Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma

Abstract

BackgroundProgrammed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC.MethodsPatients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6–9 weeks after the first cycle.ResultsBetween January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3–4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1+ CD163+ cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017).ConclusionsNeoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC.Trial registration numberChiCTR2000028900.

Efficacy and safety of camrelizumab in combination with neoadjuvant chemotherapy for ESCC and its impact on esophagectomy

“…Yang W et al. ( 29 ) used a neoadjuvant regimen consisting of camrelizumab, nab-paclitaxel, and carboplatin for esophageal cancer, and the final pCR rate was 25% (5/23). Yang P et al.…”

Case Report: First-Line Immunotherapy for Esophageal Squamous Carcinoma Combined With Hypopharyngeal Squamous Carcinoma Yields Sustained Survival Benefit

“…All of the above aspects may be closely related to the sustained survival benefit of this patient after receiving treatment. It has been reported that priming of CD4+ and CD8+ T cells contributes to signaling to cytotoxic T lymphocytes and further establishes effective and durable antitumor immunity ( 31 ), unfortunately, in this patient, changes of tumor-infiltrating CD4+ and CD8+ lymphocytes were not monitored during treatment, and it is not clear whether the patient’s durable immune response is related to the increase in CD4+ and CD8+ after treatment.…”

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis

“…Of the 21 studies included, there were 20 single-arm open-label cohort studies ( 15 , 19 – 37 ) and there was one two-arm open-label randomized controlled trial (RCT) ( 38 ). Of the 21 studies included, three are still ongoing ( 26 , 29 , 30 ) and 18 ( 15 , 19 – 25 , 27 , 28 , 31 – 38 ) have been completed. The main neoadjuvant immunotherapy drugs include pembrolizumab, sintilimab, and camrelizumab, amongst others.…”