This real-world study of patients with hormone receptor–positive, HER2-negative advanced breast cancer treated with a palbociclib-based therapy as either first- or second-line therapy, showed similar safety and efficacy when compared with clinical study results.
The highly selective inhibitor of CDK4/6 palbociclib is indicated for the treatment of hormone receptor–positive, HER2-negative advanced breast cancer, in combination with an aromatase inhibitor or with fulvestrant for patients who have progressed with an aromatase inhibitor, and in premenopausal women with a luteinizing hormone-releasing hormone agonist.
Real-world data suggest that the efficacy of palbociclib-based therapy is highly conserved. Baptiste Porte, PhD, Postdoctoral Fellow, French Institute of Health and Medical Research, Institut Curie, Paris, France, and colleagues reported the Institut Curie experience.
In this retrospective review, all patients with hormone receptor–positive, HER2-negative advanced breast cancer were treated with a palbociclib-based therapy as either first- or second-line therapy for advanced breast cancer between November 2016 and December 2018. Data regarding clinical, biological, and imaging studies were retrieved from an institutional electronic health records system.
The study included 310 menopausal (75.5%) and premenopausal (24.5%) women whose median age was 61.8 years (range, 23.5-92.1 years). Among them, Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 59.7%, 1 in 32.1%, and 2 in 8.2% of patients. For 26.8% of patients, the advanced breast cancer diagnosis was de novo.
In 51.0% of patients there was ≥1 visceral lesions, bone-only lesions found in 30.3% of patients, 28.1% of patients had ≥3 metastatic sites, and none had brain lesions.
Previous treatments were with chemotherapy (49.4%) or with endocrine therapy (60.7%). Among patients who were pretreated with ≥1 endocrine therapies, 51.1% had shown previous sensibility as defined by an absence of recurrence during adjuvant endocrine therapy or during 24 months after its completion or an absence of progression during 6 months after the beginning of an endocrine therapy for a metastatic disease. In the first-line setting, palbociclib was used in 72.6% of patients and in the second-line setting for 27.4% of patients. The initial dose was 125 mg daily (95.2%).
Palbociclib was administered in combination with an aromatase inhibitor (66.8%) or with fulvestrant (33.2%). In 19.7% of patients, a luteinizing hormone-releasing hormone agonist was given. Denosumab was administered to 68.5% of patients with bone lesions. The median follow-up was 20.7 months.
At 12 months from the initiation of palbociclib, 94.5% of the patients were alive.
For patients without previous endocrine therapy, median progression-free survival (PFS) was 23.4 months (95% confidence interval [CI], 21.6-not reached [NR]) and 22.7 months (95% CI, 14.7-NR) for patients who had shown endocrine sensitivity (hazard ratio [HR], 1.2; 95% CI, 0.81-1.77; P = .0027) and 13.4 months (95% CI, 10.7-20.8) for patients who had not shown endocrine sensitivity (HR, 1.88; 95% CI, 1.29-2.73; P = .003).
Although according to their analysis, sensitivity to previous endocrine therapy was a prognostic factor for PFS with the univariate analysis, this was not found with the multivariate analysis. For PFS, 3 independent poor prognostic factors were identified: previous chemotherapy (HR, 1.6; 95% CI, 1.12-2.29; P <.001); initial ECOG performance status 2 (HR, 2.71; 95% CI, 1.55-4.70; P <.001); and ≥3 metastatic sites (HR, 1.61; 95% CI, 1.15-2.26; P <.001).
Hematologic grade 3/4 adverse events were anemia (3.2%), thrombocytopenia (2.9%), leukopenia (43.9%), and neutropenia (72.3%). Infections (16.5%), stomatitis (13.9%), or alopecia (13.9%) were other adverse events observed (all grades). In 29.4% of patients, at least 1 dose reduction occurred, and permanent discontinuation attributed to treatment toxicity was observed in 5.7% of patients.
In this real-world study of patients with hormone receptor–positive, HER2-negative advanced breast cancer, the efficacy and safety data were strikingly similar to previous reports. Thus, palbociclib, when used in combination with hormone therapy, which may be considered a cornerstone treatment of patients with hormone receptor–positive, HER2-negative breast cancer, was strikingly similar to those with metastatic breast cancer.
Source: Porte B, Carton M, Loirat D, et al. Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS10-40.