New Data Show PFS, Survival Benefits with Bevacizumab in Breast Cancer
Madrid, Spain—The positive results from 2 studies raised speculation about a possible resurrection of the breast cancer indication for bevacizumab, as reported at the 2014 European Society for Medical Oncology Congress.
In one study, adding capecitabine to bevacizumab maintenance therapy led to significant improvements in progression-free survival (PFS) and overall survival (OS) compared with bevacizumab alone in patients with HER2-negative metastatic breast cancer (mBC). The second trial demonstrated a significant improvement in PFS when bevacizumab was added to first- or second-line chemotherapy for locally advanced breast cancer or mBC.
After both presentations, breast cancer specialists seemed divided about whether the data might push bevacizumab back into the breast cancer picture in the United States.
Hope Rugo, MD, Director of Breast Oncology at the University of California, San Francisco, commented that the results of the studies did not clarify bevacizumab’s role in breast cancer. In addition, both studies showed higher rates of grade 3 toxicity with bevacizumab. The data are now unlikely to sway the FDA to revisit a breast cancer indication for bevacizumab, she said.
Edith Perez, MD, Deputy Director of the Mayo Clinic Cancer Center, Jacksonville, FL, found the results impressive, particularly those from the IMELDA trial involving capecitabine, but was unsure whether the results might resuscitate bevacizumab’s role in breast cancer in the United States.
IMELDA involved 54 international sites, where investigators enrolled patients with previously untreated HER2-negative mBC. All patients began treatment with docetaxel and bevacizumab. Patients who did not have disease progression were randomized to maintenance therapy with capecitabine and bevacizumab or to bevacizumab alone, reported Joseph Gligorov, MD, a medical oncologist at Tenon University Hospital in Paris.
The primary end point was PFS. The trial ended early after an interim analysis showed a significant advantage in favor of maintenance therapy with the combination. When the trial ended, 284 patients had been enrolled and received first-line therapy, and 185 patients entered the randomized stage of the trial.
The addition of capecitabine to bevacizumab maintenance therapy more than doubled PFS compared with bevacizumab alone (11.9 vs 4.3 months). In addition, OS was significantly prolonged with combination maintenance therapy (39 vs 23.3 months), but Dr Gligorov emphasized that survival data are immature for drawing definitive conclusions.
In the bevacizumab-alone arm, grade ≥3 adverse events (AEs) included hypertension, proteinuria, and gastroenteritis. Overall, 52% of the combination group and 30% of the bevacizumab-only group had grade ≥3 AEs.
“Adding capecitabine to maintenance bevacizumab provided statistically significant and clinically meaningful improvements in progression-free survival and overall survival at study closure, despite the smaller-than-planned sample size, because of early termination of accrual, with a manageable increase in adverse events,” Dr Gligorov concluded.
The second study, TANIA, evaluated chemotherapy with or without bevacizumab in patients with locally recurrent breast cancer or mBC that had progressed during or after first-line bevacizumab and chemotherapy. Investigators randomized 494 patients to receive the physician’s choice of chemotherapy alone or in combination with bevacizumab.
Data analysis showed a median second PFS of 4.2 months with chemotherapy alone and 6.3 months when bevacizumab was added. The difference exceeded the predefined 25% improvement in PFS with the addition of bevacizumab. However, the median second PFS fell short of expectations, because the trial had the statistical power to detect an improvement from 7 months with chemotherapy alone to 9.3 months with chemotherapy plus bevacizumab.
Grade ≥3 AEs included hypertension, proteinuria, venous thromboembolic events, febrile neutropenia, and congestive heart failure.