The PALOMA-3 trial examining an Ibrance (palbociclib) regimen in HR-positive/HER2-negative breast cancer was halted after an independent panel determined it met the primary endpoint of improving progression-free survival.
The PALOMA-3 trial examining an Ibrance (palbociclib) regimen in HR-positive/HER2-negative breast cancer was halted after an independent panel determined it met the primary endpoint of improving progression-free survival (PFS). The results were announced by Pfizer, the company developing Ibrance, which noted that these are the first randomized phase 3 data reported for the CDK 4/6 inhibitor.
“We’re gratified to be able to stop the trial early and are engaging in discussions with health authorities regarding a regulatory path forward,” Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology, said in a statement.
The multicenter PALOMA-3 study randomized 521 patients with metastatic breast cancer whose disease progressed on or following endocrine treatment in a 2:1 ratio to fulvestrant plus either placebo or Ibrance. Faslodex was administered at 500 mg (IM) on days 1 and 15 of cycle 1, and then on day 1 of each cycle thereafter, and patients received oral Ibrance at 125 mg/day continuously for the first 3 weeks of each cycle, followed by 1 week off. Treatment cycles were 28 days for both arms.
Beyond the primary PFS endpoint, secondary endpoints for the trial included overall survival, objective response, and duration of response. The adverse events reported for the Ibrance/fulvestrant combination were commensurate with those observed with previous single-agent use of the drugs. Pfizer intends to submit the full results from the study for presentation at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in June.
While not approved for the use explored in PALOMA-3, Ibrance has received an accelerated approval as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer, based on findings from the phase 2 PALOMA-1 trial.
In the open-label phase 2 study, treatment with Ibrance plus letrozole reduced the risk of disease progression by 51 percent compared with letrozole alone. The median PFS with Ibrance was 20.2 versus 10.2 months for letrozole alone.
PALOMA-1 trial randomized 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer in a 1:1 ratio in two parts: Part 1 contained 66 patients and Part 2 had 99 patients. Continuous daily letrozole was administered at 2.5 mg with or without Ibrance at 125 mg daily for 3 weeks followed by 1 week of rest until progression. The primary endpoint was PFS by investigator assessment.
The rate of grade 3/4 neutropenia was significantly higher in the Ibrance arm compared with letrozole alone (54 percent versus 1 percent). Additionally, the rate of grade 3/4 leucopenia (19 percent versus 0 percent) and fatigue (4 percent versus 1 percent) were higher with Ibrance. No cases of febrile neutropenia or neutropenia-related infections were reported in the study.
Altogether, 13 percent of patients discontinued treatment as a result of side effects in the Ibrance arm compared with 2 percent for letrozole. The most frequently reported serious adverse events with the combination were pulmonary embolism (4 percent) and diarrhea (2 percent).
At the time of approval, PALOMA-1 coauthor Dennis Slamon heralded the decision. “With the FDA approval, this study represents a potential practice-changing result. I believe palbociclib will now become a standard treatment approach for postmenopausal women with ER+/HER2- metastatic breast cancer,” Slamon, a professor of medicine and director of the Revlon/UCLA Women’s Cancer Research Program, said in a statement.
The confirmatory phase 3 trial for Ibrance's accelerated approval is PALOMA-2. This study is comparing the combination of Ibrance and letrozole with letrozole alone as a frontline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer (NCT01740427).
As Pfizer awaits the PALOMA-2 data, Rothenberg noted that the company is pleased with what the PALOMA-3 outcomes have shown. “The results of this trial are especially important because they help us understand the potential of Ibrance to improve outcomes in patients with this difficult to treat cancer.”