Nivolumab produces ‘significant clinical activity’ in cutaneous squamous cell carcinoma
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More than half of patients had an objective response to first-line nivolumab for locally advanced or metastatic cutaneous squamous cell carcinoma, phase 2 study results published in Cancer showed.
Investigators reported manageable treatment-related toxicities, with only one patient discontinuing therapy because of effects from the study drug.
The results suggest the anti-PD-1 agent may be another effective immune checkpoint inhibitor for patients with advanced disease who have not received previous systemic therapy.
Background
Few effective options existed for treatment of locally advanced or metastatic cutaneous squamous cell carcinoma before the approval of two anti-PD-1 agents — cemiplimab (Libtayo, Regeneron) and pembrolizumab (Keytruda, Merck) — which have both “emerged as a successful strategy for the management” of advanced disease, Rodrigo R. Munhoz, MD, medical oncologist at Hospital Sírio-Libanês in Brazil, and colleagues wrote.
Munhoz and colleges sought to determine whether nivolumab (Opdivo, Bristol Myers Squibb) would be effective and thereby further establish anti-PD-1 immune checkpoint inhibitors as the standard of care for patients with advanced cutaneous squamous cell carcinoma.
Methodology
The phase 2 CA209-9JC trial evaluated the safety and efficacy of nivolumab among 24 patients (median age, 74 years; range, 48-93) with locally advanced or metastatic cutaneous squamous cell carcinoma who had not received previous systemic treatment.
Participants received nivolumab dosed at 3 mg/kg every 2 weeks until disease progression, unacceptable toxicity or 12 months of treatment.
Best objective response rate (BORR) served as the study’s primary endpoint. Secondary endpoints included PFS, OS and safety.
Median follow-up was 17.6 months.
Key findings
Investigators reported a BORR of 58.3% for the entire study group, with no complete responses to therapy.
Further analysis showed an estimated median PFS of 12.7 months and estimated median OS of 20.7 months. Median duration of response had not yet been reached.
Univariate analysis showed an association between previous radiation therapy and worse outcomes (P = .035).
Twenty-one patients (85.7%) had treatment-related adverse events, with six (25%) experiencing grade 3 or greater events. One patient discontinued nivolumab because of toxicities related to the drug.
Clinical implications
First-line treatment with nivolumab resulted in “significant clinical activity” in patients with advanced cutaneous squamous cell carcinoma who had not previously received systemic treatment, the investigators noted.
“This is the first study to investigate nivolumab in this patient population, and it provides further evidence supporting the use of immune checkpoint blockers as standard therapies in cutaneous squamous cell carcinoma,” Munhoz said in a press release from the American Cancer Society.
Despite being smaller in size than the studies leading to FDA approval of cemiplimab and pembrolizumab for advanced cutaneous squamous cell carcinoma, the study of nivolumab showed “striking similarities” in clinical activity, according to Conor E. Steuer, MD, medical oncologist at Winship Cancer Institute of Emory University, and Nabil F. Saba, MD, FACP, the Lynne and Howard Halpern chair in head and neck cancer research at Winship Cancer Institute.
“In addition to providing more assurance to the clinical activity of different PD-1 inhibitors in this disease, these replicated data may permit a more widespread utilization of these agents in managing a common disease with global implications,” they wrote in an accompanying editorial. “With the prohibitive cost of anticancer agents in different regions of the world, the disparities in access to care, and the emergence of domestic drug development, the incentive of relying on smaller pilot studies similar to the report by Munhoz [and colleagues] to draw evidence for clinical efficacy of various anticancer agents could be strong.”
References :
- American Cancer Society. Phase II clinical trial generates promising results for immunotherapy drug nivolumab in patients with advanced skin cancer [press release]. Oct. 24, 2022.
- Munhoz RR, et al. Cancer. 2022;doi:10.1002/cncr.34463.
- Steuer CE, et al. Cancer. 2022;doi:10.1002/cncr.34465.
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Perspective
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Emrullah Yilmaz, MD, PhD
Immunotherapy with anti-PD-1 inhibitors has changed the treatment paradigm for locally advanced and metastatic cutaneous squamous cell carcinoma. Cemiplimab and pembrolizumab are two FDA-approved immunotherapy agents for advanced cutaneous squamous cell carcinomas.
This study investigated the role of another anti-PD-1 inhibitor, nivolumab, for the treatment of patients with locally advanced or metastatic cutaneous squamous cell carcinomas. The response rates observed appeared comparable to those reported in prior studies of cemiplimab and pembrolizumab.
Responses to anti-PD-1 inhibitors for patients with advanced cutaneous squamous cell carcinoma can be up to 50% or 60%, as reported in this study. One of the study's key findings is that patients had durable responses, although the treatment was limited to 12 months of nivolumab. Disease control can be achieved for a long time for patients who respond to immunotherapy, and this is one of the most significant benefits of immunotherapy in cutaneous squamous cell carcinoma. However, we still do not have a study showing the ideal duration and when to stop immunotherapy for patients who achieve an early response.
Biomarkers could help us better predict which patients would benefit from immunotherapy. We have not had a promising biomarker for cutaneous squamous cell carcinoma. Patients can get a response to immunotherapy regardless of PD-L1 status. Cutaneous squamous cell carcinomas tend to have a high tumor mutational burden (TMB) in general; therefore, TMB has not been proven as an effective predictive biomarker. Future studies are needed on biomarkers for immunotherapy response in cutaneous squamous cell carcinoma, and this may help us select patients for these treatments.
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