Palbociclib Plus Endocrine Therapy vs Capecitabine for HER2-Negative Metastatic Breast Cancer

Postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer treated with palbociclib plus endocrine therapy experienced no statistically significant improvement in overall survival (OS) vs treatment with capecitabine, according to the PEARL study.

“The use of chemotherapy in hormone-sensitive [metastatic breast cancer] patients is very common after [endocrine therapy] failure. Capecitabine, an oral drug, is well tolerated and active in patients with [metastatic breast cancer] and one of the best options in patients with progression to prior therapies,” wrote lead author Miguel Martin, MD, PhD, and coauthors.

From March 2014 to July 2018, the phase 3 trial enrolled 601 postmenopausal patients from 37 sites in 4 countries. Patients were randomized in a 1:1 ratio to treatment with capecitabine or one of two cohorts receiving palbociclib plus endocrine therapy of either exemestane or fulvestrestat, respectively. The primary outcome was OS, measured in Cohort 2 (fulvestrestat), the wild-type ESR1 population, and the overall population.

After a median follow-up period of 28 (range, 0 to 54.2) months for cohort 2, OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio [aHR], 1.10; 95% confidence interval [CI], 0.81 to 1.50; P = .550).

For the ESR1 wild-type population, the median follow-up period was 30.3 (0 to 79.7) months. Median OS for this arm was 37.2 months for palbociclib plus endocrine therapy vs 34.8 months for capecitabine (aHR, 1.06; 95% CI, 0.81 to 1.37; P = .683). For the overall population, the median follow-up was 28.2 (0 to 79.7) months with a median OS of 32.6 months for palbociclib plus endocrine therapy and 30.9 months for capecitabine (P = .995).

Palbociclib plus endocrine therapy yielded no systemic superiority of OS vs capecitabine in any subgroup. No new treatment related adverse events were observed.

“In hormone receptor-positive/HER2-negative [metastatic breast cancer] patients with prior [aromatase inhibitor] therapy, capecitabine and palbociclib plus [endocrine therapy] were associated with the same OS,” explained Dr Zielinski and colleagues, concluding, “from our point of view, the choice of one over another therapy should depend on other considerations, such as cost of therapy, tolerability and quality of life.”

Source:

Martín M, Zielinski C, Ruiz-Borrego M, et al. Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study. Eur J Cancer. 2022;168:12-24. doi:10.1016/j.ejca.2022.03.006