抗 PD-1 治疗转移性黑色素瘤的 FDG-PET 反应和结果。

FDG-PET response and outcome from anti-PD-1 therapy in metastatic melanoma.

机构信息

Melanoma Institute Australia and The University of Sydney, Sydney, Australia; Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia.

Melanoma Institute Australia and The University of Sydney, Sydney, Australia; Department of Nuclear Medicine, St Vincent's Hospital, Sydney, Australia; The University of New South Wales, Sydney, Australia.

出版信息

Ann Oncol. 2018 Oct 1;29(10):2115-2120. doi: 10.1093/annonc/mdy330.

DOI:10.1093/annonc/mdy330

PMID:30137228

Abstract

BACKGROUND

Immune checkpoint inhibitor therapy has resulted in impressive and durable clinical activity for many cancers including melanoma; however, there remain few reliable predictors for long-term response. This study investigated whether [18F]2-fluoro-2-deoxy-D-glucose (FDG-PET) imaging may better predict long-term outcomes compared with standard computed tomography (CT) response criteria.

PATIENTS AND METHODS

Retrospective analysis of metastatic melanoma patients treated with anti-PD-1-based immunotherapy with baseline and 1-year FDG-PET and CT imaging at Melanoma Institute Australia. One-year response was determined using RECIST for CT and EORTC criteria for PET, coded as complete response (CR or CMR), partial response (PR or PMR), stable disease (SD or SMD) or progressive disease (PD or PMD). Progression-free survival (PFS) was determined from the 1-year landmark.

RESULTS

Patients (n = 104) were evaluated with median follow-up 30.1 months and 98% remain alive. Most received anti-PD-1 as monotherapy (67%) or combined with ipilimumab (31%). At 1 year, 28% had CR, 66% had PR and 6% had SD on CT, while 75% had CMR, 16% PMR and 9% SMD/PMD on PET. CMR was observed in 68% of patients with PR on CT. RECIST PFS post 1-year landmark was similar in patients with CR versus PR/SD, but improved in patients with CMR versus non-CMR {median not reached [NR] versus 12.8 month; hazard ratio [HR] 0.06 [95% confidence interval (CI) 0.02-0.23]; P < 0.01}. In patients with PR on CT, PFS was improved in patients with PR + CMR versus PR + non-CMR (median NR versus 12.8 months; HR 0.07 [95% CI 0.02-0.27]; P < 0.01). In the 78 CMR patients, 78% had discontinued treatment and 96% had ongoing response.

CONCLUSIONS

Whilst only a small proportion of patients have a CR at 1 year, most patients with a PR have CMR on PET. Almost all patients with CMR at 1 year have ongoing response to therapy thereafter. PET may have utility in predicting long-term benefit and help guide discontinuation of therapy.

摘要

背景

免疫检查点抑制剂治疗在包括黑色素瘤在内的许多癌症中取得了令人印象深刻且持久的临床疗效；然而，目前仍然缺乏可靠的长期反应预测指标。本研究旨在探讨与标准 CT 反应标准相比，[18F]2-氟-2-脱氧-D-葡萄糖（FDG-PET）成像是否可以更好地预测长期结局。

患者和方法

对在澳大利亚黑色素瘤研究所接受抗 PD-1 为基础的免疫治疗的转移性黑色素瘤患者进行回顾性分析，这些患者在基线和 1 年时进行了 FDG-PET 和 CT 成像。使用 CT 的 RECIST 和 PET 的 EORTC 标准，将 1 年时的反应编码为完全缓解（CR 或 CMR）、部分缓解（PR 或 PMR）、疾病稳定（SD 或 SMD）或疾病进展（PD 或 PMD）。从 1 年的时间点开始确定无进展生存期（PFS）。

结果

患者（n=104）中位随访时间为 30.1 个月，98%的患者仍存活。大多数患者接受了抗 PD-1 单药治疗（67%）或联合 ipilimumab 治疗（31%）。在 1 年时，CT 上有 28%的患者有 CR，66%的患者有 PR，6%的患者有 SD，而 PET 上有 75%的患者有 CMR，16%的患者有 PMR，9%的患者有 SMD/PMD。在 CT 上有 PR 的患者中，有 68%的患者有 CMR。在 1 年的时间点之后，CR 患者的 RECIST PFS 与 PR/SD 患者相似，但 CMR 患者的 PFS优于非 CMR 患者{中位无进展生存期未达到[NR]与 12.8 个月；风险比[HR]0.06[95%置信区间（CI）0.02-0.23]；P<0.01}。在 CT 上有 PR 的患者中，PR+CMR 患者的 PFS优于 PR+非 CMR 患者（中位无进展生存期 NR 与 12.8 个月；HR 0.07[95%CI 0.02-0.27]；P<0.01）。在 78 名 CMR 患者中，78%的患者停止了治疗，96%的患者仍有反应。