself as an investigator who is passionate about developing new drugs and getting better, more tolerated treatment options for our patients with GU cancers to not only improve survival but also quality of life.

NABHAN: Recently you added an additional role to what you’re doing as an investigator. Tell us about this new promotion you received at the Huntsman Cancer Institute (HCI).

AGARWAL: I was asked to take on this new responsibility as Senior Director at the University of Utah and Huntsman Cancer Institute. This is a Cancer Center’s senior leadership role (also called an Associate Director at many cancer centers) that reports directly to our Cancer Center Director, Dr. Cornelia “Neli” Ulrich, an internationally renowned translation researcher. My job will be innovating and expanding clinical research reach within the cancer center.

NABHAN: How do you divide your time with all the responsibilities that you have?

AGARWAL: The best part about being a clinical and a late translational investigator is that your research happens in your clinic. I’ve been very fortunate to have such a supportive group of people around me and my bosses have all been very supportive over the last decade. You have to have adequate support, whether it’s in the form of scribes, nurse practitioners, or nurses. A Cancer Center Director or Division Chief shouldn’t expect to have their faculty perform and produce at high levels without being given the necessary support. We are only as good as the support we have. My favorite statement that I give anyone who asks for my advice is: “Seek support.” That is the most important aspect moving forward. In my case, I have had fantastic support in my clinic in terms of nurses, nurse practitioners, pharmacists who help me with drug interactions, and then our clinical trials office – I think we have the best clinical trials office in the country led by Dr. Theresa Werner.

NABHAN: As a GU oncologist, do you see the field migrating where you have to see either prostate or kidney or bladder?

AGARWAL: In my view, unless you have 10 dedicated GU medical oncologists in your program you should not even try to sub-specialize (in prostate, kidney or bladder). Patients are going to come to the clinic to see one of the urologists. And let’s say a patient has localized bladder cancer and needs to have a conversation about neoadjuvant chemotherapy but you only have two GU oncologists who specialize in bladder cancer and neither of them are in the clinic that day. Who is going to talk to the patient? If you can’t see the patient, the patient will go to somewhere else. Or what’s worse is that they won’t get the neoadjuvant chemotherapy they need. For now we are seeing prostate, kidney and bladder. In our program we all are GU medical oncologists.

NABHAN: How do you see the field today and where’s the intersection of precision oncology and genomic medicine when it comes to GU cancers? Also, how has it evolved over the years?

AGARWAL: As of now, every patient with metastatic/advanced prostate cancer, should be undergoing comprehensive genomic profiling of their tumors. Not only do we have approved drugs available in the clinic which are based on underlying molecular targets (those are PARP inhibitors for people who may not be aware), but this is just a start. We have multiple trials that are open for newly diagnosed hormone sensitive prostate cancer patients which are based on underlying molecular targets. So there’s no reason why every patient with metastatic prostate cancer or advanced prostate cancer shouldn’t be discussing comprehensive genomic profiling on the first day we see them. Every patient should eventually be undergoing comprehensive genomic profiling. How many are actually doing it? It’s unfortunate to see only a minority of these patients are undergoing comprehensive genomic profiling. I think the challenge is how to bridge this gap – how to make everyone aware that we should not wait to do this sequencing until the onset of castrate resistant disease or after exhausting all options. That is often too late for most patients. This is one challenge we have.

The second is bladder cancer. We already have a targeted therapy (erdafitinib) approved for patients with metastatic bladder cancer. Recently we published a paper with Dr. Petros Grivas, Dr. Monty Pal and Dr. Umang Swami that looked at how many patients in the US with metastatic bladder cancer get first line therapies, second line therapies, and third line therapies. With the caveat of this being a little older data set in 2018, we saw less than half of the patients ever receive first line systemic therapy. Therefore we lose half of the patients at the time of diagnosis because the surgeons don’t think there are good therapies out there for their patients and they’ll tell that to their patients. After that it’s roughly 18% of the patients that get second line therapy and 6% of patients that get third line therapy. We know that once these patients have disease progression we lose more than half of them because of various reasons including urinary obstruction and renal failure. Bladder cancer is an aggressive disease and many bladder cancer patients have disease progress so quickly that they lose their performance status. Thus without waiting for them to experience disease progression on systemic therapies, we should be sending out comprehensive genomic profiling for all of these patients whenever we see them for the first time, especially with trials with FGFR inhibitors coming into localized bladder cancer settings.

NABHAN: Holistically, do you think some of these mutations and genomic aberrations that we see in advance disease exist in early stage disease?

AGARWAL: I would say less than 10% with localized bladder cancer have these alterations, but the chances that you will lose those patients or their original biopsies by the time they develop metastatic disease is very high. In the context of prostate cancer, this is based on my personal experience of being one of the steering committee members of the PROFOUND trial. I would rather order the sequencing up front and then if needed, do the sequencing again at the time of disease progression. I’m a strong proponent of sequencing the tumors of patients when I see them for the first time. In fact, in my clinic we have an order sheet which includes CBC, CMP, CT scans, bone scans, and now comprehensive genomic profiling for all patients with metastatic prostate cancer. I think that is the only way to optimize our patients’ eligibility for these highly, well-tolerated targeted therapies down the line on or off trials.

NABHAN: Do you see the same trend in kidney or is it less valuable for kidney?

AGARWAL: In kidney cancer, we already have ongoing trials but we do not have any targeted therapy in the clinic. If you ask the question – “do we need sequencing up front or not?” I would say the answer is “yes.” I talk to every patient with any advanced cancer, whether it’s adrenal cancer or penile cancer or kidney cancer. We may not have targeted therapies approved for them, but the results of the comprehensive genomic profiling test may open new avenues of treatment for these patients through clinical trials. So in my view, every patient with any advanced cancer should have the opportunity to hear about the pros and cons of tumor genomic profiling from their providers.

NABHAN: What do you do for fun and how do you manage the work-life balance?

AGARWAL: That’s a fantastic question. I have the most supportive family I can think of. I think all of us who are passionate investigators, for us this is the best part of our life – investigation. But we do have other activities like hiking, biking, traveling … and I think all of this is only possible if we have a very supportive family. My wife is a very busy hematopathologist/molecular pathologist and has a very successful career. The key is to have great support from the family and be helpful to each other – that’s where it starts.

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Dr. Neeraj Agarwal

University of Utah
Huntsman Cancer Institute (HCI)