Twenty five years ago, cancer was almost a different disease. Despite the so-called War on Cancer, declared in 1971 by President Richard Nixon, treatments had mostly remained the same blunt instruments — brutal chemotherapy, surgery and radiation. It seemed as if cancer had won the war.
Now, cancer medicine is in a new place. An increasing array of treatments precisely target the cancer itself. And for some cancers, researchers have learned to direct the immune system to kill the malignant cells. Cures are possible for some cancers that had seemed incurable. Many patients can live longer and better lives than ever seemed possible. Cancer death rates have been plunging, and researchers attribute most of that to improved treatments.
Overseeing this change at the Food and Drug Administration has been Dr. Richard Pazdur, currently the director of the Oncology Center of Excellence. Trained as an oncologist, he leads the agency and its cancer specialists in determining how cancer drugs are tested and approved.
Through 25 years at the agency in a variety of roles, he has been present from the start of the new era and has seen firsthand how scientific discoveries completely changed the prospects for many cancer patients. In two edited and condensed conversations, he discussed what he has seen, and what he hopes for.
What was it like to be a cancer doctor when you first began, and what has changed?
When I started in medical oncology in 1979, we had less than 40 oncology drugs for all cancers. I came to the F.D.A. in 1999, thinking that most drug development would be done by the National Cancer Institute. I thought industry would have very little interest because most drugs were short course with excessive toxicity and many patients had a poor prognosis.
I couldn’t have been more wrong. For many patients, things have changed dramatically. From 1999 until the present, we approved 201 cancer drugs. When I came to the F.D.A. there were about 10 medical oncologists at the agency. Now there are 100.
Was there a moment when you realized a new era had begun?
It was a gradual thing. I wish I could say I had an “a-ha” moment.
I remember though, one of our first approvals of a PD-1 drug (a drug that unleashes the immune system to fight cancer). A division director sent me an email with a survival curve for patients in a study. It was a Friday afternoon. I saw it and I nearly fell off my seat. It was such a positive study for these patients with squamous cell lung cancer. They lived an average of six months with standard chemotherapy. With the new drug they lived 9.2 months.
I called the division director and said, “What are we going to do to expedite this?”
We had to get a submission from the drug company and that can take several months. Sometimes it takes six months and sometimes up to a year because of the voluminous amount of material that must be provided.
We got the submission in a couple of months. Nivolumab was approved in March of 2015.
It was a major therapeutic advance. These were people who heretofore had few therapeutic options.
You started a program called Project Patient Voice. What is that about?
Patients report their symptoms during clinical trials by filling out questionnaires, but their reports are rarely included in the drugs’ labels. Instead, what is included is reports from clinicians on a drug’s side effects.
We have heard from multiple patients telling us that they want to know what to expect and how they will feel when they take a drug. But these are not easy endpoints to examine. Patient reports are subjective — we generally don’t have placebo-controlled trials in oncology so there is a potential for bias.
But patient reports are very important to us. With Project Patient Voice, patients and their oncologists can go to the website together and see how often patients reported different side effects, how severe they were and when they occurred.
Your wife died of ovarian cancer. Did her experience affect the way you view reports of drug side effects?
How could it not? It did not change the agency’s viewpoint but it made me reflect and concentrate more heavily at how we look at drug safety.
She had a great deal of toxicities, so I fully understand the side effects of drugs. We at the F.D.A. see toxicities as data, as data points. Even the physicians see them that way. And sometimes patients minimize their symptoms when they talk to their physicians.
When my wife went to see her doctor he would ask, “How are you doing on this therapy?” She would say “Fine.” But I knew what was happening.
It is one thing to see a patient in clinic or to see the data on a patient versus being with a patient. When I was leaving in the morning, my wife would say she was fatigued. She would still be on the couch at 4 in the afternoon. She hadn’t moved.
You also started Project Optimus. What is it, and why did you start it?
We were concerned that cancer drug doses could be too high, leading to unnecessary side effects. In other areas of medicine, it is routine to find the lowest dose that is effective. But oncology has used the maximum tolerated dose and it has been very hard to move away from that. It started in the 1950s and 1960s when oncology drugs were primarily developed using metabolic poisons. The idea was that you wanted to get as much of these poisons to the cancers as possible. People just accepted that the maximum tolerated dose was just the cost of using these therapies.
Now we need to step back and take a look at doses. Not having the right dose is literally building a house on quicksand. It’s just bad drug development. Project Optimus is an initiative to work with companies to find the lowest effective dose before starting clinical trials that could lead to drug approval.
Have you regretted anything during your work at the F.D.A.?
Regrets are not in my DNA. Long ago I realized I am not a fortune teller. I make decisions with the data at hand and acknowledge that these decisions can change if and when new data emerge. That said, my regret? I won’t be here in 2049, my presumed 50th F.D.A. anniversary.
I would love to see what oncology looks like given the rapid changes in the past 25 years. Hang on tight. The velocity of innovation will only increase.
