Service de Gastroentérologie et d'Oncologie Digestive, Hôpital Européen George Pompidou, Université de Paris, AP-HP, Paris, France.
Service d'Anatomie et Cytologie Pathologique, Hôpital Ambroise Paré, AP-HP, Paris, France.
Dig Liver Dis. 2021 Oct;53(10):1254-1259. doi: 10.1016/j.dld.2021.06.009. Epub 2021 Jun 30.
Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high". The first patient was included on April 20, 2021.
派姆单抗是一种 PD1 免疫检查点抑制剂（ICI），最近有报道称，在微卫星不稳定/缺陷错配修复转移性结直肠癌（MSI/dMMR mCRC）患者中，它的疗效非常显著，与微卫星稳定/熟练错配修复（MSS/pMMR）mCRC 患者不同，后者的 ICI 通常无效。然而，大约 15%的 MSS/pMMR CRC 被肿瘤浸润淋巴细胞高度浸润。此外，奥沙利铂和贝伐珠单抗都被证明具有免疫调节特性，可能会提高 ICI 的疗效。我们提出了这样的假设，即具有高免疫浸润的 MSS/pMMR mCRC 患者可能对 ICI 联合奥沙利铂和贝伐珠单抗为基础的化疗敏感。POCHI 是一项多中心、开放标签、单臂 II 期试验，旨在评估 Pembrolizumab 联合 Capox Bevacizumab 作为高免疫浸润 MSS/pMMR mCRC 的一线治疗的疗效，我们计划招募 55 名患者。主要终点是 10 个月时的无进展生存期（PFS），预计大于 50%，但希望达到 70%。主要次要目标是总生存期、二次切除率和反应深度。患者必须已经切除了原发肿瘤，以便评估两种不同的免疫评分（Immunoscore®和 TuLIS），如果一种评分“高”，则符合条件。第一个患者于 2021 年 4 月 20 日入组。
