The ASCO Post | OCTOBER 15, 2012
PAGE 26
2012 Breast Cancer Symposium Updated Results continued from page 1
BOLERO-2: 18-month Data Updated results from the pivotal phase III BOLERO-2 trial continue to show that everolimus (Afinitor) added to exemestane in metastatic breast cancer significantly delays disease progression.1 Median progression-
free survival by local assessment was 7.8 months with everolimus/exemestane vs 3.2 months with exemestane alone, for a 55% reduction in risk. By central review, median progressionB:8.625” free survivalT:7.625” was 11.0 vs 4.1 months, respectively,S:6.75” for a 62% reduction in risk. The differences in each analysis were highly significant (P < .0001).
While no significant differences in overall survival have emerged, with 200 deaths overall there were 6.8% more deaths with single-agent therapy, reported Hope Rugo, MD, of the University of California, San Francisco. An exploratory analysis of the trial suggested that adding everolimus has beneficial effects on bone turnover and breast
Cabozantinib (XL184) phase 3 trials in castration-resistant prostate cancer (CRPC) for patients with bone metastases
cancer progression in the bone.2 Bone marker levels at 6 and 12 weeks increased over baseline levels with placebo, but decreased with everolimus, for an absolute difference of 66%. At day 60, the cumulative incidence rate of progressive disease in the bone was also lower with everolimus (3.03% vs 6.16%), and this trend was sustained beyond 6��������������������� �������������������� months. The investigators suggested that everolimus is overcoming the negative effects that exemestane is known to have on bone. “In the overall population, we saw less progression in the bone in patients getting everolimus, and in the subgroup with bone metastases at baseline— which is about three-quarters of patients—we saw this as well,” Dr. Rugo said. “This is a very interesting difference that suggests there is a site-specific effect with everolimus, and we have not seen this much with other targeted agents.”
Final Analysis of RIBBON-2
CabOzantinib MET Inhibition CRPC Efficacy Trials KEY ELIGIBILITY CRITERIA •Diagnosis of CRPC •Presence of bone metastases •Prior treatment with docetaxel • Prior treatment with abiraterone and/or MDV3100 (enzalutamide) •No limit to the number of prior therapies
PRIMARY ENDPOINT
Overall Survival
Confirmed Pain Response CRPC (N=246)
CRPC (N=960) • Prior docetaxel treatment • Prior abiraterone and/or MDV3100 treatment • No limit to number of prior therapies
Cabozantinib (60 mg qd) Randomization Prednisone
Randomized, double-blind, controlled trial
• Prior docetaxel treatment • Prior abiraterone and/or MDV3100 treatment • No limit to number of prior therapies • Pain related to bone metastases
Cabozantinib (60 mg qd) Randomization Mitoxantrone + Prednisone
Randomized, double-blind, controlled trial
Visit www.COMETClinicalTrials.com/ASCOPost or call 1-855-85-COMET to learn more about these trials. © 2012 Exelixis, Inc. 210 East Grand Avenue, So. San Francisco, CA 94080 05/12
B:11.25”
PRIMARY ENDPOINT
S:9.75”
COMET-2
T:10.875”
COMET-1
The final overall survival and safety analysis of the RIBBON-2 trial revealed no improvement in overall survival (a secondary endpoint) with the addition of bevacizumab (Avastin) to secondline chemotherapy in patients with HER2-negative, bevacizumab-naive metastatic breast cancer.3 Of the 684 patients, 82% in each arm have died. Median overall survival was 17.8 months with chemotherapy alone and 18.6 months with chemotherapy plus bevacizumab, and 1-year survival rates were 69% and 71%, respectively, reported Adam M. Brufsky, MD, of the University of Pittsburgh Cancer Institute. An exploratory analysis of the triple-negative subset gave a hint of an overall survival benefit. Median survival was 17.8 months with bevacizumab vs 13.5 months with placebo, but the 15% risk reduction was not statistically significant. Updated safety results were similar to those previously reported. “As you can tell, at this point there is no statistical basis for a survival benefit with bevacizumab in RIBBON-2. We should find the phase III TANIA trial interesting. The study is evaluating second-line bevacizumab in patients pretreated with bevacizumab, with bevacizumab extended beyond progression, which may be a rational design, according to preclinical data. As of yet, however, there is no basis for using bevacizumab beyond progression,” he said.
Some Staging Evaluations Mostly Useless A systematic literature review found that staging evaluations with bone scans,