Pfizer (PFE) Announces Publication of Positive Phase 3 PALOMA-2 Data; Strong PFS Results Noted

November 16, 2016 5:10 PM EST

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Pfizer Inc. (NYSE: PFE) announced that detailed results from the Phase 3 PALOMA-2 trial were published in The New England Journal of Medicine. These data, presented at the 52nd American Society of Clinical Oncology (ASCO) Annual Meeting in June, further demonstrate the clinical benefit of IBRANCE® (palbociclib) as initial therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer. The PALOMA-2 study showed the combination of IBRANCE and letrozole extended progression-free survival (PFS), or the amount of time before tumor growth, by more than 10 months compared with letrozole plus placebo. Further, the study demonstrated that the median PFS of the IBRANCE and letrozole combination exceeded two years – making it the first and only treatment for this population of women to do so in a randomized Phase 3 study.1

“The median PFS of more than two years observed in this study is unprecedented for this patient population,” said Veronique Dieras, M.D., medical oncologist and head of clinical research, Clinical Investigational Unit Chef de Service Recherche Clinique, Unité d'Investigation Clinique Department of Medical Oncology, Institut Curie, Paris, France. “Building on the Phase 2 PALOMA-1 data, the results of PALOMA-2 provide additional evidence that the combination of IBRANCE and letrozole is a meaningful advancement for these women.”

“Since its accelerated approval in 2015, IBRANCE in combination with letrozole has become a standard of care for the treatment of post-menopausal women with ER+, HER2- advanced or metastatic breast cancer,” said Hope Rugo, M.D., 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. “We now have seen consistent results across three randomized trials in which the addition of IBRANCE to an endocrine therapy significantly prolonged PFS compared to the endocrine therapy alone.”

In the trial, median PFS for women treated with IBRANCE plus letrozole was 24.8 months (95% CI, 22.1-not estimable) 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<0.001), a 42% reduction in the risk of disease progression.

“IBRANCE has raised the bar for new treatments in hormone-receptor positive advanced breast cancer. The results of this Phase 3 trial add to the growing body of clinical data in support of IBRANCE and translates into hope for patients,” said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. “We look forward to sharing the full PALOMA-2 data with global regulatory authorities with the goal of making IBRANCE available to more women around the world. Pfizer is proud of being a leader in the development of innovative therapies like IBRANCE that make a meaningful difference in patients' lives.”

Safety results were consistent with PALOMA-1 and no major unexpected safety findings were observed. The most common grade 3/4 adverse events with IBRANCE plus letrozole versus placebo plus letrozole were neutropenia (66.4% vs 1.4%), leukopenia (24.8% vs 0%), infections (6.5% vs 3.2%) and anemia (5.4% vs 1.8%). Febrile neutropenia was reported in 1.8% of patients in the IBRANCE plus letrozole group and none of the patients in the placebo plus letrozole group. For more information, please see Important Safety Information for IBRANCE below.2

IBRANCE first was approved by the U.S. Food and Drug Administration (FDA) in February 2015 and is indicated for the treatment of hormone receptor positive (HR+), HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.2 The indication in combination with letrozole was approved under accelerated approval based on PFS results from the Phase 2 PALOMA-1 study. As stated at the time of the approval, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the double-blind, Phase 3 PALOMA-2 study.2 A supplemental New Drug Application to support the conversion of the accelerated approval to regular approval based on the results of PALOMA-2 has been submitted to the FDA.

IBRANCE also is approved in the U.S. for the treatment of HR+, HER2-advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy based on results from the Phase 3 PALOMA-3 study.2

Since the initial approval in February 2015, more than 40,000 women have been prescribed IBRANCE by more than 8,500 prescribers in the U.S.

As previously disclosed, the European Commission has approved IBRANCE for the treatment of women with HR+, HER2- locally advanced or metastatic breast cancer. The approval is for IBRANCE to be used in combination with an aromatase inhibitor. The approval also covers the use of IBRANCE in combination with fulvestrant in women who have received prior endocrine therapy. In total, IBRANCE is approved in more than 50 countries.

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.

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

About IBRANCE® (palbociclib) 125 mg capsules

IBRANCE is the first and only FDA approved oral inhibitor of CDKs 4 and 6,2 which are key regulators of the cell cycle that trigger cellular progression.3,4 In the U.S., IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.2 The indication in combination with letrozole is approved under accelerated approval based on PFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, PALOMA-2.2

Important IBRANCE (palbociclib) Safety Information from the U.S. Prescribing Information

Neutropenia was the most frequently reported adverse reaction in PALOMA-1 (75%) and PALOMA-3 (83%). In PALOMA-1, Grade 3 (57%) or 4 (5%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (56%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in about 1% of patients exposed to IBRANCE. 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 14 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.

Pulmonary embolism (PE) has been reported at a higher rate in patients treated with IBRANCE plus letrozole in PALOMA-1 (5%) and in patients treated with IBRANCE plus fulvestrant in PALOMA-3 (1%) compared with no cases in patients treated either with letrozole alone or fulvestrant plus placebo. Monitor for signs and symptoms of PE and treat as medically appropriate.

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-1 of IBRANCE plus letrozole vs letrozole alone included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-1 reported at a higher incidence in the IBRANCE plus letrozole group vs the letrozole alone group included neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently reported serious adverse events in patients receiving IBRANCE plus letrozole were pulmonary embolism (4%) and diarrhea (2%).

Lab abnormalities occurring in PALOMA-1 (all grades, IBRANCE plus letrozole vs letrozole alone) were decreased WBC (95% vs 26%), decreased neutrophils (94% vs 17%), decreased lymphocytes (81% vs 35%), decreased hemoglobin (83% vs 40%), and decreased platelets (61% vs 16%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 of IBRANCE plus fulvestrant vs fulvestrant plus placebo included 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%), headache (26% vs 20%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-3 reported at a higher incidence in the IBRANCE plus fulvestrant group vs the fulvestrant plus placebo group included neutropenia (66% vs 1%) and leukopenia (31% vs 2%). The most frequently reported serious adverse reactions in patients receiving IBRANCE plus fulvestrant were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Lab abnormalities occurring in PALOMA-3 (all grades, IBRANCE plus fulvestrant vs fulvestrant plus placebo) were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), and decreased platelets (62% vs 10%).

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).

1 Based on a MEDLINE® literature review for Phase 3 trials in HR+/HER2- MBC treatment as of August 2016.2 IBRANCE® (palbociclib) Prescribing Information. New York. NY: Pfizer Inc: 2016.3 Weinberg RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329.4 Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22.



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