背景：Camrelizumab聯合吉西他濱和順鉑（GP）在1期試驗中顯示，作為複發或轉移性鼻咽癌（R/M NPC）患者（PT）的一線（1L）治療具有良好的初步抗癌活性（W Fang等人；柳葉刀Oncol 2018）。在這裏，我們在3期試驗中比較了camrelizumab與安慰劑加GP作為1L治療R/M NPC患者的療效和安全性。
Background: Camrelizumab plus gemcitabine and cisplatin (GP) showed promising preliminary anticancer activity as first line (1L) therapy in patients (pts) with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) in a phase 1 trial (W Fang et al; Lancet Oncol 2018). Here, we compared the efficacy and safety of camrelizumab with placebo plus GP as 1L therapy for pts with R/M NPC in a phase 3 trial.
方法：符合條件的R/M NPC患者隨機（1:1）接受camrelizumab（200mg，第1天）加吉西他濱（1000mg/m2，第1天，第8天）和順鉑（80mg/m2，第1天）或安慰劑加相同化療方案Q3W靜脈注射，最多6個周期，隨後用camrelizumab或安慰劑進行維持治療。主要終點是獨立評審委員會（IRC）的無進展生存率（PFS）。次要終點包括研究者評估的PFS、客觀緩解率（ORR）、疾病控製率（DCR）、緩解持續時間（DOR）、總生存期（OS）和耐受性。
Methods: Eligible pts with previously untreated R/M NPC were randomized (1:1) to receive either camrelizumab (200 mg on day 1) plus gemcitabine (1000 mg/m2 on days 1, 8) and cisplatin (80 mg/m2 on day 1) or placebo plus the same chemotherapy regimens intravenously Q3W for a maximum of 6 cycles, followed by maintenance therapy with camrelizumab or placebo. The primary end point was progression-free survival (PFS) per independent review committee (IRC). Secondary end points included investigator-assessed PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) and tolerability.
結果：從2018年11月到2019年11月，來自28個中心的263名患者被隨機分為camrelizumab加GP組（n=134，camrelizumab組）或安慰劑加GP組（n=129，安慰劑組）。在2020年12月31日（67.7%到期日）數據截止時，發生178例IRC評估的PFS事件，中位隨訪時間為15.6個月（範圍1.3-25.5）。在camrelizumab組，每個IRC的PFS中位數為10.8個月（95%CI 8.5-13.6），安慰劑組為6.9個月（95%CI 5.9-7.9）（HR 0.51[95%CI 0.37-0.69]；單側P<0.0001）。研究者評估的PFS顯示了類似的結果。IRC評估的ORR在camrelizumab組為88.1%（95%CI 81.3-93.0），安慰劑組為80.6%（95%CI 72.7-87.1），DOR中位數為9.9（95%CI 7.7-12.5）和5.7個月（95%CI 5.2-6.9）；心率分別為0.48[95%可信區間0.34-0.68]）。camrelizumab組的DCR為96.3%（95%CI 91.5-98.8），安慰劑組為94.6%（95%CI 89.1-97.8）。18個月PFS發生率分別為34.8%（95%ci25.7-44.1）和12.7%（95%ci6.8-20.5）。在camrelizumab組和安慰劑組中觀察到OS獲益（中位數未達到vs 22.6個月；心率0.67[95%可信區間0.41-1.11]）。等級≥3治療相關的不良事件（TRAEs）發生在93%的患者中，卡美瑞珠單抗組和90%的安慰劑組。最普通的等級≥白細胞計數下降（66%vs70%），中性粒細胞計數下降（64%vs65%），血小板計數下降（40%vs40%），貧血（39%vs43%）。這些差異無統計學意義。安全狀況如預期，沒有觀察到新的信號。
結果：從2018年11月到2019年11月，來自28個中心的263名患者被隨機分為camrelizumab加GP組（n=134，camrelizumab組）或安慰劑加GP組（n=129，安慰劑組）。在2020年12月31日（67.7%到期日）數據截止時，發生178例IRC評估的PFS事件，中位隨訪時間為15.6個月（範圍1.3-25.5）。在camrelizumab組，每個IRC的PFS中位數為10.8個月（95%CI 8.5-13.6），安慰劑組為6.9個月（95%CI 5.9-7.9）（HR 0.51[95%CI 0.37-0.69]；單側P<0.0001）。研究者評估的PFS顯示了類似的結果。IRC評估的ORR在camrelizumab組為88.1%（95%CI 81.3-93.0），安慰劑組為80.6%（95%CI 72.7-87.1），DOR中位數為9.9（95%CI 7.7-12.5）和5.7個月（95%CI 5.2-6.9）；心率分別為0.48[95%可信區間0.34-0.68]）。camrelizumab組的DCR為96.3%（95%CI 91.5-98.8），安慰劑組為94.6%（95%CI 89.1-97.8）。18個月PFS發生率分別為34.8%（95%ci25.7-44.1）和12.7%（95%ci6.8-20.5）。在camrelizumab組和安慰劑組中觀察到OS獲益（中位數未達到vs 22.6個月；心率0.67[95%可信區間0.41-1.11]）。等級≥3治療相關的不良事件（TRAEs）發生在93%的患者中，卡美瑞珠單抗組和90%的安慰劑組。最普通的等級≥白細胞計數下降（66%vs70%），中性粒細胞計數下降（64%vs65%），血小板計數下降（40%vs40%），貧血（39%vs43%）。這些差異無統計學意義。安全狀況如預期，沒有觀察到新的信號。
Results: From Nov 2018 to Nov 2019, 263 pts from 28 centers were randomized to camrelizumab plus GP (n = 134, camrelizumab arm) or placebo plus GP (n = 129, placebo arm). At data cutoff on Dec 31, 2020 (67.7% maturity), 178 IRC-assessed PFS events occurred, and the median follow-up was 15.6 months (range 1.3-25.5). The median PFS per IRC was 10.8 months (95% CI 8.5-13.6) in the camrelizumab arm and 6.9 (95% CI 5.9-7.9) in the placebo arm (HR 0.51 [95% CI 0.37-0.69]; one-sided P< 0.0001). Investigator-assessed PFS showed similar results. IRC-assessed ORR was 88.1% (95% CI 81.3-93.0) in the camrelizumab arm and 80.6% (95% CI 72.7-87.1) in the placebo arm, with a median DOR of 9.9 (95% CI 7.7-12.5) and 5.7 months (95% CI 5.2-6.9; HR 0.48 [95% CI 0.34-0.68]), respectively. The DCR was 96.3% (95% CI 91.5-98.8) in the camrelizumab arm and 94.6% (95% CI 89.1-97.8) in the placebo arm. 18-month PFS rate was 34.8% (95% CI 25.7-44.1) vs 12.7% (95% CI 6.8-20.5), respectively. OS benefit was observed in the camrelizumab arm vs placebo arm (median not reached vs 22.6 months; HR 0.67 [95% CI 0.41-1.11]). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 93% of pts in the camrelizumab arm and 90% in the placebo arm. The most common grade ≥3 TRAEs were decreased white blood cell count (66% vs 70%), decreased neutrophil count (64% vs 65%), decreased platelet count (40% vs 40%), and anemia (39% vs 43%). None of the differences were statistically significant. The safety profile was as expected, with no new signals observed.
結論:卡瑞利珠單抗+GP 化療方案一線治療 R/M NPC 顯著延長了 PFS，安全性可控。此數據表明卡瑞利珠單抗 +GP 可能是 R/M NPC 一線治療的標準。
Conclusions: Addition of camrelizumab to GP significantly prolonged PFS as 1L therapy for R/M NPC, with a manageable safety profile. These data suggest that first line treatment with camrelizumab plus GP could be a standard of care for R/M NPC.
