Combining Chemotherapy with Bevacizumab
Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients
Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival. Longer follow-up is needed to confirm the trends, but, if upheld, the results of these trials would support the first use of a biologic agent to treat ovarian cancer. Data from both trials were presented last week at the ASCO annual meeting in Chicago.
In the OCEANS study, 484 women whose cancers recurred more than 6 months after a single prior regimen of chemotherapy were randomly assigned to receive chemotherapy with carboplatin and gemcitabine plus bevacizumab or a placebo. After six cycles of chemotherapy, the patients continued to receive bevacizumab or the placebo until evidence of tumor progression was seen. Those who received bevacizumab had a 52 percent increase in the time it took their disease to progress compared with those who received placebo (12.4 months versus 8.4 months, respectively).
Tumor shrinkage was observed in 79 percent of the patients treated with bevacizumab, compared with only 57 percent of those receiving the placebo. The duration of tumor response was also longer in patients receiving bevacizumab by an average of 3 months. Side effects were similar to those seen in other studies of bevacizumab, such as increased hypertension and proteinuria. No gastrointestinal perforations were reported.
“This regimen should be considered a new option for women with recurrent ovarian cancer [whose cancer responded to plantinum-based chemotherapy],” said the study’s lead investigator Dr. Carol Aghajanian of Memorial Sloan-Kettering Cancer Center.
In the second trial, known as ICON7, 1,528 women with newly diagnosed high-risk or advanced ovarian cancer were randomly assigned to six cycles of chemotherapy with carboplatin and paclitaxel alone or to six cycles of chemotherapy with bevacizumab, followed by bevacizumab alone for 12 cycles. The addition of bevacizumab modestly increased the time it took patients’ tumors to grow, from 17.4 months to 19.8 months. An interim analysis of overall survival showed fewer deaths among patients who received bevacizumab, but this difference was not statistically significant.
The subgroup of patients at the highest risk of recurrence—patients with stage IV disease or those with stage III disease who had more than 1 cm in diameter of remaining tumor after debulking surgery—had a statistically significant improvement in overall survival, 36.6 months versus 28.8 months, and a 36 percent reduction in the risk of death.
Longer follow-up is needed to more definitively determine whether there is an overall survival benefit for high-risk patients, acknowledged the study’s lead investigator, Dr. Gunnar Kristensen of the Norwegian Radium Hospital in Oslo. But, he continued, the current data suggest that, for these patients, bevacizumab “may be of clinical relevance.”
The results from the OCEANS and ICON7 trials—and results from a trial reported at last year’s ASCO meeting, GOG 218, which showed a nearly 4-month improvement in progression-free survival for women who received chemotherapy and bevacizumab as initial therapy for advanced ovarian cancer—are not yet enough to support using bevacizumab to treat ovarian cancer, said Dr. Ursula Matulonis of the Dana-Farber Cancer Institute.
The findings to date, she continued, “are certainly very exciting.” But given the potential serious side effects of bevacizumab, particularly bowel perforation, it’s important to proceed with caution. “Ideally, we would have a biomarker that would predict responsiveness to bevacizumab,” Dr. Matulonis said, “one that identifies an angiogeneic subtype that you could use to select patients who would benefit most.”