Neoadjuvant-Intent Immunotherapy in Advanced, Resectable Cutaneous Squamous Cell Carcinoma.

in JAMA otolaryngology-- head & neck surgery by Emily Y Kim, Emily S Ruiz, Mia S DeSimone, Sophia Z Shalhout, Glenn J Hanna, David M Miller, Chrysalyne Schmults, Eleni M Rettig, Ruth K Foreman, Rosh Sethi, Manisha Thakuria, Ann W Silk

TLDR

  • This study looked at how well patients with advanced skin cancer responded to a type of treatment called immunotherapy. The study included 27 patients who were treated with neoadjuvant-intent programmed cell death protein 1 (PD-1) ICIs. Most of the patients were male and had a history of lymphoma. The study found that the treatment was effective in reducing the size of the tumors in most patients. However, some patients did not want to have surgery to remove the tumors because they were responding well to the treatment. The study also found that the treatment was effective in reducing the size of the tumors in patients with a history of lymphoma. The study supports the idea that this type of treatment can be effective in treating skin cancer in the clinical setting. However, the study also suggests that the treatment might not be as effective in patients with certain risk factors or who prefer nonsurgical treatment. Future research should focus on finding ways to improve the effectiveness of this treatment and to identify which patients are most likely to benefit from it.

Abstract

In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Median follow-up was 9.5 months (range, 1.2-40.5). Cemiplimab or pembrolizumab. Primary outcomes were radiologic and pathologic response rates. Secondary outcomes were 1-year recurrence-free survival, progression-free survival, disease-specific survival, and overall survival. This cohort study included 27 patients (including 9 patients [33.3%] with a history of lymphoma). Most patients were male (18 of 27 [66.7%]), with a median age of 72 years (range, 53-87 years). Most primary tumors were located on the head/neck (21 of 27 [77.8%]). There were no unexpected delays in surgery. The median number of doses before surgery was 3.5 (range, 1.0-10.0). Five patients (18.5%) ultimately declined to undergo planned surgery due to clinical responses or stability, and 1 (3.7%) did not undergo surgery due to progressive disease. The overall pathologic response rate (pathological complete response [pCR] or major pathological response) was 47.4% (9 of 19), and the overall radiologic response rate (radiologic complete response or partial response) was 50.0% (8 of 16). The pCR rate (7 of 19 [36.8%]) was higher than the radiologic complete response rate (2 of 16 [12.5%]). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%. The 1-year recurrence-free survival rate was 90.9% (95% CI, 50.8%-98.7%), progression-free survival was 83.3% (95% CI, 27.3%-97.5%), disease-specific survival was 91.7% (95% CI, 53.9%-98.8%), and overall survival was 84.6% (95% CI, 51.2%-95.9%). The results of this cohort study support the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.

Overview

  • The study evaluated radiologic and pathologic response rates to neoadjuvant-intent programmed cell death protein 1 (PD-1) ICIs in a clinical population of patients with advanced cutaneous squamous cell carcinoma (cSCC).
  • The study included 27 patients, including 9 with a history of lymphoma, and most were male with a median age of 72 years. Most primary tumors were located on the head/neck. There were no unexpected delays in surgery, and the median number of doses before surgery was 3.5. Five patients declined to undergo planned surgery due to clinical responses or stability, and 1 did not undergo surgery due to progressive disease. The overall pathologic response rate was 47.4%, and the overall radiologic response rate was 50.0%.

Comparative Analysis & Findings

  • The study found that the pCR rate (7 of 19) was higher than the radiologic complete response rate (2 of 16). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%.

Implications and Future Directions

  • The study supports the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. The inclusion of higher-risk patients and preference for nonsurgical treatment might explain the numerically lower pathologic response rate in this institutional experience. Future research should focus on identifying predictors of response to neoadjuvant-intent immunotherapy and improving patient selection for these treatments.
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