根据缓解率以及中位 PFS的结果, Avastin确 保了未来卵巢癌复发治疗的相关研究 Avastin 15mg/kg q3w对于既往接受过 1~2次化疗方案的卵巢癌患者耐受性良好
副反应都在预料之中，且大多比较轻微，容易控 制
许多患者接受了 >30 个周期的治疗

Burger, et al. JCO 2007
*Assessed using RECIST criteria ‡14 of 32 patients with stable disease had PFS >6 months
Avastin (n=62) 21 (13–31) 3(2) 52(32) 40 (30–54) 4.7 16.9
Data for the primary efficacy endpoints are shown in bold Burger, et al. JCO 2007
CP = carboplatin/paclitaxel; PLD = pegylated liposomal doxorubicin; NR = not reported; NRe = not reached
1. Burger, et al. JCO 2007; 2. Cannistra, et al. JCO 2007; 3. Smerdal, et al. ESMO 2009; 4. Garcia, et al. JCO 2008 5. McGonigle, et al. ASCO 2008; 6. Kikuchi, et al. ASCO 2009; 7. Muggia, et al. ASCO 2009; 8. Nimeiri, et al. Gynecol Oncol 2008 9. Parmar, et al. Lancet 2003; 10. Pfisterer, et al. JCO 2006; 11. Pujade-Lauraine, et al. ASCO 2009; 12. Mutch, et al. JCO 2007 13. Ferrandina, et al. JCO 2007; 14. Gordon, et al. JCO 2001
Study therapy Avastin Avastin Avastin Avastin + cyclophosphamide Avastin + topotecan Avastin + PLD Avastin + PLD Avastin + erlotinib
OR (%) 21 16 30 24 22 36 15
2 No. of platinum regimens (%) 1 2 Platinum-free interval <6 months (%)
EOC = epithelial ovarian cancer; PPC = primary peritoneal cancer Burger, et al. JCO 2007
Study Prior regimens, median (range) Events, n (%)
1
Micha, et al.2
Penson, et al.3 Burger, et al. (GOG-170D)4 Muggia, et al.5 Kikuchi, et al.6 Garcia, et al.7 Nimeiri, et al.8 Cannistra, et al.9 Bidus, et al.10 Wright, et al.11 Smerdel, et al.12 Monk, et al.13 Wright, et al.14 Total
Avastin-based combination regimens
NR 4.1 5.8–13.0 3.1–4.6
NR 11 17.3–29.0 9.5–13.5
Representative historical trials Platinum ± paclitaxel, 31–47 gemcitabine or PLD Topotecan, gemcitabine 6–29 or PLD
GOG 170D: Avastin单药治疗卵巢癌复发的 II 期临床试验– 安全性
没有发现新发或预期以外的毒性发生，3/4 不良事件的发生率与其他肿瘤类型一 致
12 10 Patients (%) 8 6 4 2 0 3级 4级
无胃肠道穿孔,瘘以及动脉栓塞发生 无≥2级的出血事件发生
最常见的1/2级不良事件 为疼痛， 体质改变，肝损， 贫血，蛋白尿和生殖泌尿 系统疾病
GOG 170D: Avastin单药治疗卵巢癌复发的 II 期临床试验– 特性
Characteristic
FIGO stage (%) IIB IIIA IIIB 2 2 8
(n=62)
IIIC
IV Primary site (%)
77
11
EOC PPC No. of prior regimens (%) 1
Avastin+CP
Avastin维持一线治疗卵巢癌的 II 期临床试验 – 试验设计
新诊断的 ≥IC期卵巢癌* (n=62)
Carboplatin (AUC 5)/ paclitaxel 175mg/m2 q3w x6–8 + Avastin 15mg/kg q3w‡
Avastin 15mg/kg q3w for 12 months
•
初治卵巢癌的 II 期临床试验
Micha et al. Int J Gynecol Cancer 2007 Penson et al, J Clin Oncol 2010
•
初治卵巢癌的 III 期临床试验
GOG-0218, ASCO 2010 ICON7/OVAR11, IGCS & ESMO 2010
Avastin in ovarian cancer: clinical trials
Avastin在卵巢癌的相关研究
•
复发卵巢癌的 II 期临床试验
Burger RA, et al. J Clin Oncol 2007 Cannistra SA, et al. J Clin Oncol 2007 Garcia AA, et al. J Clin Oncol 2008
•
进行中/完成的临床试验
OCEANS (铂类敏感) AURELIA (铂类耐药) GOG-0213 (铂类敏感)
GOG 170D: Avastin单药治疗卵巢癌复发的 II 期临床试验 – 试验设计
既往治疗后进展卵巢癌* (n=62)
Avastin 15mg/kg every 3 weeks
Penson, et al. JCO 2010
Avastin+CP
Avastin维持一线治疗卵巢癌的 II 期临床试验 – 疗效总结
Efficacy compares favourably to data for carboplatin/paclitaxel in this setting
Efficacy data ORR (RECIST), % (95% CI) Complete response Partial response Stable disease (RECIST), % (95% CI) Median PFS, months (95% CI) Median OS (months)
NR = not reached
(n=62) 75 (62–85) 23 (13–36) 52 (38–65) 25 (15–37) 29.8 (17.3–NR) NR
Data for the primary efficacy endpoints are shown in bold Penson, et al. JCO 2010
Avastin+CP
Avastin维持一线治疗卵巢癌的 II 期临床试验 –化疗的安全性
16
14
12 Patients (%) 10 8
3级 4级
6
4 2 0
3/4级不良事件的种类和发生率与已知的Avastin和CP的相关耐受分析相一致
*All allergic reactions were to paclitaxel Penson, et al. JCO 2010
n Single-agent Avastin Burger 20071 Cannistra 20072 Smerdel 20093 Garcia 20084 McGonigle 20085 Kikuchi 20096 Muggia 20097 Nimeiri 20088 Platinum-sensitive9–11 Platinum-resista22 21 13
84 16
34 66 68 32 58
GOG 170D: Avastin单药治疗卵巢癌复发的 II 期临床试验– 疗效总结
疗效似乎更支持其他的单药治疗方案
Efficacy data ORR*, % (90% CI) Complete response, %(n) Stable disease*‡, %(n) 6-month PFS, % (90% CI) Median PFS (months) Median OS (months)
PD

主要研究终点: 6-month PFS 和 ORR 次要研究终点:安全性, OS, PFS


第三研究终点:可能影响 PFS的因素
*1–2 prior cytotoxic regimens (first platinum-based, with a second platinum-based regimen if platinum-free interval ≥12 months) Burger, et al. JCO 2007