Combining the PD-1 inhibitor nivolumab and chemotherapy, and following that regimen with response-adapted chemoradiation, may an effective treatment for advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma, according to a recent study published by Rosenberg et al in JAMA Oncology.
Background
HPV-negative head and neck squamous cell carcinoma is often diagnosed in older patients with a history of heavy smoking and alcohol use. These patients typically experience poor quality of life and treatment outcomes. Although stage I or II HPV-negative head and neck squamous cell carcinoma can be cured with surgery or radiation, many cases are diagnosed at advanced stages as a result of a lack of notable symptoms—thereby making treatment more challenging and mortality rates high.
The current standard treatment for advanced, nonmetastatic HPV-negative head and neck squamous cell carcinoma includes chemoradiation or surgery and offers limited survival benefit. These treatments can also negatively impact speech, swallowing, and overall quality of life. There are, therefore, two major unmet needs in this patient population: higher survival/recurrence rates, and optimized treatments that minimize long-term adverse effects.
“Immunotherapy, specifically immune checkpoint inhibitors, has revolutionized the way we treat recurrent or metastatic head and neck cancers, improving survival outcomes. However, they have not played a significant role in curative intent thus far,” stressed lead study author Ari Rosenberg, MD, Assistant Professor of Medicine at the University of Chicago Medicine.
Study Methods and Results
In the phase II trial, researchers assigned 36 patients with advanced HPV-negative head and neck squamous cell carcinoma to receive a regimen of three cycles of neoadjuvant chemotherapy combined with nivolumab followed by chemoradiation. They sought to evaluate the deep response rate, defined as the proportion of patients who achieved 50% or greater tumor shrinkage with neoadjuvant chemoimmunotherapy.
The researchers found that 53% of the study participants achieved a deep response following receipt of the combination therapy regimen. These patients were assigned to the trial’s de-escalation arm, while the other arm received standard chemoradiation.
“This result exceeded our expectations over our historical data with chemotherapy alone,” Dr. Rosenberg emphasized.
Deeper responses were observed in patients with a higher expression of PD-L1, suggesting that PD-L1 could serve as a potential biomarker to predict treatment response and potential survival benefit.
The researchers also assessed survival outcomes, treatment toxicities, patient function, and quality of life. In high-risk patients with locally advanced stage IV head and neck cancer, the chemoimmunotherapy regimen led to improved survival outcomes and fewer toxic adverse effects—particularly among those who responded favorably to neoadjuvant chemoimmunotherapy and received de-escalated treatment.
Conclusions
“This is [one of] the first studies, to our knowledge, that evaluates neoadjuvant chemoimmunotherapy followed by response-adaptive de-escalation treatment in [patients with] nonsurgical HPV-negative HNSCC,” Dr. Rosenberg underscored. “These promising results pave the way for new treatment paradigms that not only improve survival but also enhance the quality of life for these patients,” he concluded.
Disclosure: The research in this study was supported by a University of Chicago Medicine investigator-initiated clinical trial funded by Bristol Myers Squibb and Celgene, the University of Chicago Medicine Comprehensive Cancer Center Support Grant, and the University of Chicago Medicine Head and Neck Cancer Program. For full disclosures of the study authors, visit jamanetwork.com.
