The findings, published Sept. 2 in JAMA Otolaryngology Head & Neck Surgery, are noteworthy because the need for effective treatments in head and neck cancers is critical. It is the sixth most common malignancy in the world largely because of tobacco use and alcohol consumption and long-term outcomes are generally poor.
Currently, the standard care for patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) includes the surgical removal of the tumor followed by chemotherapy and radiotherapy. Despite new treatments, including pembrolizumab and nivolumab for platinum-refractory advanced head and neck squamous cell carcinoma (HNSCC), there are high rates of recurrence.
“The emerging approach of neoadjuvant immunotherapy for solid cancers has set the ground for the integration of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors into the neoadjuvant setting of head and neck squamous cell carcinoma treatment,” wrote the authors of the review which was led by Nidal Muhanna, MD, PhD, Tel Aviv Sourasky Medical Center, Tel Aviv University. “The results [of this analysis] demonstrated favorable outcomes and acceptable tolerance of the administration of neoadjuvant PD-1\PD-L1 inhibitors.”
The analysis included 10 studies
The review included 10 cohort studies and randomized clinical trials of 344 patients who were undergoing treatment for HNSCC between 2015 and 2021. In eight studies, patients received neoadjuvant immunotherapy, and in two studies, patients received combined immunotherapy with neoadjuvant chemotherapy and/or radiotherapy.
The overall pathological response rate was 9.7% (95% confidence interval, 3.1%-18.9%) for primary tumors treated with neoadjuvant immunotherapy or, 2.9% (95% CI, 0%-9.5%) for the pathological complete response rate (with a range of 0%-16.7%).
Treatment with neoadjuvant immunotherapy was ultimately found to be statistically significant (odds ratio, 0.07; 95% CI, 0.03-0.18). Plus, favorable associations for treatment with neoadjuvant immunotherapy were found with nodal pathological complete response. In two studies cited in the analysis, combination treatment with neoadjuvant immunotherapy and chemotherapy and/or radiation before surgery had an overall pathological complete response rate of 53%.
The major pathologic response in which less than 10% of the tumor remained after treatment varied greatly between 2.9% and 31.0% in five studies. The mean major pathologic response in these cases was 9.7%, which suggested a statistically significant association. A major pathologic response for lymph nodes was described in three studies as statistically significant for neoadjuvant immunotherapy.
In terms of adverse events, 8.4% (95% CI, 0.2%-23.2%) of patients were treated for autoimmune colitis, duodenal hemorrhage, mucositis, nausea, vomiting, and syncope.
Combination treatment with neoadjuvant immunotherapy with chemotherapy or radiotherapy continues to be evaluated in clinical trials (NCT03721757, NCT03635164, and NCT03618134). “Whether these combinations have synergistic effects or provide any therapeutic benefit, compared with single-agent therapy is still under investigation. It has been hypothesized that chemotherapy preceding the administration of neoadjuvant immunotherapy may increase antigen presentation by dendritic cells and enhance immune activation against the tumor, which can potentially increase therapeutic efficacy,” the authors wrote.
Other ongoing clinical trials will report survival data in the upcoming years. One of these trials is the IMSTAR-HN, a phase 3 clinical trial assessing neoadjuvant nivolumab with and without ipilimumab as first-line treatment with curative intent for HNSCC. It will report disease-free survival, overall survival, and progression-free survival outcomes.
The authors reported no disclosures.