A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma

Shetal A Patel; Michael K Gibson; Allison Deal; Siddharth Sheth; Hillary Heiling; Steven M Johnson; Kathe Douglas; Melissa Flores; Jeffrey Blumberg; Catherine Lumley; Wendell G Yarbrough; Colette Shen; Bhishamjit S Chera; Jessica R Bauman; Trevor Hackman; Jared Weiss

doi:10.1002/cncr.34930

A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma

Cancer. 2023 Nov 1;129(21):3381-3389. doi: 10.1002/cncr.34930. Epub 2023 Jul 3.

Authors

Shetal A Patel^{1

2}, Michael K Gibson³, Allison Deal², Siddharth Sheth^{1

2}, Hillary Heiling², Steven M Johnson⁴, Kathe Douglas², Melissa Flores², Jeffrey Blumberg⁵, Catherine Lumley⁵, Wendell G Yarbrough⁵, Colette Shen⁶, Bhishamjit S Chera⁷, Jessica R Bauman⁸, Trevor Hackman⁵, Jared Weiss¹

Affiliations

¹ Division of Medical Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
² Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center and the Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
⁴ Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁵ Department Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶ Department of Radiation Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁷ Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina, USA.
⁸ Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

PMID: 37395170
DOI: 10.1002/cncr.34930

Abstract

Background: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established.

Methods: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC. The primary end point was a hypothesized pathologic complete response rate of 50%. After chemo-immunotherapy and surgical resection, patients received study-defined, pathologic risk adapted adjuvant therapy consisting of either durvalumab alone (low risk), involved field radiation plus weekly cisplatin and durvalumab (intermediate risk), or standard chemoradiation plus durvalumab (high risk).

Results: Between December 2017 and November 2021, 39 subjects were enrolled at three centers. Oral cavity was the most common primary site (69%). A total of 35 of 39 subjects underwent planned surgical resection; one subject had a delay in surgery due to treatment-related toxicity. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. Post treatment imaging demonstrated an objective response rate of 57%. Pathologic complete response and major pathologic response were achieved in 29% and 49% of subjects who underwent planned surgery, respectively. The 1-year progression-free survival was 83.8% (95% confidence interval, 67.4%-92.4%).

Conclusions: Neoadjuvant carboplatin, nab-paclitaxel, and durvalumab before surgical resection of HNSCC were safe and feasible. Although the primary end point was not met, encouraging rates of pathologic complete response and clinical to pathologic downstaging were observed.

Keywords: durvalumab; head and neck cancer; neoadjuvant chemo-immunotherapy; oral cavity; oropharynx.

Grants and funding

AstraZeneca