Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study
Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study
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DOI：
10.1016/s1470-2045(21)00097-8
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发表时间：
2021-06-01
期刊：
影响因子：
51.1
通讯作者：
Long, Georgina V.
中科院分区：
文献类型：
--
作者：
da Silva, Ines Pires;Ahmed, Tasnia;Long, Georgina V.
背景抗PD-1治疗（以下简称抗PD-1）可在约30%的转移性黑色素瘤患者中诱导长期疾病控制;然而，三分之二的患者具有耐药性，需要进一步治疗。我们的目的是确定ipilimumab加抗PD-1（pembrolizumab或nivolumab）与ipilimuinab单药治疗抗PD-（L）1治疗（以下简称抗PD-[L]1）耐药患者的疗效和安全性。我们纳入了患有转移性黑色素瘤（不可切除的III期和IV期）的成年患者（年龄≥ 18岁），他们对抗PD-（L）1（先天性或获得性耐药）具有耐药性，然后根据治疗的可用性或医生确定的临床因素或两者接受ipilimumab单药治疗或ipilimumab+抗PD-1（pembrolizumab或nivolumab）。根据标准治疗（CT或PET-CT扫描，每3个月一次）评估肿瘤缓解。研究终点为客观缓解率、无进展生存期、总生存期和ipilimumab联合抗PD-1的安全性。结果我们纳入了355例抗PD-（L）1耐药的转移性黑色素瘤患者（纳武单抗、派姆单抗或阿特珠单抗），在2011年2月1日至2020年2月6日期间接受过伊匹单抗单药治疗（n=162 [46%]）或伊匹单抗联合抗PD-1治疗（n=193 [54%]）。中位随访时间为22.1个月（IQR 9.5-30.9），伊匹单抗联合抗PD-1治疗的客观缓解率（193例患者中有60例[31%]）高于伊匹单抗单药治疗（162例患者中有21 113%1; P
Background Anti-PD-1 therapy (hereafter referred to as anti-PD-1) induces long-term disease control in approximately 30% of patients with metastatic melanoma; however, two-thirds of patients are resistant and will require further treatment. We aimed to determine the efficacy and safety of ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab) compared with ipilimuinab monotherapy in patients who are resistant to anti-PD-(L)1 therapy (hereafter referred to as anti-PD-[L]1).Methods This multicentre, retrospective, cohort study, was done at 15 melanoma centres in Australia, Europe, and the USA. We included adult patients (aged >= 18 years) with metastatic melanoma (unresectable stage III and IV), who were resistant to anti-PD-(L)1 (innate or acquired resistance) and who then received either ipilimumab monotherapy or ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab), based on availability of therapies or clinical factors determined by the physician, or both. Tumour response was assessed as per standard of care (CT or PET-CT scans every 3 months). The study endpoints were objective response rate, progression-free survival, overall survival, and safety of ipilimumab compared with ipilimumab plus anti-PD-1.Findings We included 355 patients with metastatic melanoma, resistant to anti-PD-(L)1 (nivolumab, pembrolizumab, or atezolizumab), who had been treated with ipilimumab monotherapy (n=162 [46%]) or ipilimumab plus anti-PD-1 (n=193 [54%]) between Feb 1,2011, and Feb 6, 2020. At a median follow-up of 22.1 months (IQR 9.5-30.9), the objective response rate was higher with ipilimumab plus anti-PD-1 (60 [31%] of 193 patients) than with ipilimumab monotherapy (21 113%1 of 162 patients; p