Palbociclib in Combination with Aromatase Inhibitors in Elderly Patients with Estrogen Receptor–Positive and HER2-Negative Advanced Breast Cancer

The most common treatment subtype of breast cancer is hormone receptor (HR)-positive breast cancer, which accounts for 60% to 65% of all malignant neoplasms of the breast.¹ The estrogen receptor (ER) signaling pathway has been targeted for more than 50 years in the therapy of HR-positive disease.¹ However, a considerable fraction of these malignancies develop new and acquired resistance to hormone blocking, necessitating alternative methods.¹

The PALOMA-2 study confirmed previous findings that palbociclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, plus letrozole, an aromatase inhibitor, results in significantly longer progression-free survival than letrozole alone in postmenopausal women with ER-positive, HER2-negative, advanced breast cancer and adds to the body of evidence supporting the efficacy and safety of CDK4 and CDK6 inhibition as first-line therapy.¹

The introduction of CDK4/6 inhibitors into mainstream clinical practice has altered the way ER-positive, HER2-negative, advanced breast cancer is treated.² However, because the older population makes up a greater percentage of these patients, it is critical to carefully assess the existing evidence in this group, which is underrepresented in clinical studies. When compared with the general population, older individuals in trials are highly selected and have a reduced risk profile, with the gap widening as they get older. As a result, real-world data must be collected to bridge knowledge gaps, consolidate evidence, and inform practitioners who administer CDK4/6 inhibitors to these older patients.²

A national United Kingdom study was designed with the goal of collating a substantially large-scale, real-world data set of patients aged ≥75 years to evaluate the tolerability, efficacy, and secondary care when palbociclib was used in combination with an aromatase inhibitor such as letrozole in the first-line treatment of elderly patients with ER-positive, HER2-negative, advanced breast cancer.² The age-adjusted Charlson Comorbidity Index was utilized to determine the baseline comorbidity burden in this cohort, as well as its impact on therapy and tolerability.²

This was a multicenter retrospective study involving 14 cancer centers from around the United Kingdom.² The qualifying criteria were met by 276 patients. Neutropenia was the most common side effect, followed by fatigue, anemia, and thrombocytopenia. Six (2.2%) patients had febrile neutropenia, 50.7% needed a dose reduction, and 59.3% needed a delay of ≥1 doses. At 24 weeks, the clinical benefit rate was 87%. At 12 months and 24 months, the progression-free survival rates were 75.9% and 64.9%, respectively, and the overall survival rates were 85.1% and 74.0%, respectively.²

Palbociclib was found to be a well-tolerated treatment in older patients with advanced ER-positive, HER2-negative breast cancer, despite their frailty and comorbidity burden, in this large-scale trial.² Geriatric and frailty evaluations can aid in making decisions for these patients.

References

1. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375:1925-1936.
2. El Badri S, Tahir B, Balachandran K, et al. Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: a real-world multicentre UK study. Breast. 2021;60:199-205.