Danny Rischin, MD, MBBS, FRACP
The PD-1 inhibitor cemiplimab (Libtayo) as monotherapy and in combination with hypofractionated radiotherapy demonstrated antitumor activity with a tolerable safety profile in patients with metastatic or recurrent cervical cancer, according to data presented at the 2018 ESMO Congress.
In the open-label, international, phase I GOG 3016/ENGOT-cx 9 study (NCT03257267), results showed that the investigator-assessed overall response rate (ORR) was 10% in the two 10-patient cohorts treated with the immunotherapy agent, and the disease control rate in both cohorts were 20%.
Patients with recurrent or metastatic cervical cancer resistant to platinum and taxane doublet chemotherapy received cemiplimab at 3 mg/kg every 2 weeks for up to 48 weeks. Patients randomized to the combination also received hypofractionated radiotherapy at 3 times per week, starting 1 week after the first dose of cemiplimab.
In the cemiplimab monotherapy cohort, the median time to response was 1.84 months compared with 1.77 months when combined with radiotherapy.
The most common treatment-related adverse events (AE) reported were diarrhea at 40% and 30% in the single-agent and combination arms, respectively. Fatigue, hypokalemia, and pain in extremity were also reported in the monotherapy cohort (30%), while urinary tract infection was reported in the combination cohort, all of which were grade 1/2. There was one case each of grade 3 diarrhea, fatigue, hypokalemia, and anemia.
An ongoing, international phase III trial is looking at single-agent cemiplimab versus chemotherapy in patients with recurrent or metastatic platinum-refractory cervical cancer (NCT03257267).
The PD-1 inhibitor is currently FDA approved for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who are not candidates for curative surgery or radiation.
In an interview with OncLive
, lead study author Danny Rischin, MD, director of the Division of Cancer Medicine and head of the Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, discussed the potential of cemiplimab in patients with cervical cancer.
OncLive: Please provide an overview of this cervical cancer study.
Rischin: This is a trial of cemiplimab, a PD-1 monoclonal antibody. There were multiple expansion cohorts, and there were 2 cohorts of patients with advanced or recurrent cervical cancer. One of those cohorts was cemiplimab monotherapy, and the other was cemiplimab with radiotherapy given 3 times in the same week of the treatment program. There was 1 PR in each cohort. Some patients had what we call durable disease control—at least 3 months without progression.
What was the rationale for testing cemiplimab in this patient population?
In the phase I study, there were multiple cohorts. The [data with] cutaneous squamous cell carcinoma came out of the same study. We saw very promising data and remarkable activity, which led to the subsequent studies and FDA approval of the drug in that space. In cervical cancer, cemiplimab has modest activity, similar to what has been seen with other checkpoint inhibitors. It has led to the phase III study of looking at this in the second-line setting against chemotherapy, which we know has not been very effective.
What are the next steps following these results?
There is a phase III study underway for patients with metastatic or recurrent disease who have progressed after first-line chemotherapy. They are usually treated with platinum-based regimens and often with bevacizumab (Avastin). Once they progress on that, there are very few treatment options. In this phase III study, patients are randomized to either cemiplimab or second-line chemotherapy.
What is the biggest unmet need in cervical cancer?
It is certainly in the second-line setting of treatment, where this study is being conducted. There are no efficient therapies here. This is particularly an issue globally, where this disease is quite common. The opportunity to explore this in an earlier setting of the disease is something that we are interested in.
Rischin D, Gil-Martin M, Gonzalez-Martin A, et al. Cemiplimab, a human PD-1 antibody, in patients with recurrent or metastatic cervix cancer: interim data from phase I cohorts. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract 958P.