Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: a US Food and Drug Administration pooled analysis.
Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: a US Food and Drug Administration pooled analysis.
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DOI：
10.1016/s1470-2045(17)30846-x
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发表时间：
2018-03
期刊：
影响因子：
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通讯作者：
Theoret MR
中科院分区：
文献类型：
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作者：
Beaver JA;Hazarika M;Mulkey F;Mushti S;Chen H;He K;Sridhara R;Goldberg KB;Chuk MK;Chi DC;Chang J;Barone A;Balasubramaniam S;Blumenthal GM;Keegan P;Pazdur R;Theoret MR
接受免疫治疗的患者可能会出现非典型应答模式，这需要进一步研究在RECIST定义的疾病进展后继续免疫治疗的患者的潜在获益和风险。进行了一项汇总分析，包括向美国食品药品监督管理局（FDA）提交的所有支持抗PD-1抗体上市申请并经FDA批准用于治疗不可切除或转移性黑色素瘤（MM）患者的资料，以评价进展后治疗（TBP）的潜在获益和安全性。试验必须允许在抗PD-1组中持续使用超过RECIST定义的进展（RECISTPD）的抗体。任何在RECISTPD日期后接受抗PD-1抗体的患者均被纳入TBP队列，并在基线和进展时与未接受进展后治疗（noTBP）的队列进行连续分析。TBP队列中的患者在相对于PD和基线TL负荷分析的进展后具有靶病变（TL）缓解。在接受免疫治疗的2624例合并患者中，52%（1361/2624）发生疾病进展（PD）;其中，51%（692/1361）在RECIST定义的进展之外继续接受抗PD-1抗体治疗。TBP队列中有19%（95/500）具有可评价评估的患者的肿瘤负荷降低≥ 30%，当考虑RECISTPD时的负荷作为参考时，占这些TBP的14%（95/692）和所有免疫治疗患者的3.6%（95/2624）。TBP组的总生存率（OS）高于非TBP组。其中一项汇总试验是一项双盲、随机化、活性对照试验，评价抗PD-1抗体与化疗，其中两组中接受治疗超过进展且时间长于noTBP队列的患者的OS相似。TBP队列和非TBP队列之间从停药起90天内的免疫相关不良事件（irAE）相似。不建议在这些免疫疗法的产品标签中继续使用TBP，因为其临床获益仍有待证实。TBP联合抗PD-1抗体治疗可能适用于在进展时根据特定标准确定的特定MM患者，这是基于在已知毒性特征背景下的迟发缓解潜力。没有一
Patients who receive immunotherapeutics may develop an atypical response pattern, which warrants further investigation into the potential benefits and risks for patients who continue immunotherapy beyond RECIST-defined disease progression. A pooled analysis including all submissions to U.S. Food and Drug Administration (FDA) in support of marketing applications for anti-PD-1 antibodies and approved by FDA for treatment of patients with unresectable or metastatic melanoma (MM) was conducted to evaluate the potential benefits and safety of treatment beyond progression (TBP). Trials had to allow for continuation of the antibody beyond RECIST-defined progression (RECISTPD) in the anti-PD-1 arm. Any patient receiving the anti-PD-1 antibody after their RECISTPD date were included in the TBP cohort and analyzed descriptively at baseline and at time of progression with the cohort not receiving treatment beyond progression (noTBP). Patients in the TBP cohort had target lesion (TL) response after progression analyzed relative to PD and baseline TL burden. Of 2624 pooled patients receiving immunotherapy, 52% (1361/2624) had progressive disease (PD); of these, 51% (692/1361) received continued anti-PD-1 antibody beyond RECIST-defined progression. Nineteen percent (95/500) of patients in TBP cohort with evaluable assessments experienced a ≥ 30% decrease in tumor burden, when considering burden at RECISTPD as the reference, representing 14% (95/692) of those TBP and 3·6% (95/2624) of all immunotherapy treated patients. Overall survival (OS) was greater in the TBP cohort compared with the noTBP cohort. One of the pooled trials was a double-blind, randomized, active-controlled trial evaluating an anti-PD-1 antibody vs. chemotherapy in which OS appeared similar in both arms for patients treated beyond progression and longer than the noTBP cohorts. Immune-related adverse events (irAE) up to 90-days from discontinuation were similar between the TBP cohort and the noTBP cohort. Continuation of TBP in the product labeling of these immunotherapies has not been recommended as the clinical benefit remains to be proven. TBP with anti-PD-1 antibody therapy may be appropriate for select patients with MM, identified by specific criteria at the time of progression, based on the potential for late responses in the setting of the known toxicity profile. none