Abstract
Palbociclib is a cyclin‐dependent kinase 4/6 inhibitor indicated for treatment of hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer in combination with endocrine therapy. We investigated the efficacy and safety of palbociclib in patients enrolled in North America during two‐phase 3 trials: PALOMA‐2 (n = 267, data cutoff: May 31, 2017) and PALOMA‐3 (n = 240, data cutoffs: April 13, 2018, for overall survival, October 23, 2015, for all other outcomes). In PALOMA‐2, treatment‐naïve postmenopausal patients with advanced breast cancer were randomized 2:1 to palbociclib (125 mg/d; 3 weeks on/1 week off [3/1]) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. In PALOMA‐3, patients who progressed on prior endocrine therapy were randomized 2:1 to palbociclib (125 mg/d; 3/1) plus fulvestrant (500 mg, per standard of care) or placebo plus fulvestrant; pre/perimenopausal patients received ovarian suppression with goserelin. Palbociclib plus endocrine therapy prolonged median progression‐free survival vs placebo plus endocrine therapy in North American patients (PALOMA‐2: 25.4 vs 13.7 months, hazard ratio, 0.54 [95% CI, 0.40–0.74], P < .0001; PALOMA‐3: 9.9 vs 3.5 months, hazard ratio, 0.52 [95% CI, 0.38–0.72], P < .0001). Objective response and clinical benefit response rates were greater with palbociclib vs placebo in North American patients in both trials. While overall survival data are not yet mature for PALOMA‐2, median overall survival was increased in PALOMA‐3 (32.0 vs 24.7 months, hazard ratio, 0.75 [95% CI, 0.53–1.04]), though this did not reach statistical significance (P = .0869). Safety profiles in North American patients were similar to those of the overall populations; neutropenia was the most common treatment‐emergent adverse event. No new safety signals were observed. In summary, palbociclib plus endocrine therapy is an effective treatment option for North American women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.
Highlights
Breast cancer is the most common cancer diagnosis in women from developed countries.[1,2] Incidence and mortality vary across coun‐ tries due partly to differences in screening, lifestyle, and effects of race and ethnicity on treatment response.[1,3,4] Understanding re‐ gional differences is critical to optimizing care
This analysis compared the efficacy of palbociclib plus endocrine therapy (ET) with that of placebo plus ET in a subset of the intent‐to‐treat (ITT) population enrolled in the United States and Canada, regardless of ethnicity
Updated data for North American patients from the PALOMA‐3 trial indicated that overall survival (OS) was longer with palbociclib vs placebo (32.0 vs 24.7 months, hazard ratios (HR), 0.75 [95% confidence intervals (CIs), 0.53– 1.04]), P = .0869]), similar to results seen in the overall population (34.9 vs 28.0 months, HR, 0.81 [95% CI, 0.64–1.03]), P = .09]).[20]
Summary
Breast cancer is the most common cancer diagnosis in women from developed countries.[1,2] Incidence and mortality vary across coun‐ tries due partly to differences in screening, lifestyle, and effects of race and ethnicity on treatment response.[1,3,4] Understanding re‐ gional differences is critical to optimizing care. Breast cancer is the most common cancer diagnosis in women from developed countries.[1,2]. Incidence and mortality vary across coun‐ tries due partly to differences in screening, lifestyle, and effects of race and ethnicity on treatment response.[1,3,4]. Understanding re‐ gional differences is critical to optimizing care. In the United States (US), approximately 266,000 new cases of breast cancer and 41,000 deaths occur annually.[5]. For women with advanced breast cancer (ABC), 5‐year survival rates are only 27%.5. 60% to 70% of patients with ABC have hormone receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) tumors.[6,7]. In this setting, endocrine therapy (ET) is the preferred option for patients who are not symptomatic or in visceral cri‐ sis.[2,8]. 60% to 70% of patients with ABC have hormone receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) tumors.[6,7] In this setting, endocrine therapy (ET) is the preferred option for patients who are not symptomatic or in visceral cri‐ sis.[2,8] Recent advances have enabled the development of combination strategies to delay progression and limit resistance to monotherapy, including targeting the cyclin‐dependent kinase (CDK) 4/6 pathway.[9-12]
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