纳武利尤单抗联合多西他赛用于未经化疗的转移性去势抵抗性前列腺癌患者：II期CheckMate 9KD试验结果
Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial.
作者信息
Fizazi Karim, González Mella Pablo, Castellano Daniel, Minatta Jose N, Rezazadeh Kalebasty Arash, Shaffer David, Vázquez Limón Juan C, Sánchez López Héctor M, Armstrong Andrew J, Horvath Lisa, Bastos Diogo A, Amin Neha P, Li Jia, Unsal-Kacmaz Keziban, Retz Margitta, Saad Fred, Petrylak Daniel P, Pachynski Russell K
机构信息
Department of Cancer Medicine, Gustave Roussy, University Paris Saclay, Villejuif, France.
Department of Radiotherapy, Fundación Arturo López Pérez, Santiago, Chile.
出版信息
Eur J Cancer. 2022 Jan;160:61-71. doi: 10.1016/j.ejca.2021.09.043. Epub 2021 Nov 18.
BACKGROUND
Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC).
METHODS
In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA-RR; ≥50% decrease from baseline).
RESULTS
The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7-55.7), and the confirmed PSA-RR (95% CI) was 46.9% (35.7-58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0-11.6) and 18.2 (14.6-20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3-4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel).
CONCLUSIONS
Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. CLINICALTRIALS.
GOV REGISTRATION
NCT03338790.
背景
多西他赛具有免疫刺激作用，可能促进免疫反应性前列腺肿瘤微环境，为与纳武利尤单抗（程序性死亡-1抑制剂）联合用于转移性去势抵抗性前列腺癌（mCRPC）提供了理论依据。
方法
在非随机、多队列、全球II期CheckMate 9KD试验中，84例未接受过化疗的mCRPC患者，正在接受雄激素剥夺治疗且既往接受过≤2种新型激素疗法（NHTs），每3周接受一次纳武利尤单抗360 mg和多西他赛75 mg/m²，同时每日两次服用泼尼松5 mg（≤10个周期），然后每4周接受一次纳武利尤单抗480 mg（≤2年）。共同主要终点为客观缓解率（ORR）和前列腺特异性抗原缓解率（PSA-RR；较基线下降≥50%）。
结果
确认的ORR（95%置信区间[CI]）为40.0%（25.7 - 55.7），确认的PSA-RR（95% CI）为46.9%（35.7 - 58.3）。中位（95% CI）影像学无进展生存期（rPFS）和总生存期（OS）分别为9.0（8.0 - 11.6）个月和18.2（14.6 - 20.7）个月。在既往接受过与未接受过NHT的亚组中，ORR分别为38.7%和42.9%，PSA-RR分别为39.6%和60.7%，中位rPFS分别为8.5个月和12.0个月，中位OS分别为16.2个月和未达到。同源重组缺陷状态或肿瘤突变负荷似乎不影响疗效。最常见的任何级别和3 - 4级治疗相关不良事件分别为疲劳（39.3%）和中性粒细胞减少（16.7%）。发生了3例治疗相关死亡（1例与纳武利尤单抗相关的肺炎；2例与多西他赛相关的肺炎）。
结论
纳武利尤单抗联合多西他赛对未接受过化疗的mCRPC患者具有临床活性。安全性与各组分一致。这些结果支持在正在进行的III期CheckMate
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