Prospective randomized phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer - results of the SUNNIFORECAST trial.

Tyrosine kinase inhibitors with or without immune checkpoint inhibition are considered as a standard of care (SOC), but optimal treatment is not yet defined.

酪氨酸激酶抑制剂，无论是单独使用还是与免疫检查点抑制剂联合使用，都被认为是标准治疗（SOC），但最佳治疗方案尚未明确。

We designed the first prospective randomized trial comparing ipilimumab/nivolumab to SOC.

我们设计了首个前瞻性随机试验，比较了伊匹木单抗/纳武利尤单抗与标准治疗方案(SOC)。

patients_and_methods

We randomized adult patients with previously untreated advanced or metastatic nccRCC 1:1 to nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by fixed dose nivolumab of 240 mg every 2 weeks or 480 mg every 4 weeks or to SOC.

我们将既往未接受治疗的成年晚期或转移性非典型肾细胞癌(nccRCC)患者按1:1的比例随机分为两组，一组接受每3周一次的纳武利尤单抗3 mg/kg联合伊匹木单抗1 mg/kg，共4剂，随后每2周一次固定剂量的纳武利尤单抗240 mg或每4周一次480 mg；另一组接受标准治疗方案(SOC)。

Patients were stratified by histology and by IMDC risk score.

患者根据组织学和IMDC风险评分进行分层。

Central pathology review was mandatory.

中央病理审查是强制性的。

The primary endpoint was the overall survival(OS) rate at 12 months, secondary endpoints included median OS, response rate, progression-free survival(PFS), safety and quality of life.

主要终点是12个月的总生存（OS）率，次要终点包括中位总生存期、反应率、无进展生存期（PFS）、安全性和生活质量。

Results

In total, 157 patients were assigned to receive ipilimumab/nivolumab, and 152 to SOC.

共有157名患者被分配接受伊匹木单抗/纳武利尤单抗治疗，152名患者接受标准治疗。

The 12-month survival rate was 78% with ipilimumab/nivolumab [95% confidence interval(CI) 71-84%] compared to 68% with SOC (95% CI 60-75%, P = 0.026).

12个月生存率为78%的患者接受了伊匹木单抗/纳武利尤单抗治疗[95%置信区间(CI) 71-84%]，而接受标准治疗(SOC)的患者为68%[95%置信区间(CI) 60-75%，P = 0.026]。

Median OS was 33.2 months versus 25.2 months, P = 0.163 [HR 0.81 (0.61-1.099)].

中位总生存期为33.2个月对比25.2个月，P = 0.163 [风险比HR 0.81 (0.61-1.099)]。

PFS was similar in both arms [HR 0.99 (0.77-1.28)].

两组的无进展生存期相似[风险比 0.99 (0.77-1.28)].

The ORR was 32.8% versus 19.3%.

客观缓解率分别为32.8%和19.3%.

No major differences between papillary and non-papillary RCC subtypes were observed for any endpoint.

在任何终点指标上，乳头状和非乳头状肾细胞癌亚型之间未观察到主要差异。

Exploratory analysis showed a significant OS advantage [HR 0.56 (95% CI 0.37-0.86)] associated with a PD-L1 CPS score ≥1.

探索性分析显示，PD-L1 CPS评分≥1与显著的总生存优势相关[HR 0.56 (95% CI 0.37-0.86)]。

Treatment discontinuation due to toxicity occurred in 27 patients (17%) with ipilimumab/nivolumab and 13 patients (9%) with SOC.

因毒性反应导致治疗中断的患者有27名（17%）使用伊匹木单抗/纳武利尤单抗，13名（9%）使用标准治疗（SOC）治疗。

Conclusions

Ipilimumab/nivolumab demonstrated a significantly longer OS at the 12-month milestone and an acceptable toxicity profile.

伊匹木单抗/纳武利尤单抗在12个月里程碑处显示出显著更长的总生存期（OS）和可接受的毒性反应特征。

Our results therefore underline a relevant clinical benefit of ipilimumab/nivolumab in previously untreated nccRCC entities compared to current SOC.

因此，我们的结果强调了在未经治疗的nccRCC实体中，与当前标准治疗相比，伊匹木单抗/纳武利尤单抗具有显著的临床益处。