Neratinib combined with standard chemotherapy was found to be a beneficial treatment for some women with newly diagnosed, high-risk breast cancer.
Additionally, researchers learned that an algorithm used in the adaptive, randomized trial known as I-SPY 2 was highly effective at predicting the success of the treatment regimen in the patients who have HER2-positive/HR-negative disease. The finding marks the second drug graduation within the I-SPY 2 trial model.
Data from the phase II trial were presented at the annual meeting of the American Association for Cancer Research.
Launched by UC San Francisco in tandem with a private-public partnership, I-SPY 2 combines personalized medicine with a novel investigational design. Its goals are to improve the efficiency of clinical trials and to streamline the process for developing new drugs and regimens.
“What is so exciting about the graduations is that we’re proving unconditionally that the standing trial mechanism can efficiently evaluate multiple drugs and identify the specific populations for which the agents are most effective,” said Laura Esserman, professor of surgery and director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center.
Esserman is the co-principal investigator of I-SPY 2, which is underway at 20 cancer research centers in the U.S. and Canada.
“We are testing the agents in high-risk patients at a time in their disease (primary breast cancer) when we are most likely to make a difference in survival,” Esserman said. Under the I-SPY 2 model, the costs, time and number of patients required to safely test a drug would be reduced by more than a third, according to researchers.
Surgery to remove tumors is not undertaken until after the drug treatment is completed. As a result, the response of the tumor to new therapies becomes critical evidence in gauging whether a drug is effective.
Another feature of the trial is that it screens multiple drugs from multiple companies, allowing the researchers to graduate, drop and add drugs seamlessly throughout the course of the trial without requiring FDA approval for a new protocol. To date, seven agents have been incorporated, two have graduated and more are being prepared to enter the trial.
According to the findings presented, the algorithm randomly assigned 115 patients to the branch of the trial that contained neratinib. The results were compared with those of 78 patients who were concurrently randomized to a control arm containing standard chemotherapy.
The trial’s adaptive randomization successfully identified HER2+/HR- as the drug’s biomarker signature. It also identified two other signatures, all HER2 and MP+ tumors that might also benefit from the regimen. Neratinib is in development at Puma Biotechnology Inc. for the treatment of early and late-stage breast cancer and under consideration for the I-SPY 3 phase III trial.
The I-SPY 2 partnership includes the FDA, the Foundation of the National Institutes of Health, QuantumLeap Healthcare Collaborative, pharmaceutical companies and academic medical centers.
Palbocicilib Doubles PFS in Phase II Trial to 20.2 Months
Progression-free survival was effectively doubled in women with advanced breast cancer who took palbocicilib in a phase II trial.
The study was performed in 165 post-menopausal breast cancer patients with advanced ER+, HER2- disease. Results of the trial were announced at the annual meeting of the American Association for Cancer Research.
Progression-free survival was 20.2 months for patients who received palbociclib plus letrozole and 10.2 months for those who received letrozole alone. The PFS results indicated a 51 percent reduction in the risk of disease progression with the addition of palbociclib to letrozole.
Palbociclib (PD 0332991) was given breakthrough therapy designation by the FDA earlier this year. It is sponsored by Pfizer Inc.
