Bauml Joshua M, Mick Rosemarie, Ciunci Christine, Aggarwal Charu, Davis Christiana, Evans Tracey, Deshpande Charuhas, Miller Linda, Patel Pooja, Alley Evan, Knepley Christina, Mutale Faith, Cohen Roger B, Langer Corey J
Abramson Cancer Center, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia.
Division of Hematology/Oncology, Lankenau Medical Center, Wynnewood, Pennsylvania.
JAMA Oncol. 2019 Sep 1;5(9):1283-1290. doi: 10.1001/jamaoncol.2019.1449.
Patients with oligometastatic non-small cell lung cancer (NSCLC) may benefit from locally ablative therapy (LAT) such as surgery or stereotactic radiotherapy. Prior studies were conducted before the advent of immunotherapy, and a strong biological rationale for the use of immunotherapy exists in a minimal residual disease state.
To evaluate whether the addition of pembrolizumab after LAT improves outcomes for patients with oligometastatic NSCLC.
DESIGN, SETTING, AND PARTICIPANTS: This single-arm phase 2 trial of pembrolizumab therapy was performed from February 1, 2015, through September 30, 2017, at an academic referral cancer center. The 51 eligible patients enrolled had oligometastatic NSCLC (≤4 metastatic sites) and had completed LAT to all known sites of disease. Data were analyzed from February 1, 2015, to August 23, 2018.
Within 4 to 12 weeks of completing LAT, patients began intravenous pembrolizumab therapy, 200 mg every 21 days, for 8 cycles, with provision to continue to 16 cycles in the absence of progressive disease or untoward toxic effects.
The 2 primary efficacy end points were progression-free survival (PFS) from the start of LAT (PFS-L), which preceded enrollment in the trial, and PFS from the start of pembrolizumab therapy (PFS-P). The study was powered for comparison with historical data on the first efficacy end point. Secondary outcomes included overall survival, safety, and quality of life as measured by the Functional Assessment of Cancer Therapy-Lung instrument.
Of 51 patients enrolled, 45 (24 men [53%]; median age, 64 years [range, 46-82 years]) received pembrolizumab. At the time of analysis, 24 patients had progressive disease or had died. Median PFS-L was 19.1 months (95% CI, 9.4-28.7 months), significantly greater than the historical median of 6.6 months (P = .005). Median PFS-P was 18.7 months (95% CI, 10.1-27.1 months). Eleven patients died. Overall mean (SE) survival rate at 12 months was 90.9% (4.3%); at 24 months, 77.5% (6.7%). Neither programmed death ligand 1 expression nor CD8 T-cell tumor infiltration was associated with PFS-L. Pembrolizumab after LAT yielded no new safety signals and no reduction in quality of life.
Pembrolizumab after LAT for oligometastatic NSCLC appears to improve PFS with no reduction in quality of life.
ClinicalTrials.gov identifier: NCT02316002.
寡转移非小细胞肺癌（NSCLC）患者可能从手术或立体定向放射治疗等局部消融治疗（LAT）中获益。先前的研究是在免疫疗法出现之前进行的，而在微小残留病状态下使用免疫疗法存在强有力的生物学依据。
评估LAT后加用帕博利珠单抗是否能改善寡转移NSCLC患者的预后。
设计、地点和参与者：这项帕博利珠单抗治疗的单臂2期试验于2015年2月1日至2017年9月30日在一家学术转诊癌症中心进行。入组的51例合格患者患有寡转移NSCLC（转移部位≤4个），且已对所有已知疾病部位完成LAT。对2015年2月1日至2018年8月23日的数据进行了分析。
在完成LAT的4至12周内，患者开始静脉注射帕博利珠单抗治疗，每21天200mg，共8个周期，若无疾病进展或不良毒性作用，可继续至16个周期。
2个主要疗效终点为从LAT开始（LAT-PFS，先于试验入组）的无进展生存期（PFS）和从帕博利珠单抗治疗开始（PFS-P）的PFS。该研究的效能用于与首个疗效终点的历史数据进行比较。次要结局包括总生存期、安全性以及通过癌症治疗-肺部功能评估工具测量的生活质量。
51例入组患者中，45例（24例男性[53%]；中位年龄64岁[范围46 - 82岁]）接受了帕博利珠单抗治疗。在分析时，24例患者出现疾病进展或死亡。中位LAT-PFS为19.1个月（95%CI，9.4 - 28.7个月），显著长于历史中位值6.6个月（P = 0.005）。中位PFS-P为18.7个月（95%CI，10.1 - 27.1个月）。11例患者死亡。12个月时总体平均（SE）生存率为90.9%（4.3%）；24个月时为77.5%（6.7%）。程序性死亡配体1表达和CD8 T细胞肿瘤浸润均与LAT-PFS无关。LAT后使用帕博利珠单抗未产生新的安全信号，生活质量也未降低。
LAT后使用帕博利珠单抗治疗寡转移NSCLC似乎可改善PFS，且不降低生活质量。
ClinicalTrials.gov标识符：NCT02316002。
