Abstract
ObjectiveSeveral anti-programmed cell death 1 (anti-PD-1) antibodies have demonstrated potential efficacy in the treatment of advanced esophageal squamous cell cancer (ESCC). However, the response to subsequent chemotherapy after the failure of PD-1 blockade in ESCC patients has not been reported, and the optimal sequencing of immunotherapy and chemotherapy remains controversial. The aim of the present study was to evaluate responses to irinotecan-based subsequent chemotherapy in advanced ESCC patients who had progressed after treatment with camrelizumab (SHR-1210), a novel anti-PD-1 antibody.MethodsWe retrospectively reviewed the medical records of patients with advanced ESCC treated with camrelizumab at a single institution. Consecutive patients who received subsequent irinotecan-based chemotherapy were selected for data collection and analysis.ResultsOverall, a total of 28 patients were included. All patients had received at least two lines of systemic treatment prior to irinotecan salvage. The most common regimen that was administered after PD-1 blockade was irinotecan in combination with 5-fluorouracil (5-Fu) (or its derivatives), which was given to 19 patients. The objective response rate (ORR) and disease control rate (DCR) were 17.9% (5/28) and 64.3% (18/28), respectively, with 5 (17.9%) patients achieving a partial response and 13 (46.4%) having stable disease. The median progression-free survival (PFS) was 3.18 [95% confidence interval (95% CI), 2.48−3.88] months and the median overall survival (OS) was 6.23 (95% CI, 4.71−7.75) months. No new safety issues, either immune-related or otherwise, were observed.ConclusionsOur results suggested that the response to irinotecan-based chemotherapy after PD-1 blockade in advanced ESCC patients appeared similar to that previously observed in patients who had not received PD-1 antibodies, and further study in larger cohorts or randomized trials is warranted to verify our observation.
Highlights
Esophageal cancer ranks the seventh in terms of incidence and the sixth in terms of mortality worldwide, and EasternAsia is among the regions with the highest prevalence [1]
The regimens, dosages and schedules used for irinotecan-based chemotherapy in all patients were determined at the discretion of the treating physician
The investigator-assessed best response to the last chemotherapy regimen received before anti-PD1 antibody was available in 23 of the patients; the objective response rate (ORR) was 14.3% (4/28), and 3 patients achieved partial response (PR) and 1 patient achieved complete response (CR)
Summary
Esophageal cancer ranks the seventh in terms of incidence and the sixth in terms of mortality worldwide, and EasternAsia is among the regions with the highest prevalence [1]. Active anti-tumor agents for the treatment of advanced ESCC are extremely limited, especially in patients whose disease progresses after first-line chemotherapy. Gefitinib, an EGFR-tyrosine kinase inhibitor (TKI), did not prolong overall survival (OS) in a randomized phase 3 trial in which both esophageal adenocarcinoma and ESCC patients were enrolled, and the benefit in terms of PFS was only marginal [5]. Likewise, icotinib, another EGFR-TKI, showed limited efficacy in a selected population of pretreated ESCC patients with EGFR overexpression or amplification [6]. Given the lack of effective targeted agents, rechallenge chemotherapy, preferably with regimens not received in previous lines of therapy, is a reasonable choice in the post PD-1 blockade setting
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