Palbociclib + Endocrine Therapy vs Capecitabine for HR-Positive HER2-Negative Breast Cancer: PEARL
- 3 years ago
Although patients with hormone receptor (HR)-positive, HER2-negative, aromatase inhibitor–resistant metastatic breast cancer maintained quality of life for a longer time following treatment with palbociclib plus either exemestane or fulvestrant than capecitabine, those receiving chemotherapy demonstrated improved progression-free survival and higher response rates compared with the palbociclib-treated patients. Details from the phase III PEARL study were published by Miguel Martín, MD, PhD, in Annals of Oncology.
The authors noted that although palbociclib plus endocrine therapy has become standard treatment for HR-positive, HER2-negative metastatic breast cancer, it had never been directly compared for efficacy with chemotherapy in a phase III trial.
PEARL Methods
Therefore, the investigators conducted the multicenter, phase III randomized PEARL study in patients with HR-positive, HER2-negative metastatic breast cancer who were resistant to aromatase inhibitors. The study comprised two consecutive cohorts.
In cohort 1, 296 patients were randomly assigned 1:1 to palbociclib plus exemestane or capecitabine. Upon emerging evidence that estrogen receptor-1 (ESR1) mutations could induce resistance to aromatase inhibitors, the study was amended to include 305 patients in cohort 2 who were randomly assigned 1:1 to receive palbociclib plus fulvestrant or capecitabine.
Patients in both cohorts were stratified according to disease site, prior sensitivity to endocrine therapy, receipt of prior chemotherapy for metastatic breast cancer, and country of origin. Circulating tumor DNA samples were obtained at baseline for analysis of ESR1 hotspot mutations.
The co-primary endpoints were progression-free survival in cohort 2 patients and progression-free survival in patients having wild-type ESR1 in both cohorts.
Progression-Free Survival
The median follow-up was 13.5 months (range = 0.0–30.7) in cohort 2 and the wild-type ESR1 population, and 18.9 months (range = 0.0–56.3) in cohort 1 and patients with mutated ESR1.
Regarding cohort 1 patients, the median progression-free survival was 7.5 months (95% confidence interval [CI] = 5.7–10.9) with palbociclib/fulvestrant compared to 10.0 months (95% CI = 6.3–12.9) with capecitabine (adjusted hazard ratio [aHR] = 1.13, 95% CI = 0.85–1.50, P = .398).
Patients with wild-type ESR1 demonstrated a median progression-free survival of 8.0 months (95% CI = 6.5–10.9) with palbociclib plus endocrine therapy compared to 10.6 months (95% CI = 7.4–13.0) with capecitabine (aHR = 1.11, 95% CI = 0.87–1.41, P = .404).
Evaluation of efficacy, the secondary endpoint of the study, showed that median progression-free survival in cohort 1 and cohort 2 patients overall was 7.4 months (95% CI = 5.9–9.3) with palbociclib plus endocrine therapy vs 9.4 months (95% CI = 7.5–11.3) with capecitabine (aHR = 1.11, 95% CI = 0.92–1.34, P = .380).
The objective response rate was also higher with capecitabine chemotherapy across treatment a
The authors noted that although palbociclib plus endocrine therapy has become standard treatment for HR-positive, HER2-negative metastatic breast cancer, it had never been directly compared for efficacy with chemotherapy in a phase III trial.
PEARL Methods
Therefore, the investigators conducted the multicenter, phase III randomized PEARL study in patients with HR-positive, HER2-negative metastatic breast cancer who were resistant to aromatase inhibitors. The study comprised two consecutive cohorts.
In cohort 1, 296 patients were randomly assigned 1:1 to palbociclib plus exemestane or capecitabine. Upon emerging evidence that estrogen receptor-1 (ESR1) mutations could induce resistance to aromatase inhibitors, the study was amended to include 305 patients in cohort 2 who were randomly assigned 1:1 to receive palbociclib plus fulvestrant or capecitabine.
Patients in both cohorts were stratified according to disease site, prior sensitivity to endocrine therapy, receipt of prior chemotherapy for metastatic breast cancer, and country of origin. Circulating tumor DNA samples were obtained at baseline for analysis of ESR1 hotspot mutations.
The co-primary endpoints were progression-free survival in cohort 2 patients and progression-free survival in patients having wild-type ESR1 in both cohorts.
Progression-Free Survival
The median follow-up was 13.5 months (range = 0.0–30.7) in cohort 2 and the wild-type ESR1 population, and 18.9 months (range = 0.0–56.3) in cohort 1 and patients with mutated ESR1.
Regarding cohort 1 patients, the median progression-free survival was 7.5 months (95% confidence interval [CI] = 5.7–10.9) with palbociclib/fulvestrant compared to 10.0 months (95% CI = 6.3–12.9) with capecitabine (adjusted hazard ratio [aHR] = 1.13, 95% CI = 0.85–1.50, P = .398).
Patients with wild-type ESR1 demonstrated a median progression-free survival of 8.0 months (95% CI = 6.5–10.9) with palbociclib plus endocrine therapy compared to 10.6 months (95% CI = 7.4–13.0) with capecitabine (aHR = 1.11, 95% CI = 0.87–1.41, P = .404).
Evaluation of efficacy, the secondary endpoint of the study, showed that median progression-free survival in cohort 1 and cohort 2 patients overall was 7.4 months (95% CI = 5.9–9.3) with palbociclib plus endocrine therapy vs 9.4 months (95% CI = 7.5–11.3) with capecitabine (aHR = 1.11, 95% CI = 0.92–1.34, P = .380).
The objective response rate was also higher with capecitabine chemotherapy across treatment a