Maurie Markman, MDDISCL OSURES
October 04, 2023
I’m Dr Maurie Markman from City of Hope, and I would like to discuss a fascinating, long-term, follow-up study of a trial that was completed many years ago but addresses a very important, clinically related matter.
The trial I am referring to, published in the Journal of Clinical Oncology, is A Phase IB/II Study of Lenvatinib and Pembrolizumab in Advanced Endometrial Carcinoma (Study 111/KEYNOTE-146): Long-Term Efficacy and Safety Update.
There is a very interesting series of trials that have been conducted in endometrial cancer. Even discussing the topic of definitive, interesting, or innovative trials in endometrial cancer feels somewhat strange for someone like me, who has been involved in the area of clinical research and management of gynecologic cancers for almost 40 years.
We always talk about ovarian cancer trials. The idea that you would study drugs in endometrial cancer in a primary setting without having already shown value in ovarian cancer would have been unheard of 10, 15, or 20 years ago. But we are now making major strides in endometrial cancer. In fact, the study I’m referring to, in its prior publication demonstrated that the combination of lenvatinib and pembrolizumab in a patient population that had already received chemotherapy was quite efficacious.
The study I’m referring to is a single-arm phase 1B and 2 study. Subsequent to the conduct of that study, which had been published previously, there was a phase 3 randomized trial conducted that demonstrated that this particular combination, compared with a standard of care, the control arm, improved clinical outcomes.
You might ask, “Well, if we already have a phase 3 trial looking at this combination that shows superiority, why go back and look at the prior publication of the single-arm trial?” But that’s the point I want to make.
The value of looking at the long-term outcomes of the previous study is that it gives you longer-term information even compared with what you can see in the latest randomized trial, which of course started after the earlier trial I’m referring to here.
Going back and looking at the follow-up results in this earlier trial, looking at what happens to the patients [allows you to ask important questions]. How long did the responses last and were there side effects that occurred later that are relevant to patients you’re potentially treating today? That’s what this study did.
The earlier trial I’m referring to included approximately 100 patients with a median follow-up now of more than 3 years. In fact, the objective response rate was approximately 40%, which is very similar to what was seen in the randomized trial.
The critical point to be made here is that not only did we see a high objective response rate of 40% in a patient population that already received one or even two prior chemotherapy regimens, but the median duration of response — this is second-line therapy of advanced or metastatic endometrial cancer — was essentially 2 years.
Think about that for a moment. Using a second-line therapy for patients who have already progressed on chemotherapy in endometrial cancer, 40% of these patients achieved an objective response and the median duration of those objective responses was 2 years.
Obviously, there is a major impact of this therapy, a very important outcome, and this is a very important paper in the area of endometrial cancer management and in the whole domain of gynecologic cancer therapy.
I encourage you to read the paper if you have not already. I thank you for your attention.
Maurie Markman, MD, is a professor in the Department of Medical Oncology and Therapeutics Research at City of Hope in Duarte, California, and the president of Medicine & Science at City of Hope Atlanta, Chicago, and Phoenix. He has more than 20 years of experience in cancer treatment and gynecologic oncology research.
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