Neoadjuvant Cemiplimab Prolongs Survival in Stage II to IV CSCC


Treatment with neoadjuvant cemiplimab (Libtayo) followed by surgery with curative intent prolonged event-free survival (EFS) in patients with stage II to IV cutaneous squamous cell carcinoma (CSCC), according to Neil D. Gross, MD, FACS, who added that these outcomes warrant further investigation in a randomized setting.

One-year follow-up data from a non-randomized, multicenter, phase 2 study (NCT04154943) were presented at the 2023 ESMO Congress, and showed that the estimated 12-month EFS rate was 89.0% (95% CI, 79.1%-94.3%) in the overall population (n = 79). Patients who experienced a pathologic complete response (pCR; n = 40) experienced an estimated 12-month EFS rate of 94.9% (95% CI, 81.0%-98.7%). The estimated 12-month EFS rates in those who achieved a major pathologic response (n = 10) or a pathologic partial response (n = 7) were 88.9% (95% CI, 43.3%-98.4%) and 100.0% (95% CI, not evaluable [NE]- NE), respectively. In those who did not undergo surgery or who were nonresponders (n = 22), the estimated 12-month EFS rate was 72.0% (95% CI, 43.8%-87.7%). The 12-month overall survival (OS) rate in all patients was 92% (95% CI, 83%-96%).

“We’re seeing that the neoadjuvant approach is broadly encouraging across the oncology community, and in particular, among patients with skin malignancies,” said Gross, who is a surgeon-scientist, as well as the director of clinical research in the Department of Head and Neck Surgery at the University of Texas MD Anderson Cancer Center, in Houston. “Patients with resectable CSCC are likely to benefit from the neoadjuvant approach, and it warrants being tested in a randomized phase 3 setting.”

In an interview with OncLive®, Gross further discussed the phase 2 study investigating neoadjuvant cemiplimab in patients with CSCC and highlighted key efficacy and safety findings with the approach in this population.

OncLive: What was the rationale for launching this trial? Were there any previously reported data that led to its inception?

The impetus for this trial was a pilot study that was performed at the University of Texas MD Anderson Cancer Center and started in 2017. That was a single-institution study that included 20 patients, and the pathologic responses observed in that study led to the phase 2 trial.

Please describe the study design.

The phase 2 trial included 79 patients with stage II to IV resectable CSCC. Importantly, the primary end point of the trial was pCR, based on the pilot data that we saw, which showed exceptional responses.

In the trial, the adjuvant portion was left to the investigator’s discretion. The reason for this was that at the time of the trial, it was felt to be unfeasible to dictate the adjuvant portion of the trial. Therefore, the investigators were allowed to choose between adjuvant cemiplimab for up to 48 weeks vs adjuvant radiation vs observation.

What did the patient population look like?

The patient population included in this trial is typical for patients with advanced CSCC. [The disease is] most prominent in White male patients and in an elderly population. In fact, the oldest patient on the trial was 93 years old, which is not uncommon for this disease.

What updated results were presented at the 2023 ESMO Congress?

We [were] excited to share the survival outcomes from the phase 2 trial. We presented the EFS, disease-free survival, and OS, according to pathologic response by independent central pathologic review. These data [were also] concurrently published in Lancet Oncology.

We presented EFS [data] for the entire cohort of patients, as well as according to pCR by independent central pathologic review. With a data cutoff date of December 1, 2022, we reported a median follow-up of 18.7 months, and observed a 12-month estimated EFS rate of 89% for the overall cohort, and 95% for the patients who had a pCR by independent central pathologic review. In fact, the EFS for patients with any pathologic response was favorable compared to those who had either no surgery or who were nonresponders.

What was learned with regard to the safety of adjuvant cemiplimab?

In the trial, 16 patients received adjuvant cemiplimab per investigator discretion. In these [patients,] there were 4 [grade 3] treatment-emergent adverse effects [AEs], including 2 serious AEs of worsening cardiomyopathy and hypophysitis. Overall, adjuvant cemiplimab was well tolerated.

What should be taken away from these results?

Our study demonstrates favorable oncologic results [in terms of] survival for patients with resectable stage II to IV CSCC treated with neoadjuvant cemiplimab. The EFS rate of 89% for the entire cohort stacks very favorably against the current standard of care. These data support a phase 3 trial, which is currently in development.


Gross ND, Miller DM, Khushalani NI, et al. Neoadjuvant cemiplimab and surgery for stage II–IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study. Lancet Oncl. 2023;24(11):1196-1295. doi:10.1016/S1470-2045(23)00459-X

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