Bradley J. Monk, MD, on Cervical Cancer: Findings on Pembrolizumab Plus Chemotherapy
2023 ASCO Annual Meeting
Bradley J. Monk, MD, of the University of Arizona, Phoenix, and Creighton University, discusses phase III findings from the KEYNOTE-826 study of overall survival results in patients with persistent, recurrent, or metastatic cervical cancer. Study participants received first-line treatment of pembrolizumab plus chemotherapy, with or without bevacizumab, which reduced the risk of death by up to 40% in three different subsets of patients (Abstract 5500).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
I'd like to share with you my perspective about the treatment of women with recurrent metastatic or persistent cervical cancer. This is a group of patients that we call as the first line treatment. Now, this is a very serious problem. This is the number four cause of cancer death worldwide, and in this country, it causes more than 4,000 deaths. So historically, the treatment has been doublet chemotherapy, platinum, and taxane. And then in 2014, we added bevacizumab to it with a small improvement in overall survival of only three to four months. And here we've sat, since 2014, chemotherapy with or without bevacizumab.
Now, immune therapy is everywhere. It got a very limited conditional approval in the second line in 2018, but we wanted to move it to the first line with chemotherapy, with or without bevacizumab. So on behalf of the 151 sites in 19 countries, I'd like to share with you the results of Keynote 826, which randomized 617 patients one-to-one, chemotherapy with or without bevacizumab, to pembrolizumab or placebo. And that trial led to FDA approval in October 2021, but it was an interim result. It was very preliminary, and now I'd like to share with you the final result.
And the final result is that when pembrolizumab is added to chemotherapy versus placebo, there was a 40% improvement in overall survival. What does that mean? That means they live a year longer. A terminal disease that now, average age of 50, live a year longer. And we might even be curing some patients. It's too early to tell. But this is a two-year treatment, six doses of chemotherapy, and then two years of total immune therapy. And then at three years, a third of the patients are now without progression and a year without treatment. There is a plateau, 30% of the patients or so.
So this is a major step forward. This confirms two things. Number one, that the preliminary result is real with a year improvement overall survival. And second, that pembrolizumab is best used in the front line rather than in the second line. And these are patients who have PD-L1 high expressing tumors according to the 22C3 antibody CPS greater than equal to one, which is 89% of the patients. So this is an opportunity for almost all patients with first line cervical cancer to add pembrolizumab to chemotherapy with or without bevacizumab at the discretion of their provider.
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris-Saclay, discuss findings from the TALAPRO-2 study, which showed that talazoparib plus enzalutamide improved radiographic progression–free survival over standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer and HRR gene alterations. This regimen also delayed the time to deterioration in global health status and quality of life (Abstract 5004).
LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston Methodist Hospital, discusses study findings showing that CD5 chimeric antigen receptor (CAR) T cells may induce clinical responses in heavily treated patients with relapsed or refractory T-cell acute lymphoblastic leukemia. Manufacturing CD5 CAR T cells with tyrosine kinase inhibitors seemed to improve their potency and antitumor activity (Abstract 7002).
Smitha Krishnamurthi, MD, of the Cleveland Clinic, and Deb Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, discuss phase III findings from the PROSPECT trial, which showed FOLFOX chemotherapy with selective use of radiation therapy and sensitizing fluoropyrimidine (5FUCRT) is noninferior to 5FUCRT for the neoadjuvant treatment of patients with locally advanced rectal cancer, prior to low anterior resection with total mesorectal excision (Abstract LBA2).
Ajay K. Nooka, MBBS, of Winship Cancer Center of Emory University, discusses findings from a pooled analysis of MagnetisMM studies. The data showed that, in patients with relapsed or refractory multiple myeloma who have not yet been treated with B-cell maturation antigen–directed therapies, elranatamab was efficacious and well tolerated.
Thomas E. Hutson, DO, PharmD, of Texas Oncology, discusses the 4-year follow-up results from the CLEAR study for patients with advanced renal cell carcinoma (RCC). The data showed that lenvatinib plus pembrolizumab continues to demonstrate clinically meaningful benefit vs sunitinib in overall and progression-free survival, as well as in overall and complete response rates, in first-line treatment (Abstract 4502).