Making Cancer Drugs Available For A Wider Pool Of Patients

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Cancer treatments have become more and more effective and specific. But for patients with stage IV cancer, the options can be limited while new drugs are coming to the market. The FDA only approves them for a specific subset or stage of cancer, sometimes even for a specific age group.

And researchers are looking to expand the pool of patients that can get these new treatments. And my next guest is one of those researchers. Dr. Sara Hurvitz is an associate professor and director of the Breast Cancer Research Program at UCLA. She joins me from Los Angeles. Welcome to Science Friday.

SARA HURVITZ: Thank you.

IRA FLATOW: You’re researching a breast-cancer drug. Tell us about the drug. What is the kind of cancer, breast cancer, that it treats?

SARA HURVITZ: So the drug itself is called ribociclib. And it belongs to a class of medications called cyclin-dependent kinase 4/6 inhibitors. That’s a mouthful. So we call them CDK 4/6 inhibitors. And the type of cancer that this treats, the type that we studied, was hormone receptor-positive metastatic breast cancer.

There are three different CDK 4/6 inhibitors that are available and were already FDA approved in the past few years for the treatment of this type of breast cancer. But the one that we are looking at in this particular clinical trial was ribociclib.

And we were specifically addressing whether or not adding this drug to a standard anti-estrogen therapy for this type of breast cancer would improve outcomes for women who are young, who had not yet gone through menopause. This is a patient population that is not typically studied as a whole, specifically, in a study. Sometimes with young women will be allowed on a trial, but our trial was specifically for them.

IRA FLATOW: And you got unexpected results, unexpected positive results, with this.

SARA HURVITZ: Yes. So we already published last year, similar to other studies that have been done with other CDK 4/6 inhibitors, we showed that when you add this therapy to standard endocrine therapy, it substantially prolongs the amount of time a woman can live with her breast cancer without it getting worse. Our particular trial, it was greater than a 10-month improvement in what we call “progression-free survival,” or the length of time a woman can have control of her disease before the resistance develops.

What we presented this past week and has received a lot of attention is the fact that we were able to demonstrate that women who receive this medication lived longer, period, not just lived longer with the disease controlled, but their survival was better. So if you look at one landmark point at 42 months after the women had been on this study, 46% of the patients who received anti-estrogen therapy alone were still alive. But if you looked at the patients who received this drug called ribociclib, 70% were still alive. So that’s a–

IRA FLATOW: Wow.

SARA HURVITZ: –meaningful difference.

IRA FLATOW: Yeah. And these were younger women, right, whom you gave it to?

SARA HURVITZ: Yeah. They were all under the age of 59. There was over 670 patients enrolled in this study. And they were all pre- or perimenopausal, so their ovaries hadn’t stopped functioning yet. They hadn’t gone into menopause yet.

IRA FLATOW: And is it possible then to find even another class of women with breast cancer who might benefit from this next year?

SARA HURVITZ: Absolutely. And if you have time for a little story–

IRA FLATOW: Sure.

SARA HURVITZ: –I can tell you that this class of medications, actually, it’s very gratifying to be involved at this point in the story when survival has been demonstrated because I’m part of the laboratory at UCLA that is run and has been funded by Dr. Dennis Slamon. You may know that name because Slamon, in the 1980s, discovered that HER2, a protein that’s expressed on cancer cells, is overexpressed in 20% to 25% of all breast cancers. And it’s a very poor-prognosis-associated cancer. He was kind of the first to say that there are breast cancer subtypes. And his sentinel findings led to the development of targeted therapy against HER2, known widely as Herceptin.

IRA FLATOW: Mhm.

SARA HURVITZ: And that story led to a lot of philanthropic funding and government funding. And he pooled all of that funding to develop a large laboratory which uniquely allows all of his colleagues in cancer research in our division, we all share the resources from the fruits of his labor. And he developed this large cancer cell-line panel, 600 different cancer cell lines, so that we could study new drugs and see how they work. You know, when people say, why isn’t there a cure for cancer? It’s because cancer is not one disease. It’s like, why isn’t there a cure for infection? There are many, many different subtypes.

So he had 50 or so different breast cancer cell lines. And we received a drug in the laboratory around 2008, 2007 from a large pharmaceutical company that blocks this pathway, this cyclin-dependent kinase pathway, which tells the cancer cell that it can divide. It can go into cell division. And the company that handed it over said, look, try it in your cell-line panel. Treat your cell lines with it, and see if you get a signal of the type of cancer where this will work.

And so he had a very smart PhD postdoc in his lab by the name of Dylan Conklin who had tweaked the way that we run this experiment in the laboratory. And he was able to demonstrate and with his team, led by Rich Finn, that hormone receptor-positive breast cancer, the most common form of breast cancer, is exquisitely sensitive to this inhibitor. And so that led to a phase I study. I was relatively new.

IRA FLATOW: I have to interrupt your story.

SARA HURVITZ: Mhm.

IRA FLATOW: I know it’s an interesting story. I want to bring on another guest–

SARA HURVITZ: [INAUDIBLE]

IRA FLATOW: –a researcher who is looking to expand uses of the cancer drugs. And we’ll talk a little bit more about yours. I want to bring in Dr. Neeraj Agarwal, who joins me from Salt Lake City. He’s a professor of medicine and director of a Genitourinary Oncology Program for the Huntsman Cancer Institute at the University of Utah. Welcome to Science Friday, Dr. Agarwal.

NEERAJ AGARWAL: Thank you very much.

IRA FLATOW: You’re looking at a new drug for stage IV prostate cancer. Tell us about the drug, and what type of cancer cells does it treat?

NEERAJ AGARWAL: Sure. So, as we know, prostate cancer, just taking a step back, prostate cancer is the most common, one of the most common, cancers in American men, just after skin cancer. So if you take out skin cancers, prostate cancer is the most common cancer in American men and the second-most common cause of cancer-related deaths in American men after lung cancer. So this is a disease which impacts hundreds of thousands of men on a yearly basis.

So this clinical study, which I had the privilege of being on the steering committee and steering the whole trial at the global level, included a new drug, apalutamide, which is a novel androgen-receptor inhibitor, which basically means it targets a protein known as androgen receptor, which drives the cancer cells, prostate cancer cells.

So until now, until like from 1942 when it was discovered that testosterone is the fuel for prostate cancer, the strategies to block testosterone production in the gonads became the mainstay of treatment. And that did not change until 2013 when addition of chemotherapy up front or the drug abiraterone with steriod was shown to improve survival.

So fast-forward moving to 2019. We were using chemotherapy with docetaxel or this drug abiraterone, which requires concomitant steroids, for many years. Those were the two standards for these men. Now, in 2019, we published this study in The New England Journal of Medicine just last week. And this is about a large phase III trial, more than 1,000 men with advanced or metastatic prostate cancer, newly diagnosed. And they were randomized to standard androgen deprivation therapy versus androgen deprivation therapy what this new drug, apalutamide.

And what we saw was really remarkable. Both dual-primary endpoint of this trial, which were overall survival and progression-free survival, which basically means how long the disease was contained by this drug and was not allowed to progress, so progression-free survival, both were remarkably and statistically significantly improved by adding apalutamide. There was a 33% reduction in the risk of death and 52% reduction in risk of progression of disease.

So given, based on these findings– and of course, I would like to add something really quick. Whenever we talk about these newer drugs, we always worry about side effects. Yes, we are getting two extra years, three extra years for these men. But at what cost? So the remarkable part of this study was that the quality of life in men who were receiving apalutamide was preserved and maintained while they were under treatment, despite getting many months to years with survival benefit.

So overall, if you look at grade 3, 4 side effects, which we call as clinically significant side effects, were very similar in both arms, 42% versus 40%. So yes, this drug improves survival outcomes, and doesn’t increase side effects, and maintain quality of life. So that’s what I wanted to summarize.

IRA FLATOW: So do you think this will become a standard of practice of using this new drug?

NEERAJ AGARWAL: That’s a great question. So I once said, this will be the only standard practice. A similar drug, enzalutamide, was also shown to improve survival or the overall survival in this meeting. At the same time, and our paper was published and presented. So I think these two drugs, which belong to this novel class of drugs known as direct androgen receptor inhibitor, I think they will become the mainstay of treatment in these patients.

Most of my patients– I have very few patients who are very enthusiastic about getting chemotherapy or steroids for long durations. So I think this is a very welcome change or very welcome option for those patients.

IRA FLATOW: Dr. Hurvitz, do you think there are other drug combinations that are out there, and I mean in different permutations, that have yet to be tried that might be successful in treating breast cancer?

SARA HURVITZ: Yes. Absolutely. And I’m struck by Dr. Agarwal’s results. They’re very similar to the ones I’ve been discussing. And I think it’s fascinating because both of these studies were dealing with a hormonally driven, highly-common cancer. And both studies, I think, showed that when you add a new agent to a hormonally directed therapy, you get great outcomes.

The pipeline for new targeted therapies for many cancers, not just breast cancer, seems like it’s exploding at this meeting. I think many of us meet with one another, academic centers, and industry partners discussing some very exciting therapies that are on the forefront and will hopefully show promising results like the ones that we’re presenting here today.

IRA FLATOW: Dr. Agarwal, do you agree there are other combinations and other benefits to looking at drugs that are available all the time and then finding new combinations for them?

NEERAJ AGARWAL: Yeah, absolutely. I think this is just a start for us. All these men, it doesn’t matter how much we have improved survival, this remains a fatal disease down the line. And there’s so much more needs to be done. And I think anything we can do to make the drug development faster and availability to our patients, make it easier for these drugs to become available to our patients, I think anything we can do in that direction, we should do it.

IRA FLATOW: You seem to be saying that the side effects, or the lack of them, may actually makes them more tolerable for these patients, and that’s why they’re willing to take them.

NEERAJ AGARWAL: Yes, all these new drugs, I tell my patients they usually have less than 10% side effects what we used to see with traditional chemotherapies.

IRA FLATOW: Hm. I’m Ira Flatow. This is Science Friday from WNYC Studios. Dr. Hurvitz, do you find that true with your new medicines?

SARA HURVITZ: Yeah. Sometimes the new therapies that we look at have a great effect, a great benefit. But the side effects are something that we really have to manage and deal with. So there are some therapies that don’t show a benefit in terms of quality of life parameters.

As a note, most of our clinical trials now require us to survey patients throughout the study to ensure that their quality of life is preserved. It’s now a mandate. The ribociclib therapy, similar to what Dr. Agarwal is talking about, is also incredibly well tolerated. Patients feel well on this drug and are generally not affected. They’re able to lead productive, high-quality life.

IRA FLATOW: If these are drugs that are not normally prescribed for those types of cancers, will medical insurance or Medicare pay for these drugs?

SARA HURVITZ: Yes. So it’s a great question. The cost of these new therapies is certainly something to consider. And the therapy I’m discussing is already FDA approved. So this is just sort of cementing in stone, if you will, that the benefits are quite important and significant.

But on a global perspective, in speaking with colleagues overseas, drugs like this are approved. But that doesn’t mean that they’ll be funded. Many health care systems will require that overall survival be demonstrated before funding will occur. So my hope is that now that survival benefit has been demonstrated that the access to this lifesaving medication will be broadened globally.

And I’d also like to point out that, as you mentioned, this drug is FDA approved for metastatic breast cancer. But it’s now being evaluated in the curative setting. There are ongoing studies to evaluate whether or not we can reduce the risk of recurrence for early-stage disease.

IRA FLATOW: Is that true also of your drug combination, Dr. Agarwal? Will it be reimbursed by Medicare, or drug companies– or insurance companies?

NEERAJ AGARWAL: Yeah. So we are waiting for FDA approval of this drug, apalutamide. And we are really hoping that FDA will approve the apalutamide for patients with metastatic, castration-sensitive, or advanced prostate cancer very soon.

IRA FLATOW: And where can people learn more about your drug and, also, your drug too, Dr. Hurvitz?

SARA HURVITZ: Yes, so online, there are a number of resources online and available at just googling the ribociclib, or cyclin-dependent kinase 4/6 inhibitor is a good resource. There are a number of other online resources where you can find out information.

IRA FLATOW: Dr. Agarwal?

NEERAJ AGARWAL: I agree. It’s so much easier to find information now compared to what we used to have like 10 years ago, even. So apalutamide is the name. And Googling with apalutamide I think will get a lot of answers. But there are a lot of good places to look for these drugs and more information. I think I would start with Prostate Cancer Foundation, American Cancer Society, and so on.

IRA FLATOW: All right, we’ve run out of time. I want to thank you both for taking time to be with us today, Dr. Sarah Hurvitz, associate professor and director of the Breast Cancer Research Program at UCLA. Dr. Neeraj Agarwal is professor of medicine and director of the Genitourinary Oncology Program for the Huntsman Cancer Institute, the University of Utah. Dr. Hurvitz, Dr. Agarwal, thank you for being with us both today.

SARA HURVITZ: Thank you.