Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the phase III KEYNOTE-048 trial, which examines pembrolizumab (Keytruda) or pembrolizumab plus chemotherapy versus EXTREME as first-line therapy for patients with recurrent/metastatic head and neck squamous cell carcinoma.

The regimens were investigated in 3 populations: patients who had a PD-L1 combined positive score (CPS) of ≥20 and ≥1, and in the overall population. Pembrolizumab monotherapy versus EXTREME showed significantly improved OS in patients with PD-L1 CPS ≥20 and CPS ≥1. In the total population, pembrolizumab monotherapy showed no PFS improvements and was noninferior, but it did not meet the superiority threshold. Response rates were lower with pembrolizumab monotherapy versus EXTREME in the overall population, but the duration of response was longer. The adverse event (AE) profile showed that there were less serious AEs in patients who received pembrolizumab monotherapy.

The pembrolizumab plus chemotherapy combination versus EXTREME also improved overall survival in all 3 populations. The pembrolizumab monotherapy and combination arms had similar response rates, PFS, and AE profiles.

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Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, discusses the phase III KEYNOTE-048 trial, which examines pembrolizumab or pembrolizumab plus chemotherapy versus EXTREME as first-line therapy for patients with recurrent/metastatic head and neck squamous cell carcinoma.

Dr. Rischin on KEYNOTE-048 Results in Head and Neck Squamous Cell Carcinoma

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the role of cemiplimab (Libtayo) in the treatment of patients with cervical cancer.

A study presented at the 2018 ESMO Congress evaluated the use of cemiplimab, an anti—PD-1 monoclonal antibody, in multiple expansion cohorts. Two of the cohorts included patients with advanced or recurrent cervical cancer. One of these cohorts assessed the use of cemiplimab monotherapy in this population, while the other looked at cemiplimab with hypofractionated radiotherapy.

Patients with recurrent or metastatic cervical cancer resistant to platinum and taxane doublet chemotherapy were given cemiplimab at 3 mg/kg every 2 weeks for up to 48 weeks. Patients who were randomized to the combination also received radiotherapy at 3 times per week, starting 1 week after the first dose of cemiplimab.

Results from the open-label, international, phase I GOG 3016/ENGOT-cx 9 study (NCT03257267), showed an investigator-assessed overall response rate (ORR) of 10% in the 2 10-patient cohorts treated with the immunotherapy agent; the disease control rate in both cohorts were 20%. The median time to response for those who received cemiplimab monotherapy was 1.84 months versus 1.77 months in those who were given the combination.

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the role of cemiplimab in the treatment of patients with cervical cancer.

Dr. Rischin Discusses Role of Cemiplimab in Cervical Cancer

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the next steps with cemiplimab (Libtayo) in the treatment landscape of cervical cancer.

Cemiplimab is currently being investigated in a phase III study of patients with recurrent or metastatic platinum-refractory cervical cancer (NCT03257267). Phase I results presented at the 2018 ESMO Congress showed that the anti—PD-1 agent had antitumor activity both alone and in combination with hypofractionated radiotherapy in patients with recurrent or metastatic cervical cancer.

There are no effective therapies in the second-line setting for these patients, Rischin says. If cemiplimab is successful in the phase III trial, it could fill that unmet need. Additionally, Rischin suggests that per a positive phase III trial, it would be wise to study this agent in the first-line recurrent metastatic setting, and even earlier as adjuvant treatment for patients in the curative setting. Cemiplimab has the potential to have a global impact, as the rate of cervical cancer continues to climb across the world.  

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the next steps with cemiplimab (Libtayo) in the treatment landscape of cervical cancer.
 

Dr. Rischin Discusses the Future of Cemiplimab in Cervical Cancer

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the use of cemiplimab (Libtayo) in patients with cervical cancer.

In a phase I dose-escalation study, cemiplimab showed promising efficacy in patients with recurrent or metastatic cervical cancer who progressed after frontline platinum-based therapy. These patients, Rischin says, have few options, noting that chemotherapy has not been found to be effective.

Activity was observed in the cervical cancer cohorts. There was 1 partial response in each cohort, and multiple patients had durable control without progression, reports Rischin. Additionally, an acceptable safety profile was observed, and single agent cemiplimab is currently being evaluated in a phase III randomized study versus chemotherapy (NCT03257267).

The PD-1 inhibitor cemiplimab was approved by the FDA in September 2018 for the treatment of patients with metastatic cutaneous squamous cell carcinoma or patients with locally advanced disease who are not candidates for curative surgery or curative radiation.

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses the use of cemiplimab (Libtayo) in patients with cervical cancer.
 

Dr. Rischin Discusses Cemiplimab in Cervical Cancer

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses cemiplimab in cutaneous squamous cell carcinoma (CSCC).

In April 2018, the FDA granted a priority review to a biologics license application for the PD-1 inhibitor cemiplimab for the treatment of patients with metastatic CSCC or those with locally advanced CSCC who are not eligible for surgery. This was based on data from the phase II EMPOWER-CSCC 1 study (NCT02760498).

According to findings presented at the 2018 ASCO Annual Meeting, cemiplimab induced an overall response rate of 47.5% in patients with metastatic CSCC. Additionally, 28 of 59 patients had a response, including 4 (6.8%) partial responses and 24 (40.7%) complete responses at a median follow-up of 7.9 months. The data presented at ASCO were for the cohort of 59 patients with metastatic disease.

The median age of the 59 patients was 71 (range, 38-93), with 43 (73%) patients aged ≥65 years. Most of these patients had been heavily pretreated with radiotherapy or systemic therapy, Rischin noted.

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses cemiplimab in cutaneous squamous cell carcinoma.
 

Danny Rischin, MD

Articles

Dr. Rischin on KEYNOTE-048 Results in Head and Neck Squamous Cell Carcinoma

Dr. Rischin Discusses Role of Cemiplimab in Cervical Cancer

Dr. Rischin Discusses the Future of Cemiplimab in Cervical Cancer

Dr. Rischin Discusses Cemiplimab in Cervical Cancer

Dr. Rischin Discusses Cemiplimab in Cutaneous Squamous Cell Carcinoma