The safety and efficacy of neoadjuvant PD-1 inhibitor with chemotherapy for locally advanced esophageal squamous cell carcinoma

Dijian Shen; Qixun Chen; Jie Wu; Jianqiang Li; Kaiyi Tao; Youhua Jiang

doi:10.21037/jgo-20-599

The safety and efficacy of neoadjuvant PD-1 inhibitor with chemotherapy for locally advanced esophageal squamous cell carcinoma

J Gastrointest Oncol. 2021 Feb;12(1):1-10. doi: 10.21037/jgo-20-599.

Authors

Dijian Shen^{1

2}, Qixun Chen^{1

2}, Jie Wu^{1

2}, Jianqiang Li^{1

2}, Kaiyi Tao^{1

2}, Youhua Jiang^{1

2}

Affiliations

¹ Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
² Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China.

Abstract

Background: Neoadjuvant therapy followed by esophagectomy has been recognized as an effective treatment for locally advanced esophageal cancer, though still has a dismal prognosis. Antibodies against programmed death 1 (PD-1) protein improve survival in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with chemotherapy in second-line therapy. However, neoadjuvant PD-1 inhibitor combined with chemotherapy has not been tested in locally advanced ESCC. We conducted this study to evaluate the efficacy and safety of pd-1 inhibitor in neoadjuvant chemotherapy.

Methods: In this study, we administered 28 adults with untreated, surgically resectable locally advanced ESCC. PD-1 inhibitor with chemotherapy [albumin paclitaxel 100 mg/m² on days 1 and 8 + carboplatin with an area under the curve (AUC) of 5 on day 1] were administered every 3 weeks intravenously, and surgery was performed approximately 3-5 weeks after the second dose. The primary purpose of the study was to evaluate the feasibility and safety of this regimen.

Results: In all, 28 locally advanced ESCC patients were enrolled, 27 patients received surgery, 9 (33.3%) patients' postoperative pathological specimens suggested pCR, and 11 (40.7%) patients' primary tumor suggested complete response. Neoadjuvant PD-1 inhibitor with chemotherapy had an acceptable side-effect profile, 26 patients' tumors were completely resected (96.3% were R0). According to the RESIST v.1.1, the response in all 27 patients was evaluated by a computed tomography (CT) scan before surgery, showing 12 patients with complete response (CR), 12 with partial response (PR), and 3 with stable disease (SD). For surgical procedures, 15 (55.6%) patients underwent minimal invasive surgery, 4 (14.8%) underwent right transthoracic open esophagectomy, and 8 (29.6%) underwent hybrid approaches.

Conclusions: The novel treatment of PD-1 inhibitor with chemotherapy in the neoadjuvant setting for locally advanced ESCC produced satisfactory outcomes: an unprecedentedly high pCR rate for neoadjuvant chemotherapy, a high R0 resection rate, and a low-toxicity profile were achieved. The long-term efficiency of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.

Keywords: Neoadjuvant immunotherapy; esophageal squamous cell carcinoma (ESCC); programmed death 1 (PD-1); thoracic surgery.