Less invasive treatment identified for HPV-unrelated head and neck cancer
Key findings:
- Three-fourths of patients achieved an overall major pathologic or complete response after receiving a combination of radiation and immunotherapy.
- Patients who achieved treatment response experienced an increase in effector T cells, a decrease in immunosuppressive cells and an increase in antigen presentation after treatment.
Stereotactic body radiation therapy combined with single-dose durvalumab before surgery appeared safe and induced durable responses among patients with HPV-unrelated locally advanced head and neck cancer, according to study results.
The findings of the phase 1/1b study, published in Nature Cancer, laid the groundwork for a larger, ongoing phase 2 trial.
Background and methods
The 5-year survival rate for HPV-unrelated head and neck squamous cell carcinomas is below 50%, according to study background.
Laurel B. Darragh, MD/PhD student in the department of immunology at University of Colorado Denver-Anschutz Medical Campus, and colleagues sought to assess the safety of hypofractionated SBRT with neoadjuvant single-dose durvalumab among 21 patients (median age, 61 years; 67% men; 66.7% heavy smokers) with HPV-unrelated head and neck squamous cell carcinoma.
Most patients (85.7%) had subsite oral cavity cancer, 90.5% had T3 disease or higher and 67% had node-positive disease. Approximately one-fourth (24%) received prior irradiation.
Safety served as the primary endpoint. Radiographic, pathologic and objective response rates, locoregional control, PFS and OS served as secondary endpoints.
Median follow-up was 16 months.
Results
Results showed an overall major pathologic or complete response rate of 75% (95% CI, 51.6-100).
Researchers observed an OS rate of 80.1% (95% CI, 62-100) and locoregional control and PFS rate of 75.8% (95% CI, 57.5-99.8).
Of note, none of those in the expansion cohort with major pathologic or complete response received adjuvant radiotherapy or chemotherapy despite large tumors at presentation, and no recurrences occurred.
Researchers used high-dimensional multi-omics and spatial data, as well as biological correlatives, to show that patients who achieved treatment response experienced an increase in effector T cells, a decrease in immunosuppressive cells and an increase in antigen presentation after treatment.
Implications
“The response in our patients to this dual-treatment protocol surpassed our expectations,” Sana Karam, MD, PhD, associate professor of radiation oncology at University of Colorado Cancer Center, said in a press release. “By combining treatment modalities, we were able to spare our patients’ lymph nodes and prime their immune systems, ultimately resulting in a less morbid treatment regimen.
“Our biggest takeaway from these results is hope for our patients,” Karam continued. “The response rates here are truly unparalleled, so we are hopeful that this work will lead to a significantly improved standard of care in how we treat these types of cancers.”
References:
- CU Anschutz researchers find less invasive treatment for certain head and neck cancers (press release). Available at: news.cuanschutz.edu/cancer-center/cu-anschutz-researchers-find-less-invasive-treatment-for-certain-head-and-neck-cancers#. Published Nov. 28, 2022. Accessed Jan. 5, 2023.
- Darragh LB, et al. Nat Cancer. 2022;doi:10.1038/s43018-022-00450-6.
Perspective
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The use of immunotherapy with radiation in the nonsurgical management of head and neck cancer has been explored in randomized controlled trials and, thus far, results have been disappointing. However, this study adds to promising early-phase data indicating a possible benefit of neoadjuvant immunotherapy with surgical resection. The hypothesized limitation of immunotherapy with radiation in head and neck cancer is that standard fractionated radiotherapy — approximately 30 treatments — and the associated treatment area results in immunosuppression, dampening the effect of immunotherapy. In contrast, SBRT — administered in a high dose over only one to five treatments to a limited region — can possibly potentiate immunotherapy secondary to different biological effects.
The response of head and neck SCC to immunotherapy traditionally has been less than 40%. This study demonstrates a robust response with 75% of patients — treated with a minimum of 18 Gy in three treatments — developing a major or complete pathological response, indicating a probable positive interaction between immunotherapy and SBRT. Additionally, the pathologic response rate increased as the dose of radiation was escalated. Later in the study, patients who experienced a complete response or major pathology response with no pathologically positive nodes went on to receive adjuvant immunotherapy alone.
This study presents promising early evidence that preoperative immunotherapy and SBRT appears safe, does not delay definitive surgical resection, and results in promising pathologic response rates. This study also presents a host of translational information to aid understanding of the immune response. It is important to release these informative early results; however, additional follow-up will be important for definite clinical outcomes. Patterns of failure will be key in determining if the combination of SBRT and immunotherapy results in not only local effect but sterilization of micrometastatic disease not apparent at diagnosis. The impact of SBRT on additional factors such as postoperative complications and long-term toxicity of tissues remaining in situ will be of interest. Overall, should this innovative paradigm continue to demonstrate positive results, this may represent a means for improving outcome for a cohort of patients plagued by poor outcomes without substantial improvement in decades.
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