by Marybeth Burke – Adding bevacizumab to chemotherapy halves the risk of the disease getting worse in platinum resistant patients with ovarian cancer, according to a study released at the American Society of Clinical Oncology (ASCO) conference in Chicago in June.
“These results are very significant because the addition of bevacizumab offers a new treatment option for the 20 percent of women who have primary platinum-resistant disease, as well as those whose disease later becomes platinum-resistant,” said lead study author Eric Pujade-Lauraine, MD, PhD, professor Universite de Paris Descartes, France.
This is “the first trial to show some improvement in this group of patients. It represents an unmet clinical need,” said Carol Aghajanian, MD, Chief of the Gynecologic Medical Oncology Service and a member of ASCO’s Cancer Communications Committee.
“I think it will change practice, but of course we need to wait for approval of the drug in this setting,” Dr Pujade-Lauraine said.
Three Phase III trials in ovarian cancer (OC) (two front line, one platinum (PT)-sensitive recurrent) have shown that when bevacizumab is given in addition to chemotherapy, bevacizumab significantly improved progression-free survival (PFS) vs chemotherapy (CT) alone. Aurelia is the first randomized trial of bevacizumab in PT-resistant OC.
Eligible patients had OC that had progressed £6 months after ³4 cycles of PT-based therapy. Patients with refractory OC, history of bowel obstruction, or >2 prior anticancer regimens were ineligible. After CT selection by the investigator (pegylated liposomal doxorubicin [PLD], topotecan [TOP], or weekly paclitaxel [PAC]), patients were randomized to CT either alone or with bevacizumab (10mg/kg q2w or 15mg/kg q3w depending on CT) until progression (PD), unacceptable toxicity, or withdrawal of consent, according to Abstract 5002.
Patients in the CT-alone arm could cross over to bevacizumab monotherapy at PD. The primary endpoint was PFS by RECIST. Secondary endpoints included objective response rate (ORR), overall survival, safety, and quality of life. The study design provided 80% power to detect a PFS hazard ratio (HR) of 0.7 with 2-sided log-rank test and a=0.05 after 247 events, assuming median PFS of 4.0 months with CT and 5.7 months with CT=bevacizumab.
Between October 2009 and April 2011, 261 patients were randomized to receive selected CT (PLD:126; PAC: 115; TOP:120) alone or with bevacizumab. Median follow-up after 301 PFS events was 13.5 months.
“Adverse events were higher in the bevacizumab group including greater than grade 2 hypertension (20% vs. 7%), proteinuria (11% vs. 1%), gastrointestinal perforations (2 percent v. 0), and fistula or abscesses (2% vs. 0),” according to ASCO press communications.
“In PT-resistant OC, bevacizumab plus chemotherapy provides statistically significant and clinically meaningful improvement in PFS and ORR vs CT alone. Strict inclusion criteria minimized the incidence of bevacizumab adverse events,” according to the abstract.