Danny Rischin, MD, is a professor and director of Medical Oncology at the Peter MacCallum Cancer Centre

Dr Rischin on the Safety of Adjuvant Cemiplimab in High-Risk CSCC

“This is the first trial to show in a clinically meaningful and statistically significant way that an adjuvant therapy, in this case, adjuvant cemiplimab, can improve the outcome for these patients with advanced disease, and this represents a new potential standard-of-care option for both patients and their oncologists to consider.”

Danny Rischin, MD, professor and director of Medical Oncology at the Peter MacCallum Cancer Centre, discussed the safety profile of adjuvant cemiplimab-rwlc (Libtayo) in patients with high-risk cutaneous squamous cell carcinoma (CSCC). During the randomized phase 3 C-POST trial (NCT03969004), investigators evaluated the tolerability of cemiplimab compared with placebo following surgery in this patient population. The duration of exposure was similar between the 2 arms, with a median of approximately 48 weeks.

Findings showed that treatment-emergent adverse effects (TEAEs) of any grade occurred in 91% of patients who received cemiplimab (n = 205) and in 89% of those who received placebo (n = 204). Grade 3 or higher TEAEs were observed more frequently with cemiplimab (24%) compared with placebo (14%). Any-grade serious TEAEs were reported in 18% of patients in the cemiplimab arm vs 9% of those in the placebo arm. Treatment discontinuations due to any-grade TEAEs occurred in 10% of patients receiving cemiplimab and 1% of those receiving placebo. Fatal TEAEs of any grade occurred in 1% of patients in each arm.

Treatment-related TEAEs were observed in 62% of cemiplimab-treated patients, including 10% of patients with grade 3 or higher effects, compared with 46% and less than 1% of patients, respectively, in the placebo group. Immune-mediated AEs were more common in the cemiplimab arm (23% any grade; 7% grade ≥ 3) than in the placebo arm (6% any grade; 0% grade ≥ 3). The most frequent any-grade TEAEs occurring in at least 10% of patients included fatigue (22% in both arms), pruritus (cemiplimab arm, 16%; placebo arm, 12%), rash (16%; 9%), diarrhea (16%; 19%), arthralgia (13%; 12%), hypothyroidism (12%; 3%), and maculopapular rash (11%; 6%). Most effects were low grade.

Rischin emphasized that the safety profile of adjuvant cemiplimab was consistent with what has been observed with other anti–PD-1 monotherapies and with cemiplimab in the advanced setting. No unexpected toxicities were reported, and treatment was generally well tolerated. Importantly, he noted that this trial represents the first to demonstrate in a statistically significant and clinically meaningful manner that adjuvant cemiplimab can improve outcomes in patients with high-risk CSCC following surgery.

Rischin concluded that these findings support adjuvant cemiplimab as a potential new standard-of-care option for this population, offering patients and oncologists an evidence-based approach to reducing recurrence risk without introducing new safety concerns.

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Danny Rischin, MD, discusses safety findings from the phase 3 C-POST trial of adjuvant cemiplimab vs placebo in patients with high-risk CSCC.

Dr Rischin on the Efficacy of Adjuvant Cemiplimab in High-Risk CSCC

"We showed a marked [DFS] improvement with cemiplimab compared with placebo."

Danny Rischin, MD, a professor and director of Medical Oncology at the Peter MacCallum Cancer Centre, discussed key efficacy findings from the phase 3 C-POST trial (NCT03969004) investigating adjuvant cemiplimab-rwlc (Libtayo) vs placebo in patients with high-risk cutaneous squamous cell carcinoma (CSCC).

C-POST is a double-blind trial evaluating the efficacy and safety of the PD-1–targeting antibody cemiplimab vs placebo in high-risk patients with CSCC who have received surgery and postoperative radiotherapy. Patients defined as high-risk met criteria such as nodal disease, T4 lesions, or perineural invasion. The primary end point was disease-free survival (DFS).

Rischin reported that cemiplimab is the only systemic therapy to demonstrate a statistically significant and clinically meaningful reduction in disease recurrence in the adjuvant setting. The study demonstrated a marked improvement in DFS with cemiplimab (n = 205) compared with placebo (n = 204), including a 68% reduction in the risk of recurrence or death (HR, 0.32; 95% CI, 0.20-0.51; 

< 0001). The median DFS was not reached in the cemiplimab arm, and was 49.4 months (range 48.5-not evaluable) in the placebo arm. The 2-year DFS rate was 87.1% in the cemiplimab arm vs 64.1% in the placebo arm. 

The benefit of adjuvant cemiplimab was observed across all prespecified subgroups examined. This included patients regardless of age (younger than 65 years of age, HR, 0.40, 95% CI, 0.17-0.92; at least 65 years of age, HR, 0.30, 95% CI, 0.17-0.53) and high-risk category (nodal disease, HR, 0.36, 95% CI, 0.19-0.67; non-nodal disease, HR, 0.27, 95% CI, 0.13-0.56). The improvement in DFS was attributed to reductions in both locoregional and distant recurrence. Freedom from locoregional recurrence showed an 80% reduction (HR, 0.20; 95% CI, 0.09-0.40), whereas freedom from distant recurrence showed a 65% reduction (HR, 0.35; 95% CI, 0.17-0.72). Similar efficacy was observed across cemiplimab dosing schedules.

Safety data showed that the profile of cemiplimab in the adjuvant setting was consistent with its known profile. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 91% of patients in the cemiplimab group vs 89% of those in the placebo group. Grade 3 or higher TEAEs occurred in 24% of patients in the cemiplimab group vs 14% of those in the placebo group. Immune-mediated AEs were reported in 23% of patients who received cemiplimab vs 6% of those who received placebo. Rischin concluded that adjuvant cemiplimab represents a potential new standard of care for patients at high risk of CSCC recurrence.

Danny Rischin, MD, discusses key DFS data from the phase 3 C-POST trial of adjuvant cemiplimab vs placebo in patients with high-risk CSCC.

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.

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

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