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Combining bevacizumab with standard chemotherapy reduced the risk of disease progression by 52% in patients with platinum-resistant ovarian cancer.
Eric Pujade-Lauraine, MD, PhD
Combining bevacizumab (Avastin, Genentech) with standard chemotherapy reduced the risk of disease progression by 52% in patients with platinum-resistant ovarian cancer, according to a phase III study presented at the 2012 American Society of Clinical Oncology (ASCO) annual meeting.
Lead investigator Eric Pujade-Lauraine, MD, PhD, and colleagues wrote that this is the first phase III trial to demonstrate a benefit with a targeted therapy in this patient population.
“This is a breakthrough that will change the practice of treating patients with ovarian cancer,” said Pujade-Lauraine, a professor at the UniversitÃ© de Paris Descartes, France, and head of the Group d’Investigateurs Nationaux pour l'Etude des Cancers Ovariens, a clinical trials cooperative group based in France.
In the phase III AURELIA study, Pujade-Lauraine et al accrued 361 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer previously treated with at least four cycles of platinum-based chemotherapy whose disease had progressed within six months of their last platinum therapy treatment.
Based on their previous treatment experience, patients were first assigned standard chemotherapy with weekly paclitaxel, topotecan, or liposomal pegylated doxorubicin. Patients were then randomized 1:1 to receive chemotherapy alone (n = 182) or combination therapy with bevacizumab (n = 179).
The results showed that patients receiving bevacizumab had a statistically significant 3.3-month progression-free survival (PFS) benefit as compared with the chemotherapy-only group (6.7 months vs 3.4 months; hazard ratio, 0.48; P <.001). Additionally, the objective response rate was 30.9% with the bevacizumab combination versus 12.6% with chemotherapy alone.
Patients in the chemotherapy-only arm whose disease progressed were allowed to cross over to bevacizumab monotherapy.
Toxicity levels with bevacizumab added to chemotherapy were manageable, according to Pujade-Lauraine. Adverse events greater than grade 2, including hypertension, proteinuria, gastrointestinal perforations, and fistula or abscesses, were higher in the bevacizumab group; however, grade 3 adverse events were commensurate between the treatment arms.
Pujade-Lauraine said bevacizumab tolerance was bolstered by patient selection criteria that excluded individuals with digestive symptoms such as a history of bowel obstruction/abdominal fistula or clinical/radiological evidence of rectosigmoid involvement.
The AURELIA study is now the fourth phase III trial in which bevacizumab has extended PFS in patients with ovarian cancer. Previously, the GOG-0218 (N Engl J Med. 2011;365:2473-2483) and ICON7 (N Engl J Med. 2011;365:2484-2496) studies showed a PFS benefit for bevacizumab in the frontline treatment of advanced ovarian cancer. The OCEANS trial (J Clin Oncol. 2012. doi: 10.1200/JCO.2012.42.0505) demonstrated that bevacizumab also delayed disease progression in patients with recurrent, platinum-sensitive disease.
Based on the results of the GOG-0218 and ICON7 studies, the European Commission approved bevacizumab in women with newly diagnosed, late-stage ovarian cancer.
In the United States, bevacizumab is FDA-approved to treat colorectal, brain, lung, and kidney cancer, but it does not yet have an approved indication in ovarian cancer.
Manufacturers Genentech and Roche are being careful with their FDA filing for an ovarian cancer indication for bevacizumab, given their recent experience with the drug’s breast cancer indication.
In late 2011, bevacizumab’s breast cancer indication was revoked by the FDA, even though clinical trial results had demonstrated that the drug prolonged disease-free progression. The drug’s lack of an overall survival (OS) benefit was a major factor in the FDA’s decision.
Similarly, none of the four phase III trials demonstrating bevacizumab’s PFS benefit in ovarian cancer has thus far produced mature data showing a significant OS benefit. However, in a press briefing at ASCO, moderator Carol Aghajanian, MD, chief, Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York City, indicated that she does not consider this lack of OS data to be a definitive hindrance to FDA approval.
Aghajanian said that since bevacizumab is an angiogenesis inhibitor that targets the vascular endothelial growth factor (VEGF) pathway and VEGF is particularly important to the growth of ovarian cancer, it helps the drug’s approval chances. She added that the consistent data across the various phase III studies also differentiates bevacizumab’s ovarian cancer outlook from the data that influenced the FDA’s breast cancer decision.
“In breast cancer it was a different issue where accelerated approval was given and then follow-up studies were done that did not all show the same result or the same magnitude of result. So there were differences in results across trials which we haven’t seen here in ovarian cancer,” Aghajanian said.
Pujade-Lauraine added that when specifically considering an indication for platinum-resistant ovarian cancer, the likelihood of FDA approval is also bolstered by the high unmet medical need of patients in this subset.
Pujade-Lauraine E, Hilpert F, Weber B, et al. AURELIA: A randomized phase III trial evaluating bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. J Clin Oncol. 2012;30(suppl; abstr LBA5002).