CHICAGO – 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."
Susan London/IMNG Medical Media
Dr. Carol Aghajanian
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 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.