Aboudaram Amélie, Modesto Anouchka, Chaltiel Léonor, Gomez-Roca Carlos, Boulinguez Serge, Sibaud Vincent, Delord Jean-Pierre, Chira Ciprian, Delannes Martine, Moyal Elizabeth, Meyer Nicolas
Departments of aRadiation OncologybBiostatistics, Claudius Regaud InstitutecDepartment of Medical OncologydDepartment of Dermatology, Toulouse University Hospital, Larrey Hospital, The Toulouse University Institute of Cancer, Toulouse, France.
Melanoma Res. 2017 Oct;27(5):485-491. doi: 10.1097/CMR.0000000000000386.
A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4.3) were compared between patients receiving concurrent RT (IR) or no irradiation (NIR). Fifty-nine patients received anti-PD-1 immunotherapy [pembrolizumab (n=28) or nivolumab (n=31)] between August 2014 and December 2015 at our institution. Among these, 29% (n=17) received palliative RT for a total of 21 sites, with a mean dose of 30 Gy delivered in 10 fractions. Acute and late toxicity profiles were similar in the two groups. After a 10-month median follow-up, the objective response rate (complete or partial response) was significantly higher in the IR group versus the NIR group (64.7 vs. 33.3%, P=0.02) and one complete responder after RT was compatible with an abscopal effect. The 6-month disease-free survival and overall survival rates for the NIR group versus the IR group were 49.7 versus 64.7% (P=0.32) and 58.8 versus 76.4% (P=0.42), respectively. We report here that the combination of RT and anti-PD-1 immunotherapy is well tolerated and leads to a significant higher tumor response rate within and outside the irradiated field, which is emphasized by the first reported case of an abscopal effect in solid tumors.
免疫检查点抑制剂与放射治疗（RT）联合使用是一种很有前景的治疗策略，部分是由远隔效应介导的，但关于这种联合治疗的临床经验仍然很少。我们回顾性收集了所有连续的转移性黑色素瘤患者接受程序性死亡1（PD-1）免疫检查点抑制剂治疗的临床数据和治疗模式。比较了接受同步放疗（IR）或未接受放疗（NIR）的患者的生存数据、最佳总体反应以及急性和迟发性毒性（根据不良事件通用术语标准v 4.3分级）。2014年8月至2015年12月期间，我们机构有59例患者接受了抗PD-1免疫治疗[帕博利珠单抗（n = 28）或纳武利尤单抗（n = 31）]。其中，29%（n = 17）接受了姑息性放疗，共21个部位，平均剂量为30 Gy，分10次给予。两组的急性和晚期毒性特征相似。经过10个月的中位随访，IR组的客观缓解率（完全或部分缓解）显著高于NIR组（64.7%对33.3%，P = 0.02），放疗后有1例完全缓解者符合远隔效应。NIR组与IR组的6个月无病生存率和总生存率分别为49.7%对64.7%（P = 0.32）和58.8%对76.4%（P = 0.42）。我们在此报告，放疗与抗PD-1免疫治疗联合使用耐受性良好，可使照射野内外的肿瘤反应率显著提高，实体瘤中首例远隔效应的报道就突出了这一点。
