Qin Angel, Street Lindsay, Cease Kemp, Viglianti Benjamin L, Warren Edus H, Zhao Lili, Ramnath Nithya
Division of Hematology and Oncology, Department of Medicine, University of Michigan Hospital, Ann Arbor, MI.
VA Ann Arbor Healthcare System, Ann Arbor, MI.
Clin Lung Cancer. 2017 Sep;18(5):559-564. doi: 10.1016/j.cllc.2017.01.012. Epub 2017 Feb 9.
Because of the prevalence of smoking in the veteran population, non-small-cell lung cancer (NSCLC) remains a significant cause of morbidity and mortality. The objectives of our study were to evaluate the extent of durable clinical benefit (DCB) to pembrolizumab in veterans with metastatic NSCLC and to identify clinical determinants of DCB.
Prospective clinical data on veterans receiving pembrolizumab were collected. Duration of response was calculated from the first date of infusion until date of disease progression on computed tomography scans, defined according to Response Evaluation Criteria in Solid Tumors version 1.1 (CTCAE).
As of the censor date, 25 veterans consented and 24 were evaluable. The response rate was 25% (6 of 24 patients), with all achieving a partial response. Four patients received palliative radiation because of focal progression and continued to receive pembrolizumab, leading to a DCB rate of 41% (10 of 24 patients). The mean duration of response at the censor date was 12.9 months (95% confidence interval [CI], 9.9-15.9) and 2.7 months (95% CI, 1.9-4.3) for those with and without DCB, respectively. Patients without DCB had a higher pack-year smoking history (P = .007). An increase in peripheral blood absolute lymphocyte count (ALC) during therapy was seen in patients with DCB (P = .073). There were no CTCAE Grade > 3 adverse events. All immune-related adverse events occurred in patients with DCB.
Nearly half of the veterans exhibited DCB and pembrolizumab therapy was well tolerated. An increase in ALC from baseline and occurrence of autoimmune phenomena might be associated with DCB. Immunotherapy with pembrolizumab is a promising therapeutic strategy in veterans with advanced NSCLC.
由于退伍军人中吸烟率较高,非小细胞肺癌(NSCLC)仍然是发病和死亡的重要原因。我们研究的目的是评估派姆单抗对转移性NSCLC退伍军人的持久临床获益(DCB)程度,并确定DCB的临床决定因素。
收集接受派姆单抗治疗的退伍军人的前瞻性临床数据。缓解持续时间从首次输注日期计算至计算机断层扫描显示疾病进展的日期,根据实体瘤疗效评价标准第1.1版(CTCAE)进行定义。
截至审查日期,25名退伍军人同意参与研究,24名可评估。缓解率为25%(24例患者中的6例),所有患者均达到部分缓解。4例患者因局部进展接受了姑息性放疗,并继续接受派姆单抗治疗,导致DCB率为41%(24例患者中的10例)。审查日期时,有DCB和无DCB患者的平均缓解持续时间分别为12.9个月(95%置信区间[CI],9.9 - 15.9)和2.7个月(95%CI,1.9 - 4.3)。无DCB的患者有更高的吸烟包年史(P = 0.007)。DCB患者在治疗期间外周血绝对淋巴细胞计数(ALC)增加(P = 0.073)。没有CTCAE 3级以上的不良事件。所有免疫相关不良事件均发生在有DCB的患者中。
近一半的退伍军人表现出DCB,且派姆单抗治疗耐受性良好。ALC较基线增加和自身免疫现象的出现可能与DCB相关。派姆单抗免疫治疗是晚期NSCLC退伍军人中一种有前景的治疗策略。