In an interview with Targeted Oncology, Danny Rischin, MD, director, discussed the findings from the EMPOWER-CSCC-1 study of cemiplimab in advanced cutaneous squamous cell carcinoma that led to the drug’s FDA approval.
Cemiplimab (Libtayo) received its approval from the FDA in September 2018 for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation, and this therapy has now become the standard of care for this patient population.
The approval of this PD-1 inhibitor for cutaneous squamous cell carcinoma was based on findings from the phase 2 EMPOWER-CSCC-1 study and 2 expansion cohorts from the phase 1 Study 1432 trial, but longer-term findings from the EMPOWER-CSCC-1 trial have showed continued responses in this patient population. Longer-term follow-up from this study was recently presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting.
According to the 3-year follow-up, the trial demonstrated a clinically meaningful improvement with cemiplimab in patients with advanced cutaneous squamous cell carcinoma. The overall response rate (ORR) was 46.1%, which included a complete response (CR) rate of 16.1%. The median time to CR was 11.2 months, and the duration of response had not yet been reached, nor the overall survival (OS).
The Kaplan-Meier estimated probability of OS was 73.3% (95% CI, 66.1%-79.2%). The estimated median progression-free survival for all patients was 18.4 months (95% CI, 10.3-24.3), and the Kaplan-Meier estimated progression-free survival rate was 44.2% at 24 months (95% CI, 36.1%-52.1%).
In an interview with Targeted Oncology, Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, discussed the findings from the EMPOWER-CSCC-1 study of cemiplimab in advanced cutaneous squamous cell carcinoma that led to the drug’s FDA approval.
TARGETED ONCOLOGY: What are what were the initial data seen with this agent that led to its approval?
Rischin: Cemiplimab is a monoclonal antibody directed against the PD-1 receptor, and it's been tested in this phase 2 trial in patients with advanced cutaneous squamous cell carcinoma. These are patients who no longer have metastatic disease and [are not eligible for] curative surgery or radiotherapy. In the data, the initial analyses from this study led to its registration approval in many jurisdictions around the world that have established this as the standard of care for patients advanced cutaneous squamous cell carcinoma. The report presented at ASCO this year represent longer follow up and updated data.
TARGETED ONCOLOGY: Could you elaborate on the phase 2 trial, what it examined, who it is examining, and the methods of design?
Rischin: The phase 2 trial enrolled patients with advanced cutaneous squamous cell carcinoma, and there were 2 groups, including patients that had metastatic, including nodal, disease and patients who had advanced disease, so they were no longer suitable for surgical treatment or for radiotherapy. Among the eligibility criteria, it's important to emphasize these were immunocompetent patients, so patients who were immunosuppressed were not eligible for this study. There's been a number of groups enrolled, and the initial registration was based on the early groups. We presented the pooled analysis of groups 1-3; groups 1 and 3 enrolled patients with metastatic disease, and group 2 was advanced disease. Groups 1 and 2 received weight-based dosing of the cemiplimab, given every 2 weeks, and group 3 received a flat-dose of 350 mg every 3 weeks.
TARGETED ONCOLOGY: What does the longer term follow up data look like?
Rischin: The key findings are this demonstrates the durability of responses. One of the impressive things over time with successive analysis is the increasing CR rate. If we look at what the ORR is, if you pull 193 patients, the ORR is 46%. If you look at group 1, where in the first analysis, the CR rate was 77%, and second analysis was 17%. It's now up to 20%, so patients were treated for a maximum 2 years, but we're seeing increasing durability of responses and even responses improving over time.
Now in terms of the duration of response, 88% of responses are ongoing in 12 months and 70% at 24 months, so most patients who responded with a CR or partial response have an ongoing response. If you look at the OS, 75% of patients alive at 2 years. Previously with available treatments, the average survival was no more than 15 months, so it's a marked improvement in outcomes for these patients who previously had incurable disease.
TARGETED ONCOLOGY: How do you think this agent compares with others in this space?
Rischin: I think it's important to remember that this is an elderly population. The median age was 72 years, and the oldest patient on study was 96, so it's a bit different than your average oncology study. For previous agents, we had chemotherapy and perhaps EGFR inhibitors. They weren't well tolerated by this population. The responses were generally a short duration, and many patients weren't treated because it wasn't thought to be in their interest to treat them. On the other hand with cemiplimab, the great majority of patients, despite age, can be treated. There's no suggestion that people who are elderly, respond any differently or have any experience different. This is a drug you can give this population, irrespective of age, expecting a high probability of response and benefit.
TARGETED ONCOLOGY: Are there any other efforts being made evaluating the use of this agent further that you wanted to highlight?
Rischin: With the exciting results in the advanced setting, there's now intense interest about whether you could move this drug up into earliest stages of disease and improve outcomes. Particularly in the advanced setting where surgery and post-operative radiotherapy are the standard, we've identified from previous work that there are high-risk groups that still don't do that well with the standard treatment, and we are running an adjuvant study now which is looking at these high-risk patients after they've had surgery and radiotherapy, randomizing them between cemiplimab and placebo. This will be an important trial to establish whether giving it earlier in the disease can improve survival.
Along similar lines, there's been some preliminary data using adjuvant cemiplimab in the same group of patients showing a very high response rate in a preliminary study. Based on that, there are further studies being done exploring that approach as well.
TARGETED ONCOLOGY: Were there any other data presented this year at ASCO in cutaneous squamous cell carcinoma that you want to highlight?
Rischin: There’s another abstract looking at the impact of cemiplimab in these patients on quality of life, showing improvement in quality of life and improvements in pain control. This suggests not just durable responses but ongoing tangible symptomatic benefit to patients.
TARGETED ONCOLOGY: What would you say is your take home message to your colleagues regarding this work?
Rischin: Cemiplimab is a very effective treatment for advanced cutaneous squamous cell carcinoma; it’s the standard of care, and you can actually treat the great majority of patients. There are a few contraindications, but age is not a contraindication. You can treat expecting high probability of response, and the majority of the responses will be durable.