Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial

Zhanjie Zhang, Bian Wu, Gang Peng, Guixiang Xiao, Jing Huang, Qian Ding, Chengzhang Yang, Xingao Xiong, Hui Ma, Liangliang Shi, Jinsong Yang, Xiaohua Hong, Jielin Wei, You Qin, Chao Wan, Yi Zhong, Yan Zhou, Xueyan Zhao, Yangming Leng, Tao Zhang, Gang Wu, Min Yao, Xiaomeng Zhang, Kunyu Yang, Zhanjie Zhang, Bian Wu, Gang Peng, Guixiang Xiao, Jing Huang, Qian Ding, Chengzhang Yang, Xingao Xiong, Hui Ma, Liangliang Shi, Jinsong Yang, Xiaohua Hong, Jielin Wei, You Qin, Chao Wan, Yi Zhong, Yan Zhou, Xueyan Zhao, Yangming Leng, Tao Zhang, Gang Wu, Min Yao, Xiaomeng Zhang, Kunyu Yang

Abstract

Purpose: This study aimed to assess the antitumor activity and safety of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Patients and methods: In this single-center, single-arm, phase 2 trial, patients with resectable stage III-IVB HNSCC received chemotherapy [albumin-bound paclitaxel 260 mg/m2 (or docetaxel 75 mg/m2) plus cisplatin 75 mg/m2] and camrelizumab 200 mg on day 1 of each 21-day cycle for three cycles, followed by surgery, and adjuvant radiotherapy. Co-primary end points were pathological complete response (pCR) rate and safety.

Results: Thirty patients were enrolled and completed the neoadjuvant therapy, with an objective response rate (ORR) of 96.7% (29/30). Twenty-seven patients underwent surgery without delay, with an R0 resection rate of 92.6% (25/27). The clinical to pathological downstaging rate was 100% (27/27). The pCR rate was 37.0% [95% confidence interval (CI), 19.4%-57.6%], and the major pathological response (MPR) rate was 74.1% (95% CI, 53.7%-88.9%). The median follow-up duration was 16.1 months (range, 8.3-28.5), and the disease-free survival rate at 12 months was 95.8% (95% CI, 73.9%-99.4%). Grade 3 neoadjuvant therapy-related adverse events included rash (1; 3.3%), pruritis (1; 3.3%), and thrombocytopenia (1; 3.3%), and no grade 4 or 5 treatment-related events occurred. The most common surgical complication was delayed wound healing (5; 18.5%).

Conclusions: Neoadjuvant chemotherapy plus camrelizumab for locally advanced HNSCC showed high ORR, pCR, and MPR rates, with an acceptable safety profile. These data support further evaluation of neoadjuvant chemoimmunotherapy for the treatment of locally advanced HNSCC.

©2022 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Trial flow diagram.
Figure 2.
Figure 2.
Tumor response. A, Treatment response of individual patients who underwent surgery (n = 27). The red horizontal line represents 30% target lesion reduction. B, Swimming plot of disease-free survival for individual patients (n = 30). CPS, combined positive score; HPV, human papilloma virus; NA, not available.
Figure 3.
Figure 3.
Significant tumor response was observed in the radical specimens. A and B, Fibrosis, lymphocyte infiltration, necrosis, cholesterol clefts (arrow), giant cell reaction, and calcification in primary tumor with pathological complete response (pCR). Hematoxylin–eosin, magnifications, ×100 (A) and ×200 (B). C, An aggregation of macrophages into the regression bed of HPV+ subject with pCR. Hematoxylin–eosin, magnifications, ×200. D, Acellular keratin and residual viable tumor (arrow) in the primary tumor with major pathological response (MPR). Hematoxylin–eosin, magnifications, ×200. E and F, Necrosis, histiocytes, cholesterol clefts, and giant cell reaction in metastatic lymph node with pCR. Hematoxylin–eosin, magnifications, ×40 (E) and ×100 (F). F is an enlargement within the square of E.
Figure 4.
Figure 4.
Tumor regression in a 61-year-old man with stage IVA hypopharyngeal cancer (T2N2cM0, P21). The tumor was PD-L1 positive (combined positive score = 10) and originated in the left pyriform sinus. A, Pretreatment image showed a cT2 squamous cell carcinoma of the left pyriform sinus. B, Pretreatment MR imaging showed bilateral cervical lymph nodes. C and D, After three cycles of neoadjuvant chemoimmunotherapy, image at the time before surgery demonstrates near-complete clinical regression of primary lesion as well as cervical lymph nodes. E and F, Pathological findings of biopsy specimens of hypopharyngeal masses before treatment. The tumor is non-keratinizing squamous cell carcinoma with papillary features. Hematoxylin–eosin, magnifications, ×30 (E) and ×200 (F). G and H, Histopathologic images of the resection specimen after treatment. Fibrosis, lymphocyte infiltration, and histiocytes aggregation (arrow) were found in the regression bed, and no cancer residue was found (pathological complete response).Hematoxylin–eosin, magnifications, ×30 (G) and ×200 (H).

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