Doctor David O’Malley, MD, professor and Director of Gynecological Oncology at The Ohio State University Wexner Medical Center and the James Comprehensive Cancer Center, talks about how a drug called Keytruda helps women with endometrial cancer.
Interview conducted by Ivanhoe Broadcast News in April 2022.
What is endometrial cancer and how does it impact women?
DR O’MALLEY: Endometrial cancer is a cancer of the lining of the uterus. And that is when we look at the endometrium or uterine cancer, we use those terms interchangeably. That cancer undergoing malignant transformation based on several factors, de novo, hormonal, lots of different reasons. Most uterine cancers, luckily, are confined to the uterus. But approximately, about a quarter of them will metastasize either locally to the tubes and ovaries or regionally to the lymph nodes. And they can metastasize or leave and go anywhere in the body, even into the abdominal cavity.
What’s the first line treatment for uterine cancer?
DR O’MALLEY: First line treatment for uterine cancer is surgery. Once we identify those at the highest risk, for example, those who have metastasized, we then tailor the treatment – chemotherapy, radiation, sometimes both.
When you have a cancer that is aggressive and that comes back, what are the options? What options have women had?
DR O’MALLEY: In the past, the options for recurrent uterine cancer were fairly limited. I would tell patients, if your cancer comes back, it ultimately will win. It ultimately will kill you. That’s what I used to say. The first line treatments for recurrent cancer were usually chemotherapy. There were very limited options. There still are. Hormonal therapy – and that was about it. Potentially radiation. Now we have the ability to treat patients with immune therapy.
And that’s something that’s fairly new, isn’t it?
DR O’MALLEY: It is. The treatment of recurrent uterine cancer is very new. I was honored to present Keynote 158, which was a study across lots of different tumors. But we looked at two cohorts that were endometrial cancer and we identified about 80 patients that have certain abnormalities in their tumor. So, changes in their tumor, which are called mismatch repair deficient or MSI High. What we know about patients with those types of tumors, their tumors seem to respond much better to immune therapy.
When you have women with these tumors who respond to immunotherapy, what is available? What did you and your colleagues test?
DR O’MALLEY: Well, pembrolizumab, or Pembro, is a PD-1 inhibitor. What it does is removes the blockers that the cancer has, which helps it evade or avoid the body’s immune system. So, the cancer is very smart. The immune cells get there, but the immune cells can’t do their job. And so, what this drug does is it removes those blockers, allowing the body’s own immune system to then kill the cancer cells.
How effective was this on the women with this abnormality?
DR O’MALLEY: We saw results, which were unprecedented in this report. We saw nearly one half of patients met the criteria for partial response. Nearly 50 percent of those met the criteria for a complete response. But even if patients did not meet the criteria for response. Many of them still benefited from the therapy by keeping the disease stable.
Even though this was a phase two trial, the results were so good that it’s now an approved. Can you talk a little about that?
DR O’MALLEY: So, Pembro was originally approved – the first approval for an agnostic – meaning across all tumor types that had these tumors – changes in their tumors MSA high and then MMR deficient. What our report did was led to the approval just for endometrial cancer in those patients with tumors with these changes. The reason is not only that nearly 50 percent response rate, but if you responded, you had more than a two-thirds chance of that response lasting more than two years. In the past, typically the responses were three to four months, and if we had a response of six months, we celebrated. Two-thirds of patients responded more than two years.
Why is it so important for patients to be able to buy that long length of time for patients?
DR O’MALLEY: The responses that we saw not only had patients living longer, but the survival of recurrent endometrial cancer not that long ago was also less than about 18 months. And now in this trial, we had 60 percent of people alive at four years or more. We’ve now allowed patients to have the opportunity to see their kids grow, their grandkids, and graduations. I don’t know how to counsel patients. In the past, I said if the cancer recurred, it would kill you. I had patients who have been cured of recurrent uterine cancer because of the treatment with immune therapy. I didn’t think I would see that in my lifetime – cured of recurrent cancer based on these therapies.
As a result, are some of your colleagues working at the drug Pembro for earlier stage uterine cancer?
DR O’MALLEY: There are multiple ongoing trials looking at utilizing Pembro as well as other immune therapies earlier on in the lines of therapy. So, this report was patients who had previously been treated with our standard chemotherapy of carboplatin paclitaxel as well as other therapies. We now are looking at treating patients with those two agents – the chemotherapy plus Pembro, comparing it if we don’t use Pembro. And we’re also starting in patients who are a higher risk recurrence, even with localized disease. So, you may have a patient whose cancer is confined to the uterus but has a 25 percent-plus chance of recurrence. If the cancer comes back, controlling it is extremely difficult. So, now what we’re doing is studying if we gave patients immune therapy or Pembro can we cure more people? Can we avoid recurrence? When these trials are completed, I imagine any patient who has these changes in their tumor, MSA-high, will have the opportunity to use Pembro in their treatment moving forward.
What other cancers have doctors prescribed Pembro for?
DR O’MALLEY: It would be melanoma, colorectal, non-small cell lung.
When did the trial wrap up?
DR O’MALLEY: The average follow up was three and a half years. That’s one reason why we have such good data.
Is there anything else that you would want people to know?
DR O’MALLEY: Precision medicine is here. All patients should have their tumor tested. One of the tests we need to look at is MSI high or deficient MMR. It’s very important that patients, particularly if the disease has recurred, their tissue is tested for these types of abnormalities. One could argue that anybody diagnosed with uterine cancer should have these tests performed on their tissue to see if they’re a candidate for these clinical trials. And hopefully in the future, we’ll know much better of who we should be treating with immune therapies like Pembro.
END OF INTERVIEW
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