加用贝伐珠单抗可使难治性卵巢癌无进展生存期延长1倍

芝加哥(EGMN)——美国临床肿瘤学会(ASCO)年会上公布的AURELIA研究结果显示，化疗联合抗血管生成药贝伐珠单抗的方案可为那些对铂类药物产生耐药的卵巢癌女性患者带来新的希望。

这项随机III期研究由巴黎主宫医院的Eric Pujade-Lauraine博士及其同事进行，研究对象是铂类药物末次给药后6个月内出现进展的上皮性卵巢癌、输卵管癌或原发性腹膜癌女性患者(n=361)。考虑到贝伐珠单抗的已知不良反应，研究者排除了具有肠梗阻或腹瘘病史或具有直肠乙状结肠受累征象的患者。患者随机平均分组，接受单纯化疗(3种标准药物之一：紫杉醇、拓扑替康或聚乙二醇脂质体阿霉素)或化疗+贝伐珠单抗联合治疗。单纯化疗组患者如果出现进展，可接受贝伐珠单抗单药治疗。

中位随访13.5个月后，联合治疗组和单纯化疗组的复发率分别为75%和91%。联合治疗组的中位无进展生存期(主要终点)约为单纯化疗组的2倍[6.7个月 vs. 3.4个月；危险比(HR)=0.48；P＜0.001)]。总生存结果还未可知。

在联合治疗组中观察到的不良事件与既往发表和报道的贝伐珠单抗相关不良事件一致。具体而言，联合治疗组患者更常发生≥2级高血压(20% vs. 7%)、蛋白尿(11% vs. 1%)、胃肠道穿孔(2% vs. 0%)和瘘或脓肿(2% vs. 0%)。另一方面，联合治疗组疲乏、腹痛和呼吸困难等可能与肿瘤相关的不良反应的发生率低于单纯化疗组。

Pujade-Lauraine博士认为该研究将会改变铂类药物耐药卵巢癌的临床治疗实践，但还需等待贝伐珠单抗获批用于这方面的治疗，估计下个月将会提交相关申请材料。

Pujade-Lauraine博士声明是罗氏诊断部的顾问并从该公司获得酬金和研究资金。

CHICAGO (EGMN) – The combination of an anti-angiogenic agent with chemotherapy offers new hope to women with ovarian cancer who are running out of options because their disease has become resistant to platinums, suggests a randomized phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Among the 361 women studied in the trial, known as AURELIA, median progression-free survival was 6.7 months when bevacizumab (Avastin, manufactured by Genentech/La Roche) was added to chemotherapy versus 3.4 months when chemotherapy was given alone, for a 52% relative reduction in risk.

Certain adverse events were more common with the combination but consistent with those observed previously with bevacizumab, according to data presented in a press briefing at the meeting.

“Patients with ovarian cancer in whom chemotherapy is no longer working are a high unmet medical need,” commented lead investigator Eric Pujade-Lauraine, M.D., Ph.D., an oncologist at the Hôpital Hôtel-Dieu in Paris and head of the Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO), a clinical trials cooperative group based in France. Such women make up a large share of the ovarian cancer population.

“AURELIA is a positive trial: It shows that adding bevacizumab to chemotherapy halves the risk of disease getting worse in these patients,” he maintained. “Bevacizumab plus chemotherapy should thus be considered as a new standard option in these patients with platinum-resistant disease.”

Dr. Carol Aghajanian, press briefing moderator and chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York, noted that the trial is the first to show significant improvement in platinum-resistant ovarian cancer. She drew a distinction between the breast cancer setting, in which bevacizumab has ultimately proven somewhat disappointing, and the ovarian cancer setting.

“I think there is a difference there that the VEGF [vascular endothelial growth factor] pathway is very specifically important in ovarian cancer. And in ovarian cancer, we have had three prior trials ... that were positive,” she explained, referring to the GOG-0218 and ICON7 trials in the front-line setting and the OCEANS trial in the relapsed platinum-sensitive setting. “And this one is positive as well.”

Furthermore, the regulatory pathway for approval in breast cancer differed, according to Dr. Aghajanian. “There, accelerated approval was given, and the follow-up studies were not all showing the same result or the same magnitude of result. So there were some differences in results across trials, which we haven’t seen here in ovarian cancer.”

In AURELIA, the investigators enrolled women with epithelial ovarian, fallopian tube, or primary peritoneal cancer who had progression within 6 months of their last dose of a platinum. Given the known adverse effects of bevacizumab, women were excluded if they had a history of bowel obstruction or abdominal fistula, or evidence of rectosigmoid involvement.

They were assigned evenly to receive chemotherapy (one of three standard agents: paclitaxel, topotecan, or liposomal pegylated doxorubicin) alone or with the addition of bevacizumab, which is currently approved by the U.S. Food and Drug Administration to treat colorectal cancer, glioblastoma, non–small cell lung cancer, and renal cell cancer. Patients in the former group could receive bevacizumab monotherapy if they experienced progression.

After a median follow-up of 13.5 months, the rate of recurrence was 75% in the bevacizumab-chemotherapy group, compared with 91% in the chemotherapy group, Dr. Pujade-Lauraine reported.

Median progression-free survival, the trial’s primary endpoint, was almost doubled with the combination (6.7 vs. 3.4 months; hazard ratio, 0.48; P less than .001).

“ ‘Wow!’ – that’s exactly what the investigators said when they saw this graph,” he related. “The separation between the two curves clearly indicates that adding bevacizumab to chemotherapy is working very well.” Overall survival results are not yet mature.

Adverse events “were very consistent with those already published and reported with bevacizumab,” Dr. Pujade-Lauraine noted. Specifically, patients in the bevacizumab-chemotherapy group were more likely to experience grade 2 or higher hypertension (20% vs. 7%), proteinuria (11% vs. 1%), gastrointestinal perforation (2% vs. 0%), and fistula or abscess (2% vs. 0%).

On the flip side, “we saw some side effects which could be related to tumor were decreased in the bevacizumab-plus-chemo arm compared to the chemo arm, such as fatigue, abdominal pain, dyspnea,” he pointed out.

“I think [the AURELIA trial] will change practice,” Dr. Pujade-Lauraine concluded. “But of course, we need to wait for the approval of the drug in this setting. And I think that is something which will be filed in the next month.”

Dr. Pujade-Lauraine disclosed that he is a consultant to and receives honoraria and research funding from Roche Diagnostics. The trial was sponsored by Hoffman-La Roche. Dr. Aghajanian disclosed no relevant conflicts of interest.