Know Your Investigator

March 2021

Dr. Chadi Nabhan recently caught up with Dr. Charu Aggarwal, Leslye M. Heisler Associate Professor for Lung Cancer Excellence in the Division of Hematology-Oncology at the University of Pennsylvania’s Perelman School of Medicine. She is an active member of the Abramson Cancer Center (ACC) where she also serves as Physician Leader for the clinical research program for Airways Malignancies.

The interview took place in late December 2020.

NABHAN: What got you interested in oncology and specifically lung cancer?

AGGARWAL: When I was thinking of a medical specialty, I was very drawn to oncology from the beginning. After finishing medical school, I did my MPH at the University of Alabama in Birmingham and worked in research within their bone marrow transplant unit. I did this because I was interested in oncology. My first research presentation was an oral presentation as a research assistant at the ASBMT Meeting, which was more than a decade ago, but this was the kind of stuff in which I was interested. Then I went through residency, applied for medical oncology and got into a HEMONC fellowship. I started solid tumor oncology first. With the way our HEMONC fellowship was structured, I got assigned to a full year of solid oncology first, and I immediately appreciated the outpatient aspect of solid tumor oncology of how we’re able to prolong and improve our patients’ lives and overall quality of life. That was also when I started to appreciate the discrepancies in research amongst different cancers, for example, therapeutic differences between breast cancer compared to lung cancer research. That was also the time when we were just coming up to data on the use of pemetrexed in the first line setting, as well as the question of maintenance therapy. I enjoyed my time in the lung cancer clinic and I thought I could make an improvement within the lung cancer disease space.

NABHAN: How do you divide your day? What does that pie chart look like in the life of Dr. Aggarwal?

AGGARWAL: I’m very much a clinician and being a doctor is my job, first and foremost. I’m in clinic one and a half to two days a week, and the rest of my time is spent in research and taking care of administrative responsibilities. I also teach fellows and usually have a fellow or a resident in my clinic. I do inpatient service two to four weeks a year as well. I also lead the clinical trials program within the airways group and make sure we hit our metrics in terms of enrollment in clinical trials, opening the correct kind of clinical trials, and ensuring that our clinical trials are being conducted well. The rest of my time is spent managing my other research projects as they relate to precision medicine.

NABHAN: Tell me the story behind the endowed professorship. That’s so impressive, especially to get that so early in your academic career. How did this happen?

AGGARWAL: I took care of a patient very early in my career in my second year of being an Assistant Professor at Penn Medicine. This patient was a wonderful person who loved to travel, and we would share travel stories since I love to travel too. Unfortunately, she succumbed to her metastatic lung cancer, but we had developed a really good friendship prior to her passing. Two or three years after her passing her husband approached us and told me he was thinking about his will and was really considering giving a gift to support my research. I was taken aback by this because a few years had passed since I took care of his wife, and I wasn’t really expecting his call. Her husband and I had a few meetings and we discussed my research and at that time he wasn’t sure if he was going to proceed with a gift to Penn Medicine or Johns Hopkins where he also had ties.  Ultimately he decided on giving the gift to Penn Medicine. The initial gift was going to be much smaller, but then as we began talking about what the direction the research was going to be, it became very clear that he was going to provide a much more generous gift. He really wanted to create a legacy to support his wife and that’s when the idea of making an endowed position came into play. He was very committed to supporting the research that I was doing and also creating a legacy for his wife. That’s how the endowed professorship came about. I was still an Assistant Professor at the time it was finalized, and now I’m an Associate Professor. So now it’s the Leslye M. Heisler Associate Professorship, and hopefully I can carry it forward and take it to when I become a full professor.

NABHAN: How did we progress from where we were 20 years ago to where we are right now in the fight against lung cancer?

AGGARWAL: I think the tipping point was the discovery of the actionable EGFR mutation. I think that really accelerated the definition of subtyping of NSCLC subtypes. I think just that whole movement of how you must test for EGFR mutation, and then shortly followed by ALK translocations, made a difference. The entry of targeted therapy made a huge difference in the lives of our patients. Using drugs such as crizotinib or erlotinib at the time, we could keep patients off chemotherapy and with a median progression free survival (PFS) of nine and 11 months, which was unheard of in the lung cancer world at that time. Fast forward to 2020, it’s mindboggling that we now have seven actionable targets in the front line setting with more coming in the second line. In 2021, we might expand it to 10 actionable targets. The second thing is the huge movement behind immunotherapy. If I recall correctly, at the oncology meetings in 2014, there was barely anything related to immunotherapy. In 2015, maybe we were seeing a few phase-I’s. Then 2016 comes around and the oncology meetings were completely different. I remember sitting in even a head and neck session in 2016 and at least half of the oral abstracts were all related to pembrolizumab and nivolumab. How much change two years made was remarkable. How do we take it beyond where we are in immunotherapy? I feel like we’ve stalled a little bit, at least in the lung cancer space. We’re really looking for that powerful second line combination that can help us out — but look at where we were and where we are. It’s super exciting.

NABHAN: Where will we be five years from now in managing lung cancer in the early stages and advanced stages of the disease?

AGGARWAL: This answer may be biased because this is my area of research. I think in the future everyone will be getting liquid biopsy, be it early stage or late stage. I think in five years we will have refined the technology to a point where we’re not just using it for initial therapy selection but we’re also using it for things like monitoring of response. We already have some emerging data that you can use ctDNA for monitoring response for targeted therapies, but there’s also emerging data that we could potentially use this as a non-invasive biomarker to assess for response to either escalate or deescalate therapy when it comes to immunotherapy. I do think we’ll be using it in the future in some way or form in conjunction with or in place of radiologic assessment of disease. I think that’s one thing that will happen in the metastatic setting. In the early stage setting, I think we’ll be using [I say loosely] liquid biopsy, but it may be other technologies that have us look at identification of patients with higher risk disease within that pool of patients that have stage I-III disease. I think we’re going to be looking at better biomarkers to drive therapy in early stage disease. I think combination biomarkers are coming where we can use three or four different biomarkers together to perhaps give us a score that drives therapy. In fact, something that Caris is developing is to precisely tell us what we should be doing. We have such a wealth of information that it’s really incumbent upon us to use it.

NABHAN: What do you like to do for fun?           

AGGARWAL: I love to travel. I was in Iceland last year during the summer and then Barcelona. We often joke with our children that they’ve traveled to more countries than their collective ages combined, and they still tease us by reminding us that they have never been to Florida. My last couple of family vacations before the pandemic were in Grand Cayman in December 2019 and then Arizona in February 2020.

 

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Dr. Charu Aggarwal

Leslye M. Heisler Associate Professor for Lung Cancer Excellence
Division of Hematology-Oncology

University of Pennsylvania