Pfizer Announces Real-World Evidence Demonstrating Superior Efficacy of First-Line Ibrance (palbociclib) Plus Letrozole in HR+/HER2− Metastatic Breast Cancer

March 28, 2021/BioonBIOON/--Pfizer(Pfizer) recently announced that real-world evidence (RWE), published in a peer-reviewed journal, demonstrates: in HR+/HER2- metastaticBreast CancerIn female patients with metastatic breast cancer (mBC), first-line treatment with the targeted anticancer drug Ibrance® (generic name: palbociclib) in combination with letrozole improved real-world progression-free survival (rwPFS) and overall survival (OS) compared with letrozole alone. These findings represent the first comprehensive comparative effectiveness analysis of survival outcomes for a CDK4/6 inhibitor in routine clinical practice, and the data have been published in Breast Cancer Research. See details:Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2− metastatic breast cancer in US real-world clinical practice。

Notably, this represents the first large-scale comparative efficacy analysis evaluating the therapeutic benefits of a CDK4/6 inhibitor combined with letrozole versus letrozole monotherapy on progression-free survival (PFS) and overall survival (OS).。

In this observational, retrospective real-world analysis, after balancing baseline demographic and clinical characteristics, the median rwPFS was 20.0 months in the Ibrance plus letrozole group versus 11.9 months in the letrozole group over a median follow-up of approximately 2 years (HR=0.58; 95% CI: 0.49–0.69; p<0.0001). The median OS was not reached in the Ibrance group, whereas it was 43.1 months in the letrozole group (HR=0.66; 95% CI: 0.53–0.82; P=0.0002). These findings indicate that first-line treatment with the Ibrance plus letrozole regimen reduces the risk of disease progression by 42% and the risk of death by 34% compared with letrozole monotherapy.

The analysis also showed that the 2-year overall response rate (ORR) was 78.3% in the Ibrance plus letrozole group and 68.0% in the letrozole group. The benefits in terms of rwPFS and OS were generally consistent across all subgroups, including younger patients (aged 18–50 years) and those with different sites or extent of metastasis.

Pfizer Global Product DevelopmentTumorChris Boshoff, M.D., Chief Development Officer, stated, “Real-world evidence has been integrated into how we innovate and advance care for patients with breast cancer; the data support our randomized”Clinical Trial“With over six years of patient experience, a favorable benefit-risk profile, robust clinical data, and reliable real-world evidence, all findings confirm the strong efficacy of Ibrance in combination with endocrine therapy for the treatment of patients with HR+/HER2- metastatic breast cancer.”

Dr. Angela DeMichele, Professor of Excellence in Breast Cancer and Principal Investigator at the Perelman School of Medicine, University of Pennsylvania, stated, “Real-world evidence is increasingly being used to supplement traditional randomClinical Trialsdata, to better understand the effectiveness of a therapy in routine clinical practice and to inform treatment decisions. The results of this landmark real-world study are consistent with the positive effects I have observed in patients receiving Ibrance combination therapy.”

This retrospective observational analysis utilized data collected from the Flatiron Health de-identified longitudinal database, which comprises patient records from more than 280 community oncology clinics within the Flatiron network and collaborations with major academic cancer centers across the United States. This real-world cohort included over 1,400 female patients with HR+/HER2− metastatic breast cancer (mBC) and any degree of visceral involvement. Safety data were not collected as part of the analysis.

The data from this real-world analysis are consistent with the available data from the Phase 3 PALOMA-2 trial, which evaluated Ibrance plus letrozole versus placebo plus letrozole as initial endocrine therapy for postmenopausal women with HR+/HER2- metastatic breast cancer (mBC). However, this observational analysis differs from randomized clinical trials in several aspects. These studies had different endpoints, and real-world observational studies have inherent limitations, including lack of randomization, lack of uniform timing or types of clinical assessments, and challenges associated with missing data. PALOMA-2 randomizedClinical TrialOS data are being collected but are not yet mature.

Ibrance is a first-in-class oral targeted CDK4/6 inhibitor that selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), restoring cell cycle control and blockingTumorCell Proliferation. Dysregulation of the cell cycle is a hallmark of cancer, and CDK4/6 are overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 are key regulators of the cell cycle, triggering the transition from the growth phase (G1 phase) to the DNA synthesis phase (S phase). In estrogen receptor-positive (ER+) breast cancer, CDK4/6 overactivity is highly prevalent, as CDK4/6 are key downstream targets of ER signaling. Preclinical data demonstrate that dual inhibition of CDK4/6 and ER signaling has a synergistic effect and can inhibit the growth of G1-phase ER+ breast cancer cells.

Ibrance is the first CDK4/6 inhibitor launched globally, initially approved in February 2015. To date, it has been approved in more than 90 countries worldwide for first-line and second-line treatment of HR+/HER2- breast cancer. In April 2019, Ibrance received U.S.FDAApproved as the first and only CDK4/6 inhibitor for use in combination with an aromatase inhibitor as first-line therapy for male patients with HR+/HER2- metastatic breast cancer. In the United States, Ibrance is indicated for the treatment of adult patients with HR+/HER2- advanced or metastatic breast cancer: (1) in combination with an aromatase inhibitor as initial endocrine therapy for postmenopausal women or men; (2) in combination with fulvestrant for patients who have experienced disease progression following endocrine therapy.

In 2020, global sales of Ibrance reached $5.392 billion, making it the best-selling CDK4/6 inhibitor worldwide. However, competition in this field has become increasingly intense. Novartis’ Kisqali achieved sales of $687 million in 2020, representing a 45% increase. As a latecomer to the sector—the third CDK4/6 inhibitor to be launched—Eli Lilly’s Verzenio surpassed Novartis’ Kisqali, with 2020 sales reaching $913 million, marking a substantial 57% growth. (Bioon.com)

Original Source: Real-World Evidence Supports Effectiveness of First-line IBRANCE® (palbociclib) Combination Therapy in HR+, HER2- Metastatic Breast Cancer