Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: A retrospective, single-center, three-arm study

Abstract

Background Pembrolizumab has been approved by the Food and Drug Administration (FDA) for the first-line treatment of locally advanced or metastatic esophageal cancer. This study investigated the efficacy and safety of pembrolizumab combined with paclitaxel and platinum for the treatment of locally advanced and potentially resectable esophageal squamous cell carcinoma (ESCC). Methods In this retrospective, single-center, three-arm study, patients with locally advanced and potentially resectable ESCC received pembrolizumab (200 mg on day 1) in combination with paclitaxel (135 mg/m2 on day 1) and nedaplatin (100 mg/m2 on day 1) as induction therapy once every 3 weeks. After 4 cycles of systemic therapy in the first stage, patients who chose to undergo radical surgery were divided into group A, patients who underwent radical radiotherapy were divided into group B, and patients who did not undergo any radical therapy were divided into group C. Maintenance treatment with pembrolizumab was performed in all 3 groups. The efficacy and safety of pembrolizumab were evaluated through clinical data, such as the objective response rate (ORR), progression-free survival (PFS), and safety assessment. Results From August 2019 to June 2022, a total of 39 patients were included in this study. After immune response evaluation in the first stage, 34 (87.2%) patients achieved immune partial response (iPR), and 5 (12.8%) patients achieved immune stable disease (iSD). The ORR was 87.1% (27/31), and the disease control rate (DCR) was 100%. Twenty-two patients in group A underwent surgery, and all patients underwent R0 resection. The major pathological response (MPR) rate was 68.2% (15/22), and the pathological complete response (pCR) rate was 45.5% (10/22). Nine patients in group B chose radiotherapy as the radical therapeutic method after the tumors had shrunk significantly. Eight patients in group C did not undergo any radical therapy. All patients received maintenance treatment with pembrolizumab, and the median period of pembrolizumab therapy was 8 cycles (4–22 cycles). The median follow-up time was 16.6 months (6–34 months), and the median overall survival (OS) and PFS times were not reached in either groups A or B. The incidence of severe adverse events (AEs) (grade ≥ 3) was 15.4% (6/39), and the main treatment-related AEs were rash and hypothyroidism. One patient stopped treatment after 4 cycles of induction therapy due to a severe rash. There was no significant difference in the incidence of AEs between groups A and B. Conclusions Pembrolizumab in combination with paclitaxel and platinum as induction therapy for locally advanced and potentially resectable ESCC has a high ORR, high surgical conversion, MPR, pCR, and R0 resection rates, and tolerable AEs in the operation group. For patients unwilling to undergo surgical treatment, pembrolizumab could provide good benefits in sequential treatment with radical radiotherapy or maintenance therapy. This treatment model in different clinical scenarios is worth further exploration in the field of immunotherapy for locally advanced and potentially resectable ESCC.