Dagogo-Jack Ibiayi, Lanfranchi Michael, Gainor Justin F, Giobbie-Hurder Anita, Lawrence Donald P, Shaw Alice T, Sullivan Ryan J
*Massachusetts General Hospital Cancer Center †Department of Radiology, Massachusetts General Hospital, Harvard Medical School ‡Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
J Immunother. 2017 Apr;40(3):108-113. doi: 10.1097/CJI.0000000000000159.
A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab. Twenty-six (72%) patients with BM had received prior treatment for BM. With median follow-up of 17.2 months, 54 patients (61%) developed progressive disease on pembrolizumab. Intracranial progression occurred in 19 patients (21%), 3 of whom did not have BM before treatment. Median time to progression at any site was 6 months for those without BM (n=53), 5 months for those with treated BM (n=26), and 1.2 months for patients with untreated BM (n=10). Using a Cox regression model adjusted for baseline factors, there was a statistically significant (Wald χ P=0.003) reduction in the hazard of progression for patients without BM [hazard ratio, 0.19; 90% confidence interval, 0.08-0.42) and patients with treated BM (hazard ratio, 0.27; 90% confidence interval, 0.12-0.64) compared with those with untreated BM. In conclusion, melanoma patients with pretreated BM can have durable systemic responses to pembrolizumab. Large, prospective studies are needed to evaluate the intracranial antitumor activity of pembrolizumab in melanoma patients with untreated BM.
总计50%的黑色素瘤患者会发生脑转移（BM）。帕博利珠单抗基于显著的全身抗肿瘤活性被批准用于治疗转移性黑色素瘤。由于帕博利珠单抗试验中脑转移患者入组率低，其对黑色素瘤脑转移的疗效仍不清楚。我们回顾了2014年5月1日至2015年10月31日期间在我们机构接受帕博利珠单抗治疗的89例连续黑色素瘤患者的记录，以确定疾病进展时间。36例（40%）患者在使用帕博利珠单抗前已有脑转移。26例（72%）有脑转移的患者曾接受过脑转移的先前治疗。中位随访17.2个月时，54例（61%）患者在使用帕博利珠单抗治疗期间出现疾病进展。19例（21%）患者发生颅内进展，其中3例在治疗前没有脑转移。无脑转移患者（n = 53）任何部位的中位疾病进展时间为6个月，接受过治疗的脑转移患者（n = 26）为5个月，未接受治疗的脑转移患者（n = 10）为1.2个月。使用针对基线因素进行调整的Cox回归模型，与未接受治疗的脑转移患者相比，无脑转移患者[风险比，0.19；90%置信区间，0.08 - 0.42]和接受过治疗的脑转移患者（风险比，0.27；90%置信区间，0.12 - 0.64）的疾病进展风险有统计学显著降低（Wald χ P = 0.003）。总之，先前接受过治疗的脑转移黑色素瘤患者对帕博利珠单抗可产生持久的全身反应。需要开展大型前瞻性研究来评估帕博利珠单抗在未接受治疗的脑转移黑色素瘤患者中的颅内抗肿瘤活性。
