Immunotherapy Perspective From a PD-1 Pioneer

Anita T. Shaffer and Gina Columbus
Published: Tuesday, Jul 05, 2016
Suzanne L. Topalian, MD

Suzanne L. Topalian, MD

It was 4 years ago that Suzanne L. Topalian, MD, stepped into the spotlight at the ASCO Annual Meeting to report early efficacy for a novel antibody aimed at what was then the little known PD-1 immune checkpoint.

Since then, therapies aimed at the PD-1/PD-L1 pathway have mushroomed, with three approved agents indicated in a total of five tumor types and continuing development suggesting that more new drugs are on the way.

Although the rapid expansion of these therapies sounds like an overnight success, Topalain has been studying ways to harness the human system to fight cancer for more than 30 years. In 140 peer-reviewed articles, she has explored cancer vaccines, tumor-infiltrating lymphocytes, and the immune checkpoint CTLA-4 in addition to the PD-1/PD-L1 pathway.

A graduate of Tufts University School of Medicine, Topalian spent 21 years in the Surgery Branch of the National Cancer Institute. In 2006, she was named to lead the Melanoma Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine in Baltimore.

In June, Topalian was recognized for her groundbreaking work in immunotherapy along with Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center. The two clinician-scientists were named as the joint winners of the 2016 Taubman Prize for Excellence in Translational Medicine. They will share the $100,000 prize, which is awarded by the University of Michigan’s A. Alfred Taubman Medical Research Institute and will be presented in October.

OncLive sat down with Topalian during the 2016 ASCO Annual Meeting to discuss progress in PD-1/PD-L1 immunotherapies and the prospects for developing biomarkers to better identify patients who would benefit from the new agents.

OncLive: When you presented the first research into PD-1 inhibitors at ASCO 4 years ago, you indicated that this approach could potentially be applied in multiple tumor types. Are you surprised that anti-PD-1/PD-L1 inhibitors have become such a big focus and success, or is this what you had envisioned?

Topalian: Four years ago, of course, we were just giving the first report that one of the anti-PD-1 drugs was active in three different cancer types. So that was very early but very promising evidence. At that time, I think the most surprising aspect of it was the responsiveness of non–small cell lung cancer, which had not been responsive to other kinds of immunotherapy before that report. But the responsiveness of lung cancer suggested that maybe additional types of cancer could be responsive as well.

I think what we’re seeing here at the meeting in 2016 are reports on many different kinds of cancers now that are responsive to several different anti-PD-1 or anti-PD-L1 drugs. Although we hoped that this might be the scenario, I think this has really exceeded our expectations.

Some observers have suggested that immunotherapy, particularly the PD-1/PD-L1 pathway agents, are the new chemotherapy in the sense that they will become a backbone of cancer treatment, even replacing chemotherapy in some settings. Would you agree with those observations?

I hope that they will in some cases replace chemotherapy. If the meaning is that it will become as commonly used as chemotherapy, we hope that will happen.

But they’re not the new chemotherapy in the sense that in many cases they are not as toxic as chemotherapy. The quality of life for patients who are getting PD-1 inhibitors is actually better and this has been shown in some of the randomized trials that have been published comparing these agents with chemotherapy. One notable example is in lung cancer comparing second-line chemotherapy to an anti-PD-1 inhibitor.1 Hopefully, this is a better way to use the patient’s own immune system to treat cancer, which will not have all the toxicities that we have experienced with standard chemotherapy.

Do you see PD-1/PD-L1 inhibitors moving into first-line therapy even when patients have a mutation that can be targeted?

Yes, I think we’re already there, at least in melanoma where two different drugs have been approved now in the first-line setting, two anti-PD-1 drugs.

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