|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
A clinically meaningful long-term improvement in overall survival (OS) was seen with palbociclib plus fulvestrant in patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2-) advanced breast cancer, according to the research presented by Massimo Cristofanilli, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, Illinois, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Palbociclib is an oral, first-in-class, cyclin-dependent kinase (CDK) 4/6 selective inhibitor that is approved for HR+/HER2- advanced breast cancer.
In a randomized, double-blind, placebo-controlled, phase 3 PALOMA-3 trial (ClinicalTrials.gov Identifier: NCT01942135), palbociclib plus fulvestrant significantly improved OS compared with fulvestrant plus placebo (median OS, 34.9 vs 28.0 months; hazard ratio [HR], 0.814; 95% CI, 0.644-1.029; 1-sided P =.0429) in patients with HR+/HER2- advanced breast cancer after a median follow-up of 44.8 months.
Dr Cristofanilli reported the final analysis of 521 patients (75% of the study population) after a median follow-up of 73.3 months. The study included 521 women with HR+/HER2- breast cancer whose disease progressed on prior endocrine therapy. These patients were randomly assigned 2:1 to palbociclib plus fulvestrant or fulvestrant plus placebo. The primary endpoint was progression-free survival (PFS) and the key secondary endpoint was OS.
With more than 6 years of follow-up, there was continued improvement of OS with palbociclib plus fulvestrant (HR, 0.806; 95% CI, 0.654-0.994; 1-sided nominal P =.0221). The 5-year OS rate for the palbociclib plus fulvestrant and fulvestrant plus placebo groups were 23.3% (95% CI, 18.7-28.2) and 16.8% (95% CI, 11.2-23.3), respectively.
The prolonged OS benefit with palbociclib plus fulvestrant was seen in most subgroups but not in women who were endocrine resistant or had prior chemotherapy.
Twenty women (7.5%) in the palbociclib plus fulvestrant arm and 32 women (22.2%) in the fulvestrant plus placebo arm had received a post-study CDK 4/6 inhibitor. At the end of treatment,circulating tumor (ctDNA) DNA analysis was performed to assess the effect of ESR1, PIK3CA, and TP53 gene mutations on OS.
The OS benefit with palbociclib plus fulvestrant vs fulvestrant plus placebo was maintained regardless of the status of ESR1, PIK3CA, and TP53 gene mutations as detected by ctDNA polymerase chain reaction sequencing.
“Our findings support the continued use of palbociclib plus fulvestrant as a standard of care in patients with HR+/HER2- advanced breast cancer,” said Dr Cristofanilli.
Disclosure: This research was supported by Pfizer Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Cristofanilli M, Rugo HS, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2–negative (HER2) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021;39:(suppl 15; abstr 1000). doi:10.1200/JCO.2021.39.15_suppl.1000