Results of an early analysis of a phase II clinical trial presented at the 2012 San Antonio Breast Cancer Symposium show that combining the aromatase inhibitor letrozole (Femara) with the study medicine PD-0332991 (PD-991) increased median progression-free survival (PFS) by 18.6 months compared to taking letrozole alone. Progression-free survival is the length of time during and after treatment that the disease does not grow or spread.
PD-991 was tested in women with estrogen receptor-positive, HER2 negative metastatic breast cancer. The trial is ongoing but has stopped recruiting new participants. A larger phase III trial is planned for 2013.
PD-991 is a kinase inhibitor, a medicine that targets a specific kind of enzyme that plays a part in cell division and growth, called kinase. PD-991 works against cyclin-dependent kinase (CDK) 4 and 6, two that are known to aid tumor cell growth.
Letrozole, an aromatase inhibitor, is a common treatment for estrogen receptor-positive breast cancer. Aromatase inhibitors block the enzyme aromatase to stop the body from making the estrogen that fuels tumor growth in ER positive cancer.
Positive results in preclinical studies led researchers to explore whether combining PD-991 with letrozole would better treat ER positive metastatic breast cancer. This is one of the first studies to test PD-991 in people.
Sixty-six postmenopausal women with ER positive, HER2 negative metastatic breast cancer were randomly assigned to one of two treatment arms:
- Women in arm I received letrozole plus PD-991, both by mouth
- Women in arm II took letrozole alone, by mouth
Women received treatment until side effects became too dangerous, the cancer progressed, or they withdrew from the trial.
This trial was open-label, meaning the women and study doctors knew which treatment was given. Tumor progression was assessed every two months.
This study has two parts; the data presented at San Antonio represent the first part. Women in the combination arm took treatment an average of 47 weeks; those in the letrozole arm, an average of 24 weeks. Overall, this study found:
- Progression-free survival with letrozole plus PD-991 was 26.1 months, compared to 7.5 months with letrozole alone.
- Participants on combination therapy saw a 45 percent response rate, versus 31 percent for those who took letrozole alone. Response rate represents the percentage of participants whose cancer shrinks during or after treatment.
- The clinical benefit rate improved by 26 percent with combination therapy, from 44 percent with letrozole alone to 70 percent with combination therapy. Clinical benefit rate is determined by adding the number of participants with complete response, or tumor disappearance, and partial response, tumor shrinkage, with the number of participants whose disease did not progress for more than 24 weeks.
- The most common side effects were low blood counts and fatigue.
What This Means For You
Though it will not immediately change the standard available treatments for the disease, the positive results of this phase II trial support the need for further research of both combination and targeted therapies for ER positive, HER2 negative metastatic breast cancer.
If you have ER positive metastatic disease and are interested in PD-991 as a treatment option, talk with your doctor about your eligibility for the phase III clinical trial set to recruit participants beginning in 2013.
Note: LBBC will link to the abstract when it becomes publicly available.