The U.S. Food and Drug Administration (FDA) is reviewing a request that Ibrance (palbociclib), in combination with Femara (letrozole), be used as a first-line therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer.
The request, made in what the agency calls a supplemental New Drug Application (sNDA), was also granted priority review, meaning the FDA will aim for a decision within six months instead of the usual 10 months. The action date for the Prescription Drug User Fee Act (PDUFA) is set for April 2017.
Ibrance, a first-in-class CDK 4/6 inhibitor that works to retard cell growth and division, and Femara, an aromatase inhibitor that works to reduce the amount of estrogen produced in postmenopausal women, were granted accelerated approval as a combination regimen in February 2015. If the sNDA decision is favorable, the treatment will move to regular FDA approval.
The sNDA is supported by data from the PALOMA-2 Phase 3 trial (NCT01740427), which included the same patient population as the Phase 2 PALOMA-1 trial (NCT00721409), whose findings were the basis for the FDA’s accelerated approval of the therapy.
“Since its introduction in 2015, more than 45,000 patients have been prescribed Ibrance by more than 9,000 providers in the U.S.,” Liz Barrett, global president and general manager, Pfizer Oncology, said in a press release. “We are pleased that the PALOMA-2 trial has further demonstrated the significant clinical benefit of Ibrance in the first-line setting, providing additional evidence for its continued use as a standard of care medicine.”
PALOMA-2 is a multicenter, randomized, double-blind Phase 3 trial assessing the safety and efficacy of Ibrance in combination with Femara, versus placebo and Femara, in postmenopausal women with ER+/HER2- advanced breast cancer who had not received prior systemic therapies.
The study enrolled 666 participants at 186 sites across 17 countries, and assessed progression-free survival as its primary measure. Secondary outcomes included the probability of patient survival, overall survival, objective response rate, duration of response, disease control rate, and the drug’s pharmacokinetics.
Results were presented in June during the 52nd American Society of Clinical Oncology (ASCO) Annual Meeting, and published in The New England Journal of Medicine in a manuscript titled, “Palbociclib and Letrozole in Advanced Breast Cancer.” Data revealed that patients receiving the combo treatment had improved progression-free-survival compared to the control group (24.8 months vs. 14.5 months). The safety profile of the combination treatment in Paloma-2 was consistent with the drugs’ known adverse event profiles.