Neil D. Gross, MD, FACS, discusses key safety data from a phase 2 study of neoadjuvant cemiplimab in cutaneous squamous cell carcinoma.

Dr Gross on the Safety of Neoadjuvant Cemiplimab in Stage II/IV CSCC

Neil D. Gross, MD, FACS, surgeon-scientist, director, Clinical Research, the Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, discusses key safety data derived from additional follow-up of a phase 2 study (NCT04154943) evaluating neoadjuvant cemiplimab (Libtayo) in cutaneous squamous cell carcinoma (CSCC), as well as highlights the implications of these data for continued research.

The non-randomized, multicenter study, evaluated neoadjuvant cemiplimab followed by surgery with curative intent in patients with stage II-IV cutaneous CSCC. Subsequent treatment in part 2 of the study, which included up to 48 weeks of adjuvant cemiplimab, radiotherapy, or observation only, was determined by investigator discretion.

At a median follow-up of 18.7 months, the study revealed a 1-year event-free survival (EFS) rate with the cemiplimab regimen of 89.0% (95% CI, 79.1%-94.3%) in the overall population. Patients who achieved a pathologic complete response (pCR) following surgery had even more favorable outcomes, with a 12-month EFS of 94.9% (95% CI, 81.0%-98.7%) and no disease recurrence. Conversely, patients who did not undergo surgery or were non-responders demonstrated a lower estimated 12-month EFS of 72.0% (95% CI, 43.8%-87.7%).

Regarding safety, neoadjuvant cemiplimab was generally well tolerated, with 89% of patients experiencing a treatment-emergent adverse effect (TEAE) of any grade and 19% experiencing a TEAE of grade 3 or higher, Gross details. Among the 16 patients who received adjuvant cemiplimab per investigator discretion, there were 4 grade 3 TEAEs, including 2 grade 3 serious AEs of worsening cardiomyopathy and hypophysitis, he adds. Notably, no deaths related to the study drug occurred in this subgroup.

These findings, which were presented at the 

, suggest that the neoadjuvant approach with cemiplimab may be beneficial for patients with resectable CSCC, Gross states. The encouraging results warrant further investigation in a randomized phase 3 setting to establish its efficacy and safety as a standard treatment approach for this patient population, he concludes.

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Neil D. Gross, MD, FACS, discusses a phase 2 study evaluating neoadjuvant cemiplimab in cutaneous squamous cell carcinoma.

Dr Gross on the Background of Investigating Neoadjuvant Cemiplimab in CSCC

Neil D. Gross, MD, FACS, surgeon-scientist, director, Clinical Research, Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses the rationale for launching a phase 2 study (NCT04154943) evaluating neoadjuvant cemiplimab (Libtayo) in patients with cutaneous squamous cell carcinoma (CSCC), highlighting 1-year follow-up data derived from the study.

, EFS data were presented for the entire patient cohort and stratified by pCR as determined by independent central pathologic review. These findings were simultaneously published in 

As of the December 1, 2022, cutoff date, the median follow-up was 18.7 months, he continues. 

 revealed that the estimated 12-month event-free survival (EFS) rate with cemiplimab was 89.0% (95% CI, 79.1%-94.3%) in the entire population (n = 79). Among patients who achieved a pathologic complete response (pCR; n = 40), the estimated 12-month EFS rate was notably higher at 94.9% (95% CI, 81.0%-98.7%). Notably, patients showing pathologic response exhibited more favorable EFS rates compared with those who underwent no surgery or showed no response, Gross concludes.

The phase 2 trial enrolled patients with resectable CSCC ranging from stages II to IV, Gross begins. Of note, the trial's primary end point was pCR, reflecting the remarkable responses observed with cemiplimab in preliminary data, he adds. During the trial, the decision regarding adjuvant treatment was left to the discretion of the investigators due to the perceived impracticality of specifying it beforehand, Gross says. Consequently, investigators could opt for patients to receive adjuvant cemiplimab for up to 48 weeks, adjuvant radiation, or observation, he emphasizes. The patient population in this trial represented the typical demographic profile of patients with advanced CSCC, which predominantly affects White males and older individuals, Gross expands, noting that the trial included a patient as old as 93 years, which is not an unusual age for patients with this disease.


Neil D. Gross, MD, FACS, surgeon-scientist, director, Clinical Research, the Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, discusses 1-year follow-up data from a phase 2 study (NCT04154943) of neoadjuvant cemiplimab (Libtayo) in cutaneous squamous cell carcinoma (CSCC).

In part 1 of this non-randomized, multicenter study, patients with stage II-IV CSCC received neoadjuvant cemiplimab followed by surgery with curative intent. Subsequent treatment in part 2 was determined by investigator discretion, and included up to 48 weeks of adjuvant cemiplimab, radiotherapy, or observation only.

Results demonstrated a robust 1-year event-free survival (EFS) rate with the cemiplimab regimen, Gross says. After a median follow-up of 18.7 months, the estimated 12-month EFS was 89.0% (95% CI, 79.1%-94.3%) for patients in the overall population (n = 79), he reports. This included a major pathologic response rate of 88.9% (95% CI, 43.3%-98.4%) and a pathologic partial response rate of 100.0% (95% CI, not evaluable [NE]- NE). Notably, the 40 patients who achieved a pathologic complete response (pCR) had more favorable outcomes, achieving a 12-month EFS of 94.9% (95% CI, 81.0%-98.7%) and experiencing no disease recurrence, Gross adds. Conversely, those who did not undergo surgery or were non-responders demonstrated an estimated 12-month EFS of 72.0% (95% CI, 43.8%-87.7%).

Lastly, the estimated 12-month overall survival (OS) rate for the overall patient cohort was 92%, further emphasizing the clinical benefit of this treatment approach. There were no new safety concerns associated with neoadjuvant cemiplimab, indicating that its use in this setting is well-tolerated.

The absence of disease recurrence among patients who achieved a pCR underscores the potential for cemiplimab to enhance long-term disease control and highlights its role in improving patient outcomes. Overall, these findings support the continued investigation of neoadjuvant cemiplimab in a planned phase 3 trial, Gross concludes.

Neil D. Gross, MD, FACS, discusses 1-year follow-up data from a phase 2 study of neoadjuvant cemiplimab in cutaneous squamous cell carcinoma.

Dr Gross on Updated Survival Outcomes With Neoadjuvant Cemiplimab in CSCC

Neil D. Gross, MD, FACS, surgeon-scientist, director, Clinical Research, the Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, discusses the investigation of cemiplimab (Libtayo) in cutaneous squamous cell carcinoma. 

A phase 2 trial (NCT04154943) evaluated the efficacy of neoadjuvant cemiplimab, as measured by pathologic complete response rate per independent central pathology review, in patients with stage II to IV cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma is a common cancer type, and although the majority of patients are successfully treated with surgery alone, others require more extensive surgery and adjuvant radiation, Gross explains. The cumulative effects of additional therapies can pose a problem to a patient’s quality of life when the disease presents in the head and neck area in proximity to structures critical to speech, vision, and hearing, Gross continues.

The goal of investigating cemiplimab in patients with cutaneous squamous cell carcinoma was to improve oncologic outcomes and functional outcomes for patients who have the disease presents in a high-risk area, Gross concludes.

Neil D. Gross, MD, FACS, discusses the investigation of cemiplimab in cutaneous squamous cell carcinoma. 


Dr. Gross on the Investigation of Cemiplimab in Cutaneous Squamous Cell Carcinoma

Neil D. Gross, MD, FACS, professor and director of Clinical Research, Department of Head and Neck Surgery, Division of Surgery, at The University of Texas MD Anderson Cancer Center, discusses the prognosis of patients who are diagnosed with cutaneous squamous cell carcinoma of the head and neck.

Head and neck cancer encompasses a broad range of cancers that can develop in the mouth, thyroid, skin, salivary glands, and sinuses, says Gross. Each subtype has a different prognosis, he adds. Cutaneous squamous cell carcinoma is one such subset that has been understudied. The primary reason for this is that skin cancers aside from melanoma are too common to account for in national registries.

Early-stage cutaneous squamous cell carcinoma is typically treated in the community setting. Once the disease progresses to an advanced stage, patients are referred to centers of excellence due to the aggressive nature of the disease, concludes Gross.

Neil D. Gross, MD, FACS, discusses the prognosis of patients who are diagnosed with cutaneous squamous cell carcinoma of the head and neck.

Dr. Gross on the Prognosis of Cutaneous Squamous Cell Carcinoma of the Head and Neck

Neil D. Gross, MD, FACS, professor of head and neck surgery, The University of Texas MD Anderson Cancer Center, discusses a phase II study of neoadjuvant cemiplimab (Libtayo) prior to surgery in patients with stage III/IV cutaneous squamous cell carcinoma (cSCC) of the head and neck.

To be included in the trial, patients needed to have advanced cutaneous squamous cell carcinoma with a plan for surgery and radiation, explains Gross. The 20 patients included in the trial received a baseline biopsy and then received 2 doses of therapy before receiving standard-of-care treatment with surgery and planned postoperative radiation.

Results of the trial showed a discrepancy between imaging and pathology results. About one-third of patients showed an imaging response to treatment, according to Gross. With pathologic response, however, more than 11 of the patients had a pathologic complete response and had no cancer at the time of surgery, says Gross. An additional 3 patients showed a major pathologic response, suggesting they could have achieved a complete response with further treatment, Gross concludes.

Neil D. Gross, MD, FACS, discusses a phase II study of neoadjuvant cemiplimab in patients with stage III/IV cutaneous squamous cell carcinoma of the head and neck.

Neil D. Gross, MD, FACS

Articles

Dr Gross on the Safety of Neoadjuvant Cemiplimab in Stage II/IV CSCC

Dr Gross on the Background of Investigating Neoadjuvant Cemiplimab in CSCC

Dr Gross on Updated Survival Outcomes With Neoadjuvant Cemiplimab in CSCC

Dr. Gross on the Investigation of Cemiplimab in Cutaneous Squamous Cell Carcinoma

Dr. Gross on the Prognosis of Cutaneous Squamous Cell Carcinoma of the Head and Neck

Dr. Gross on Neoadjuvant Cemiplimab in Head and Neck CSCC