ESMO 2023大咖点评丨刘云鹏教授：“去化疗”纳武利尤单抗联合伊匹木单抗在MSI-H胃/食管胃结合部癌患者中表现出显著的疗效

23-11-07 肿瘤瞭望

编者按：欧洲肿瘤内科学会（ESMO）年会已于今日在西班牙马德里开幕。《肿瘤瞭望》选取ESMO 2023报道的重要研究，邀请国内大咖专家予以点评。中国医科大学第一医院刘云鹏教授针对NO LIMIT研究纳武利尤单抗联合低剂量伊匹木单抗的去化疗方案治疗MSI-H胃癌的数据分享见解和思考。

1513MO - 纳武利尤单抗联合低剂量伊匹木单抗作为晚期胃或食管胃结合部MSI-H肿瘤患者一线治疗的II期研究：NO LIMIT研究的初步结果（WJOG13320G/CA209-7W7）

▌背景

微卫星高度不稳定（MSI-H）是免疫检查点抑制剂治疗有效的既定生物标志物。在此，我们报告了在一项II期研究中，纳武利尤单抗联合低剂量伊匹木单抗一线治疗MSI-H晚期胃癌或食管胃结合部癌（GC）患者的有效性和安全性。

▌方法

符合条件的患者为不可切除的晚期、复发或转移性胃癌，组织学确诊为腺癌，使用MSI-IVD试剂盒（FALCO）确诊为MSI-H状态，既往未接受过系统性抗癌治疗作为晚期或转移性疾病的主要治疗。每两周给予纳武利尤单抗（240 mg），每六周给予伊匹木单抗（1 mg/kg），直到疾病进展或不可耐受的毒性。主要终点是通过盲法独立中心审查（BICR）的客观缓解率（ORR）。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）、反应持续时间（DOR）、总生存期（OS）和安全性。

▌结果

在2020年11月至2022年8月期间，从935例筛查病例中纳入了29例患者。中位年龄75岁（54-84岁），44.8%的患者为男性。在数据截止日期（2022年12月12日），3例和15例患者分别获得了确认的完全缓解和部分缓解，ORR为62.1% (95%CI: 42.3-79.3)。DCR为79.3% (95%CI：60.3-92.0)。中位随访9.0个月（范围4.0-18.0），中位PFS为13.8个月（95%CI：13.7-NR），中位DOR和OS尚未达到。12个月的PFS和OS率分别为73%（95%CI：52-86）和80%(95%CI：57-91)。中断治疗最常见的原因是不良事件。安全谱与已知的纳武利尤单抗+低剂量伊匹木单抗的安全谱一致，没有额外的安全性事件。未观察到治疗相关死亡。

▌结论

纳武利尤单抗联合低剂量伊匹木单抗的去化疗方案在MSI-H GC患者中表现出显著的疗效和良好的耐受性。

刘云鹏教授点评

晚期胃癌除少数Her-2阳性病人之外，无论微卫星状态如何，只能采用化疗，但mPFS只有6-8个月，mOS只有10-13个月，预后很差。

免疫检查点抑制剂对包括胃癌在内的多种MSI-H型肿瘤显示了喜人的疗效。为进一步提高免疫治疗的效果，NO LIMIT研究采用纳武利尤单抗联合低剂量伊匹木单抗方案一线治疗MSI-H型晚期胃癌或食管胃结合部癌。结果显示，mPFS达到13.8个月，mOS尚未达到，并且安全性良好。

双免联合可以显著提高疗效，但毒性是重要的限制因素。NO LIMIT研究的联合模式有可能为MSI-H型晚期胃癌的治疗带来突破，并改变晚期胃癌的药物治疗格局，值得期待。

摘要原文

1513MO - A phase II study of nivolumab plus low dose ipilimumab as first -line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209-7W7)

Background：Microsatellite instability-high (MSI-H) is an established biomarker for response to immune checkpoint inhibitors. Herein, we report the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line therapy in MSI-H advanced gastric or esophagogastric junction cancer (GC) patients from the phase II study.

Methods：Eligible patients were unresectable advanced, recurrent, or metastatic GC with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Nivolumab (240 mg) biweekly and ipilimumab (1 mg/kg) every six weeks were given until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety.

Results：Between November 2020 and Aug 2022, 29 patients were enrolled from 935 screened cases. The median age was 75 (range 54-84), and 44.8% of patients were male. At the data cut-off (December 12, 2022), 3 and 15 patients achieved confirmed complete and partial responses with ORR of 62.1% (95% CI: 42.3-79.3). The DCR was 79.3% (95% CI, 60.3-92.0). With the median follow-up of 9.0 months (range, 4.0-18.0), the median PFS was 13.8 (95% CI, 13.7-NR) months, and median DOR and OS were not reached yet. 12-month PFS and OS rates yielded 73% (95% CI, 52-86) and 80% (95% CI, 57-91), respectively. The most common reason for treatment discontinuation was adverse events. The safety profile was consistent with the known profiles of nivolumab plus low dose ipilimumab, and there were no unexpected safety signals. Treatment-related death was not observed.

Conclusions：The chemo-free strategy with a combination of nivolumab and low-dose ipilimumab demonstrated high and robust efficacy with good tolerability in MSI-H GC patients.

Clinical trial identification：jRCT2080225304.

https://cslide.ctimeetingtech.com/esmo2023/attendee/confcal/session/list?q=1513MO