The anticipated approval of Ibrance (palbociclib) came two months ahead of expectations, as the FDA granted an accelerated approval to the drug as a frontline treatment for women with ER-positive, HER2-negative metastatic breast cancer.
The anticipated approval of Ibrance (palbociclib) came two months ahead of expectations, as the Food and Drug Administration (FDA) granted an accelerated approval to the drug as a frontline treatment for women with ER-positive, HER2-negative metastatic breast cancer. Ibrance was approved under the FDA's breakthrough therapy designation and priority review program, which provides an expedited approval process for treatments that provide a substantial benefit over current options. The FDA was not scheduled to make a decision on the drug's application until April 2015.
In the phase 2 PALOMA-1 study, treatment with the novel CDK 4/6-inhibitor Ibrance plus Femara (letrozole) reduced the risk of disease progression by 51 percent compared with Femara alone. The median progression-free survival (PFS) with Femara was 20.2 versus 10.2 months for Femara alone.
"With the FDA approval, this study represents a potential practice-changing result," the study’s coauthor Dennis Slamon, professor of medicine and director of the Revlon/UCLA Women’s Cancer Research Program, said in a statement. "I believe palbociclib will now become a standard treatment approach for postmenopausal women with ER+/HER2- metastatic breast cancer."
Gloria Zollar, initially diagnosed with breast cancer in 2002, had a recurrence in 2010 when the cancer spread to her bones. Her oncologist told her about a phase 2 trial testing a new type of breast cancer drug. She says she had no hestitation joining the study.
"When Dr. Patel asked me about it and said it would seem to help, I said fine. I trusted him very much," she says. A year later, her tumors had stopped progressing. Today, she is in remission and continues taking Ibrance and daily Femara.
The PALOMA-1 trial randomized 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer in two parts: Part 1 contained 66 patients and Part 2 had 99 patients. Continuous daily Femara was administered at 2.5 mg with or without Ibrance at 125 mg daily for three weeks followed by one week of rest until progression. At the final analysis from the trial that was presented in April 2014, the median overall survival (OS) was 37.5 months with Ibrance compared with 33.3 months with Femara alone. However, this first analysis of OS contained data from only 61 patients (37 percent) and was not deemed statistically significant.
In Part 1 of the study, the median PFS was 26.7 months with Ibrance versus 5.7 months for Femara alone. In the larger Part 2, the median PFS was 18.1 versus 11.1 months, for Ibrance combination and Femara, respectively. The combination resulted in a response rate of 45 percent compared with 31 percent for the monotherapy and the overall clinical benefit rate was 70 percent versus 44 percent.
"Palbociclib is the first drug in its class to be approved by the FDA," lead investigator Richard Finn, from the Jonsson Comprehensive Cancer Center at UCLA, said in a statement. "What is really remarkable is that we doubled the median progression-free survival. That type of result is not often seen in cancer medicine."
The rate of moderate neutropenia was significantly higher in the Ibrance arm compared with Femara alone (54 percent versus 1 percent). Additionally, the rate of moderate leucopenia (19 percent versus 0) and fatigue (4 percent versus 1 percent) were higher with Ibrance. Altogether, 13 percent of patients discontinued treatment as a result of side effects in the Ibrance arm compared with 2 percent for Femara.
A number of phase 3 clinical trials are exploring Ibrance as a treatment for patients with advanced breast cancer. Given the benefit demonstrated in the PALOMA-1 trial, many of these studies will be randomized in a 2:1 ratio favoring treatment with the new drug.
The PALOMA-2 trial is comparing the combination of Ibrance and Femara compared with Femara alone as a frontline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer (NCT01740427). The PALOMA-3 trial is comparing Ibrance plus Faslodex (fulvestrant) against Faslodex alone in women with ER-positive, HER2-negative metastatic breast cancer following progression on prior endocrine therapy (NCT01942135).
Additionally, the open-label phase 3 PEARL trial will compare Aromasin (exemestane) plus Ibrance with Xeloda (capecitabine) for patients with ER-positive metastatic breast cancer who are resistant to treatment with non-steroidal aromatase inhibitors (NCT02028507). The phase 3 PENELOPE-B trial will examine post-neoadjuvant treatment with Ibrance plus endocrine therapy in ER-positive patients with residual disease following chemotherapy and surgery (NCT01864746). Both of these studies are currently enrolling patients.