On December 6, 2017 Pfizer Inc. (NYSE:PFE) reported updated progression-free survival (PFS) results from the Phase 3 PALOMA-2 trial reinforcing the clinical benefit of IBRANCE (palbociclib) combined with letrozole (Press release, Pfizer, DEC 6, 2017, View Source [SID1234522409]). The data, which will be presented at the 2017 San Antonio Breast Cancer Symposium (SABCS) on December 8 [abstract #P5-21-03], demonstrate that the combination of IBRANCE plus letrozole reduced the risk of disease progression by 44 percent and improved median PFS by more than one year compared to letrozole plus placebo (27.6 months [95% CI: 22.4, 30.3] vs 14.5 months [95% CI: 12.3, 17.1]) when used as the initial treatment for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer (HR=0.56 [95% CI: 0.46, 0.69]). This updated, post-hoc analysis included a median follow-up of more than three years, which is the longest to date of any Phase 3 study of a CDK 4/6 inhibitor.

The updated data are consistent with results from the primary analysis for PALOMA-2, which showed a median PFS for women treated with IBRANCE plus letrozole of 24.8 months (95% CI: 22.1, NE) compared with 14.5 months (95% CI: 12.9, 17.1) for women treated with letrozole plus placebo (HR=0.58 [95% CI: 0.46,0.72], p<0.0001). Consistent with findings from the primary analysis, the updated data demonstrate that clinical benefit was observed across all patient subgroups receiving the combination of IBRANCE and letrozole. Overall survival data were not yet mature at the time of this updated PFS analysis.

"There currently is no cure for metastatic breast cancer, so prolonging progression-free survival and delaying the need for additional anticancer therapies are critical factors in treating these patients," said Hope Rugo, MD, lead author and professor of medicine and director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. "The updated findings from PALOMA-2 provide additional evidence to support the use of palbociclib with an aromatase inhibitor as a standard of care in the first-line setting for postmenopausal patients with hormone receptor-positive (HR+), HER2- metastatic breast cancer across all patient subgroups."

At SABCS, 10 additional Pfizer-sponsored abstracts will be presented evaluating IBRANCE, several of which explore further analysis of PALOMA-2 along with three real-world studies of patients treated with IBRANCE in clinical practice. These real-world data include patients who have received IBRANCE in combination with endocrine therapy in various settings and across age groups, including young women (aged 50 years and under, which functioned as a surrogate for premenopausal status in the analysis).

"The real-world data to be presented at SABCS underscore the transformational impact IBRANCE has made on the treatment of HR+, HER2- metastatic breast cancer, and provide important insights into the way in which IBRANCE is being used in clinical practice," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "The rapid adoption of IBRANCE in young women is particularly notable because premenopausal women with metastatic breast cancer historically have had fewer approved treatment options available to them than postmenopausal women. The PALOMA-3 trial of IBRANCE was the first Phase 3 trial of a CDK 4/6 inhibitor to include premenopausal women and establish its efficacy in this patient population."

The safety profile of IBRANCE in the PALOMA-2 updated analysis is consistent with previous reports and will be presented at SABCS. In the primary analysis, the most common adverse reactions (≥20%) of any grade reported in the PALOMA-2 study of IBRANCE plus letrozole vs placebo plus letrozole included neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%) and anemia (24% vs 9%).1

IBRANCE was the first CDK 4/6 inhibitor approved by any regulatory authority, and now is approved in more than 75 countries. These global approvals are based on data from the PALOMA program, including PALOMA-2 as well as the Phase 3 PALOMA-3 trial, which evaluated IBRANCE in combination with fulvestrant in pre-, peri- and postmenopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy. Pre- and peri-menopausal women enrolled in PALOMA-3 received the LHRH agonist goserelin.

To date, IBRANCE has been prescribed to more than 90,000 patients worldwide.

The full prescribing information for IBRANCE can be found at www.pfizer.com.

About PALOMA-2

PALOMA-2 is a randomized (2:1), multicenter, multinational, double-blind Phase 3 study designed to assess the PFS of IBRANCE (125 mg orally once daily for three out of four weeks in repeated cycles) in combination with letrozole (2.5 mg once daily continuously) versus letrozole plus placebo as a first-line treatment for postmenopausal women with ER+, HER2- metastatic breast cancer. PALOMA-2 evaluated a total of 666 women from 186 global sites in 17 countries.

Results from PALOMA-2 after a median 23-month follow-up were previously published in The New England Journal of Medicine in November 2016.

About IBRANCE (palbociclib) 125 mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min).