Introduction

Papillary renal cell carcinoma (PRCC) represents 10%–15% of renal carcinomas. No standard treatments exist for metastatic PRCC (mPRCC) patients. Axitinib is indicated as second-line treatment in metastatic clear cell renal carcinoma, and we aim to assess the efficacy of this vascular endothelial growth factor receptor inhibitor in front line for mPRCC.

Methods

This French multicentre phase II study AXIPAP enrolled untreated mPRCC patients, with measurable disease, Eastern Cooperative Oncology Group performance status ≤ 1 and adequate organ functions. PRCC had to be confirmed by histology expert central review. Axitinib was administered orally 5 mg twice daily. Primary end-point was progression-free rate at 24 weeks (24w-PFR) by central review.

Results

Fifty-six patients were screened, and 44 included (13 type 1, 30 type 2 and 1 non-specified). The median follow-up was 32.0 (13.1–39.9) months. The 24w-PFR was 45.2% (95% confidence interval [CI], 32.6% to +∞), the objective response rate was 28.6% (95% CI, 15.7%–44.6%) (type 1: 7.7%; type 2: 35.7%). The overall median progression free survival was 6.6 months (95% CI, 5.5–9.2), 6.7 months (95% CI, 5.5–9.2) and 6.2 months (95% CI, 5.4–9.2) for type 1 and 2, respectively. Median overall survival was 18.9 months (95% CI, 12.8–not reached). Adverse events were as expected; grade 3–4 treatment-related adverse events were rare except hypertension (27%).

Conclusions

Axitinib demonstrated encouraging efficacy in mPRCC patients, especially in type 2 PRCC. Toxicity was manageable. Axitinib appears as an interesting option for first-line treatment and to be worth further investigation in combination with immunotherapy in these patients. Expert pathology review should be recommended in this setting.

Clinical trial registration

ClinicalTrials.gov, NCT02489695.

中文翻译：

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阿昔替尼用于转移性乳头状肾细胞癌患者的一线治疗：多中心，开放标签，单臂，II期AXIPAP试验的结果

介绍

乳头状肾细胞癌（PRCC）占肾癌的10％–15％。对于转移性PRCC（mPRCC）患者，尚无标准疗法。阿昔替尼被指定为转移性透明细胞肾癌的二线治疗，我们的目标是评估这种血管内皮生长因子受体抑制剂在mPRCC一线的疗效。

方法

这项法国的多中心II期临床研究AXIPAP招募了未经治疗的mPRCC患者，这些患者可测量的疾病，东部合作肿瘤小组的工作状态≤1且器官功能良好。PRCC必须由组织学专家中央审查确认。阿昔替尼每天两次口服5 mg。主要终点为中心评估的24周无进展率（24w-PFR）。

结果

筛选了56例患者，其中包括44例（13例1型，30例2型和1例未指定）。中位随访时间为32.0（13.1–39.9）个月。24w-PFR为45.2％（95％置信区间[CI]，32.6％至+∞），客观缓解率为28.6％（95％CI，15.7％–44.6％）（类型1：7.7％；类型2 ：35.7％）。1型和2型患者的总中位数无进展生存期分别为6.6个月（95％CI，5.5-9.2），6.7个月（95％CI，5.5-9.2）和6.2个月（95％CI，5.4-9.2）。中位总生存期为18.9个月（95％CI，12.8-未达到）。不良事件符合预期；除高血压（27％）外，罕见的3-4级治疗相关不良事件。

结论

阿昔替尼在mPRCC患者中表现出令人鼓舞的疗效，尤其是在2型PRCC中。毒性是可控的。阿昔替尼似乎是一线治疗的有趣选择，值得在这些患者中结合免疫疗法进行进一步研究。在这种情况下，建议进行专家病理学检查。

临床试验注册

ClinicalTrials.gov，NCT02489695。