Niko Andre, MD
Treatment with the combination of bevacizumab (Avastin) and chemotherapy improved progression-free survival (PFS) and overall survival (OS) in women with HER2-negative metastatic breast cancer, according to two phase III studies being presented at the 2014 ESMO Congress.
In the phase III IMELDA study, maintenance bevacizumab in combination with capecitabine improved PFS by 62% and OS by 57%. Moreover, in the phase III TANIA trial, the continuation of treatment with bevacizumab and chemotherapy beyond progression lowered the risk of progression by 25% and demonstrated an improvement in overall response rate (ORR).
"Very important data also come, again, from Avastin, also in first-line metastatic breast cancer, this time in HER2-negative patients," Niko Andre, MD, the head of global medical affairs Oncology/Hematology at Roche Pharmaceuticals, said in a video interview. "We have two trials that will be presented during this meeting. The first one will be the IMELDA trial, which looks at a sophisticated maintenance treatment schedule. The second trial, being the TANIA trial, where we now investigate the treatment beyond progression concept—that we successfully implemented in colorectal cancer already—now also in frontline metastatic breast cancer."
The open-label phase III IMELDA trial explored the safety and efficacy of maintenance bevacizumab with or without capecitabine following frontline treatment with bevacizumab plus docetaxel in patients with HER2-negative metastatic breast cancer. The primary endpoint of the study was PFS, with secondary endpoints focused on ORR and OS.
The study enrolled 284 patients, with 185 reaching randomization following 3-6 cycles of bevacizumab plus docetaxel. Bevacizumab was administered at 15 mg/kg every 3 weeks and capecitabine was administered at 1000 mg/m2
twice daily for the first two weeks of each cycle. Overall, 94 patients received bevacizumab and 91 received bevacizumab plus capecitabine.
The median OS with single-agent bevacizumab was 23.7 months versus 39.0 months with the combination (HR = 0.43; 95% CI, 0.26–0.69; P
< .001). The 1-year OS rate was 72% with single-agent bevacizumab compared with 90% for the combination. The median PFS was 4.3 months versus 11.9 months for the single-agent and combination, respectively (HR = 0.38; 95% CI, 0.27–0.55; P
The phase III TANIA trial explored continued or reintroduced bevacizumab following first-line bevacizumab plus chemotherapy in patients with HER2-negative, locally recurrent, or metastatic breast cancer. The study looked specifically at patients who responded to frontline treatment for ≥12 weeks.
In the study, 494 patients were randomized to chemotherapy (n = 247) or bevacizumab plus chemotherapy (n = 247). In general, capecitabine was the most frequently administered chemotherapeutic (approximately 60%). Crossover was not allowed following progression. The primary endpoint of the study was PFS, with OS and ORR as secondary outcome measures.
The median PFS in the single-agent chemotherapy arm was 4.2 months compared with 6.3 months with the combination (HR = 0.75; 95% CI, 0.61–0.93; P
= .0068). The ORR was 16.8% versus 20.9%, for the single-agent chemotherapy and the combination, respectively (P
= .3457). Final OS results are expected in 2015.
In addition to findings on bevacizumab in breast cancer, Roche announced a number of presentations at the ESMO meeting focused on targeted therapies. The company is presenting phase III data from the coBRIM and CLEOPATRA trials, in addition to data on the novel immunotherapy MPDL3280A.
“The data that will be presented at this year’s meeting show that cancer therapies can have even greater impact for patients when we understand which people will benefit the most from our medicines,” said Sandra Horning, Chief Medical Officer and Head, Global Product Development. “Data from many of Roche’s targeted medicines and combination approaches are being featured at ESMO this year, delivering insights about what may soon be possible for patients.”
Bevacizumab is currently approved for a number of indications, including treatment for patients with colorectal cancer, lung cancer, renal cell carcinoma, glioblastoma multiforme, and cervical cancer.
In February 2008, the combination of bevacizumab and docetaxel was granted accelerated approval by the FDA for patients with metastatic breast cancer. However, in 2011, the agency withdrew this indication due to a lack of sufficient safety and efficacy data for bevacizumab.
An application for bevacizumab in combination with chemotherapy as a treatment for patients with recurrent platinum-resistant ovarian cancer is currently pending. The expected FDA decision date for this indication is November 19, 2014.