Abstract

Background

Immune checkpoint inhibitors anti-PD-1 (Nivolumab and Pembrolizumab) represent a remarkable advance in non-small-cell lung cancer (NSCLC) treatment with impressive clinical activity and durable responses in some patients. However, immunotherapies generate new toxicity profiles called immune-related adverse events (irAEs) that require specific management. Gastrointestinal (GI) irAEs (diarrhea and colitis) are among the most common and if they are left unrecognised or untreated, they can become life threatening. Therefore, the identification of the risk factors for the development of diarrhea could be helpful for the prevention and management of GI irAEs. Among these, the presence of diverticulosis could affect the onset of diarrhea.

Methods

This retrospective analysis was conducted in 94 patients with metastatic NSCLC who received Nivolumab at the Papa Giovanni XXIII Hospital in Bergamo between 2015 and 2017. We evaluated the presence of diverticulosis before the start of immunotherapy, the degree and management of diarrhea during therapy and the correlation between the presence of diverticulosis and GI irAEs.

Results

All patients had previously been treated with chemotherapy. 90 patients received Nivolumab at a dose of 3mg/kg while 4 patients received Nivolumab flat dose of 240mg. The RR was 14% and the DCR was 45%. The median PFS has not yet been reached. 19 of 94 patients had a radiological diagnosis of diverticulosis before the start of treatment and 11 of 94 patients developed diarrhea during the therapy. While of the 75 patients without diverticulosis only 7% developed diarrhea, 32% of patients with diverticulosis developed diarrhea. The chi-square test was used for statistical analysis. GI irAEs were in most cases of grade 2 and were treated with steroid therapy without having to resort to other types of immunosuppressive therapy. No patient discontinued treatment due to adverse event.

Conclusion

In our population, the presence of diverticulosis increases the risk of gastrointestinal irAEs. However, these patients can be treated with immunotherapy but they represent a risk class for the onset of diarrhea. Further studies are needed to confirm our findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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72P免疫检查点抑制剂治疗肺癌患者憩室病与腹泻发作之间的相关性评估

抽象的

背景

免疫检查点抑制剂抗PD-1（Nivolumab和Pembrolizumab）代表了非小细胞肺癌（NSCLC）治疗中的显着进步，在某些患者中具有令人印象深刻的临床活性和持久响应。但是，免疫疗法会产生新的毒性反应，称为免疫相关不良事件（irAEs），需要进行特殊处理。胃肠道（GI）irAE（腹泻和结肠炎）是最常见的疾病，如果不加识别或不加以治疗，可能会危及生命。因此，确定腹泻发展的危险因素可能有助于预防和管理胃肠道irAEs。其中，憩室病的存在会影响腹泻的发作。

方法

这项回顾性分析是对2015年至2017年在贝加莫的Papa Giovanni XXIII医院接受Nivolumab的94例转移性NSCLC患者进行的。我们评估了免疫治疗开始前憩室病的存在，治疗期间腹泻的程度和管理及其相关性在憩室病和胃肠道irAEs之间。

结果

所有患者以前都接受过化学疗法治疗。90例患者接受3mg / kg的Nivolumab剂量，而4例患者接受240mg的Nivolumab固定剂量。RR为14％，DCR为45％。尚未达到中位PFS。94例患者中有19例在开始治疗之前接受了放射诊断，诊断为憩室病； 94例患者中有11例在治疗期间出现腹泻。在75名无憩室病的患者中，只有7％出现腹泻，而32％的憩室病患者发生了腹泻。卡方检验用于统计分析。胃肠道irAEs在大多数情况下为2级，并接受类固醇疗法治疗，而不必诉诸其他类型的免疫抑制疗法。没有患者因不良事件而中断治疗。

结论

在我们的人群中，憩室病的存在增加了胃肠道irAE的风险。但是，这些患者可以接受免疫治疗，但代表腹泻的危险类别。需要进一步研究以确认我们的发现。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

所有作者均声明没有利益冲突。