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A novel chemo-immunotherapy approach has shown promising results in treating advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), according to researchers at the University of Chicago Medicine Comprehensive Cancer Center. The Phase 2, non-randomized clinical trial found that more than half of participants experienced significant tumor shrinkage following treatment with the immunotherapy drug nivolumab combined with chemotherapy, followed by response-adaptive chemo-radiation therapy. The findings were recently published in JAMA Oncology.
Challenges in Treating Advanced HPV-Negative HNSCC
HPV-negative HNSCC primarily affects older patients with a history of heavy smoking and alcohol use. These patients often experience poor treatment outcomes and diminished quality of life. While early-stage (Stage 1 or 2) cases can be treated effectively with surgery or radiation, many patients are diagnosed at later stages (Stage 3 or 4), making treatment more challenging and leading to high mortality rates.
Current treatment strategies, including chemo-radiation therapy or surgery, have limited success in improving survival for advanced, non-metastatic HPV-negative HNSCC. Furthermore, these treatments can significantly impact speech, swallowing, and overall well-being. The study aimed to address two key challenges: enhancing survival rates and optimizing treatment to minimize long-term side effects.
Neoadjuvant Immunotherapy: A Promising Strategy
“Immunotherapy, particularly immune checkpoint inhibitors, has transformed treatment for recurrent or metastatic head and neck cancers, but its role in curative settings has been limited until now,” said Dr. Ari Rosenberg, Assistant Professor of Medicine at UChicago Medicine and the study’s corresponding author.
Neoadjuvant therapy, which involves administering treatment before surgery or radiation, was the focus of this study. Researchers evaluated the effects of three cycles of neoadjuvant chemotherapy combined with nivolumab, followed by chemo-radiation therapy. Patients who exhibited more than 50% tumor shrinkage were assigned to a de-escalation treatment arm, while the remaining patients received standard chemo-radiation therapy.
Survival Benefits and Tumor Response
The primary objective of the trial was to determine the deep response rate—defined as the proportion of patients achieving at least 50% tumor shrinkage with neoadjuvant chemo-immunotherapy. Results indicated that 53% of participants reached this milestone, surpassing expectations based on historical chemotherapy data.
Higher programmed death-ligand 1 (PD-L1) expression was associated with more pronounced tumor shrinkage, suggesting that PD-L1 could serve as a biomarker for predicting treatment response and potential survival benefits.
In addition to tumor response rates, the study examined overall survival, treatment-related toxicity, and patient quality of life. The findings revealed that the chemo-immunotherapy approach not only improved survival rates but also led to reduced treatment toxicity and enhanced patient well-being, particularly among those in the de-escalation treatment group.
Future Implications
“To our knowledge, this is the first study evaluating neoadjuvant chemo-immunotherapy followed by response-adaptive de-escalation treatment in non-surgical HPV-negative HNSCC patients,” said Dr. Rosenberg. “These encouraging results could shape new treatment strategies that improve both survival outcomes and quality of life.”
Other contributors to the study include researchers from the University of Chicago and Rush University Chicago.
For further details, the full study is available in JAMA Oncology under the title Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Patients should consult their healthcare providers for personalized treatment options.
