Primary endpoint was achieved, but secondary marker of OS is yet to be analyzed.
Roche reports that its Her2-targeted medicine pertuzumab met the primary endpoint of extending progression-free survival (PFS) and did not achieve one of two secondary endpoints, boosting overall response rate. The other secondary endpoint was the measure of overall survival, which was not statistically significant at this time, but a final analysis is expected to take place in 2013.
Roche has submitted a BLA and MAA for people with previously untreated, Her2-positive metastatic breast cancer. The results announced today are from the Cleopatra study, which enrolled 808 people with previously untreated Her2-positive metastatic breast cancer. The trial was set up as a randomized, double-blind, placebo-controlled study to evaluate pertuzumab combined with Herceptin and chemotherapy compared to Herceptin and chemotherapy alone.
People who received pertuzumab experienced a 38% reduction in the risk of their disease worsening or death, Roche says. Median PFS improved by 6.1 months from 12.4 months for Herceptin and chemotherapy alone.
Interim OS analysis took place when 43% of events that were planned for final overall survival analysis had occurred. At the time of this evaluation, patients in both treatment arms had been followed for OS for a median of 19.3 months. The data showed a trend suggestive of a survival benefit in favor of combining pertuzumab and Herceptin with chemo. The hazard ratio did not meet the stopping boundary, however, and pivotal data is expected in two years or so.
ORR was 80.2% and 69.3% in the pertuzumab arm and control arm, respectively. Since interim OS did not reach statistical significance, the statistical test result for ORR has been deemed exploratory.
Rates of grade ≥3 adverse events with more than a 2% difference between arms were observed for neutropenia, febrile neutropenia, and diarrhea with 48.9%, 13.8%, and 7.9%, respectively, in the pertuzumab arm compared with 45.8%, 7.6%, and 5.0% respectively, in the control arm.
The mechanisms of action of pertuzumab and Herceptin are believed to complement each other. Both bind to the Her2 receptor but on different regions, according to Roche. The mAb therapeutic is designed specifically to prevent the Her2 receptor from pairing with other Her receptors (EGFR/Her1, Her3, and Her4).
“We have been studying the Her2 pathway for 30 years to bring personalized medicines to people with Her2-positive breast cancer,” says Hal Barron, M.D., CMO and head, global product development. “These results show we may soon improve on the current standard of care, Herceptin plus chemotherapy, to further help people with this advanced form of the disease.”
Pertuzumab is also being studied in early Her2-positive breast cancer and advanced Her2-positive gastric cancer.