SHR‐1316 , an anti‐PD‐L1 antibody, plus chemotherapy as the first‐line treatment for advanced esophageal squamous cell carcinoma: A multicentre, phase 2 study

Abstract Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) have a poor prognosis with few treatment options. Immunotherapy was suggested as a promising treatment for ESCC from some clinical trials. Here we collected clinical results from 23 patients who were received anti-PD1/PDL1 antibodies (mAbs) plus chemotherapy as first line therapy with advanced ESCC, to analyze this combined therapy’s efficacy on advanced ESCC. Methods: Results of 23 Patients started treatment from December 15th, 2017 to September 27th, 2019 (12 patients were enrolled in phase II clinical trials, 11 patients were treated by physician’s choice regiment) of anti-PD1/PDL1 antibodies (mAbs) plus chemotherapy on advanced ESCC as first line treatment were collected. Regiments were either anti-PD1 or anti-PDL1 mAbs plus traditional chemotherapy (cisplatin/5-fluorouracil (5-FU), Paclitaxel/ cisplatin, Paclitaxel/carboplatin or Paclitaxel/ 5-FU) every 3 weeks for six cycles, followed by maintenance therapy with anti-PD1/PDL1 mAbs. Objective response and safety profiles were observed as well as progression-free survival(PFS), overall survival(OS) and duration of response. Results: Of the 23 patients, 18 (78.3%) responded to treatment: 15 partial and 3 complete response. 4 patients had stable disease and 1 patient had progressive disease. The median time to response was 1.4 months (range, 1.4 months – 2.8 months). Treatment-related adverse events occurred in all patients but 3-4 grade immune-mediated adverse events occurred in only one patient. As of April 10th, 2020, the Objective response rate was 78.3%, the median PFS was 15.5 months and the median OS was 21.5 months. No treatment-related deaths were observed. Conclusions: Anti-PD1/PDL1 antibodies plus chemotherapy as the first-line treatment for advanced ESCC showed promising results with manageable adverse events and worthy of further study.

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Phase 2 study of camrelizumab (anti-PD-1 antibody) combined with apatinib and chemotherapy for the first-line treatment of advanced esophageal squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4033 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4033-4033 ◽

Cited By ~ 5

Author(s):

Bo Zhang ◽

Ling Qi ◽

Xi Wang ◽

Jun Jiang ◽

Xin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Locally Advanced ◽

Line Treatment ◽

Phase 2 ◽

First Line ◽

Phase 2 Study ◽

Grade 3 ◽

First Line Treatment ◽

Liposomal Paclitaxel

4033 Background: Both anti-PD-1 antibodies and molecular antiangiogenic agents have shown promising anti-tumor activities in patients with advanced esophageal cancer. We conducted this single-center phase 2 study to evaluate the efficacy and safety of camrelizumab (anti-PD-1 antibody) plus apatinib (VEGFR2-TKI) in combination with liposomal paclitaxel and nedaplatin in the first-line treatment of patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with unresectable locally advanced or metastatic ESCC received camrelizumab 200mg d1, liposomal paclitaxel 150mg/m2 d1, nedaplatin 50mg/m2 d1 and apatinib 250mg d1-14. Treatments were repeated every 14 days for up to 6-9 cycles, followed by maintenance therapy with camrelizumab, apatinib, or both. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated by immunohistochemistry (IHC). Results: Between Aug 6th 2018 and Feb 6th 2019, a total of 29 patients were enrolled. The median age was 62 years (43-70). Most patients were male (22/29, 75.9%) with metastatic disease (25/29, 86.2%). Response evaluation by independent central review was available in 26 patients, with 19 achieving a best response of PR, 6 with SD, and 1 with PD. The ORR and DCR were 73.1% (19/26) and 96.2% (25/26), respectively. Data for PFS and OS were not matured. The most common grade 3/4 adverse events were leucopenia (21/29, 72.4%) and neutropenia (15/29, 51.7%). Two cases of treatment-related SAEs occurred, both led to hospitalization: one patient developed grade 3 febrile neutropenia, grade 4 leucopenia and grade 3 anorexia; another patient developed grade 4 toxic epidermal necrolysis. Conclusions: Camrelizumab plus apatinib in combination with liposomal paclitaxel and nedaplatin could be a new treatment option for patients with unresectable locally advanced or metastatic ESCC. Clinical trial information: NCT03603756.

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