Objectives

Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC), who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy.

Materials and methods

CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression. Patients were randomized to canakinumab plus docetaxel or placebo plus docetaxel.

Results

A total of 237 patients were randomly allocated: 120 (51 %) to canakinumab and 117 (49 %) to placebo, stratified by histology and prior lines of therapy. Three patients in the placebo arm did not receive study treatment. The trial did not meet its primary endpoint of overall survival: median 10.5 months (95 % confidence interval [CI], 8.1–12.4) for the canakinumab arm and 11.3 months (95 % CI, 8.5–13.8) for the placebo arm (hazard ratio, 1.06 [95 % CI, 0.76–1.48]; one-sided P-value = 0.633). AEs (any grade) were reported in 95 % of patients in the canakinumab group and in 98 % of patients in the placebo group. Grade 3–4 AEs were experienced by 62 % and 64 % of patients in the canakinumab and placebo groups, respectively, and grade 5 AEs were experienced by 8 % and 5 %. Prespecified, post-hoc, subgroup analyses showed that patients with undetected circulating tumor DNA (ctDNA) and/or lower levels (<10 mg/L) of C-reactive protein (CRP) achieved longer progression-free and overall survival than those with detected ctDNA or higher (≥10 mg/L) CRP levels. There was no association with treatment arm.

Conclusion

Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy.

Clinical registration: NCT03626545.

中文翻译：

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卡那奴单抗联合多西他赛与单用多西他赛治疗铂类双药化疗和免疫治疗后晚期非小细胞肺癌的比较 (CANOPY-2)：多中心、随机、双盲 3 期试验

目标

Canakinumab 是一种白细胞介素 1 β 抑制剂，之前显示出可降低肺癌发病率和死亡率 (CANTOS)。在这里，我们比较了卡那奴单抗与安慰剂在晚期非小细胞肺癌 (NSCLC) 患者中的疗效/安全性，这些患者在铂类双重化疗 (PDC) 和免疫治疗后病情出现进展。

材料和方法

CANOPY-2 是一项随机、双盲、3 期试验，纳入了 IIIB/IV 期 NSCLC 成年患者，无EGFR或ALK改变，这些患者之前接受过一种 PDC 治疗方案和一种先前的程序性死亡 1/程序性死亡配体1抑制剂并经历了随后的疾病进展。患者被随机分配至卡那奴单抗加多西他赛组或安慰剂加多西他赛组。

结果

共有 237 名患者被随机分配：120 名患者（51%）接受卡那单抗治疗，117 名患者（49%）接受安慰剂治疗，按组织学和既往治疗方案进行分层。安慰剂组的三名患者没有接受研究治疗。该试验未达到总生存期的主要终点：卡那奴单抗组的中位生存期为 10.5 个月（95% 置信区间 [CI]，8.1–12.4），安慰剂组的中位生存期为 11.3 个月（95% CI，8.5–13.8）（风险）比率，1.06 [95% CI，0.76–1.48]；单侧P值 = 0.633）。卡那奴单抗组 95% 的患者和安慰剂组 98% 的患者报告了 AE（任何级别）。卡那奴单抗组和安慰剂组中分别有 62% 和 64% 的患者经历过 3-4 级 AE，而 8% 和 5% 的患者经历过 5 级 AE。预先指定的事后亚组分析显示，与未检测到循环肿瘤 DNA (ctDNA) 和/或 C 反应蛋白 (CRP) 水平较低 (<10 mg/L) 的患者相比，未检测到循环肿瘤 DNA (ctDNA) 的患者获得了更长的无进展生存期和总生存期。检测到 ctDNA 或更高 (≥10 mg/L) CRP 水平。与治疗组没有关联。

结论

在多西他赛中添加卡那单抗并没有为 PDC 和免疫治疗后进展的晚期 NSCLC 患者提供额外的益处。

临床注册： NCT03626545。