Clinical trialPhase 3Breast cancer

Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer

N Engl J Med · 2015521 patients

Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, et al. N Engl J Med. 2015. 373:209-219

A newer report of this study has been published: Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer (2018)

Study type: Clinical trial
Study name: PALOMA3
Phase: Phase 3
Design: Randomised, placebo-controlled phase 3 trial with 2:1 allocation (palbociclib + fulvestrant versus placebo + fulvestrant)
Sample size: 521 patients
Source: N Engl J Med · 2015
Trial registration: NCT01942135

In plain words

This study was done in 521 women with advanced hormone receptor-positive breast cancer whose disease had progressed despite earlier hormone treatment. Adding the drug palbociclib to fulvestrant lengthened the median time until the disease progressed from 3.8 months to 9.2 months. The most common side effect of this combination was a marked drop in white blood cells (neutropenia), but few patients stopped treatment because of side effects.

Key results

9.2 months

Median PFS — palbociclib + fulvestrant

95% CI: 7.5 to not estimable

3.8 months

Median PFS — placebo + fulvestrant

95% CI: 3.5 to 5.5

0.42

Hazard ratio for disease progression or death

95% CI: 0.32 to 0.56; P<0.001

62.0% vs 0.6%

Grade 3 or 4 neutropenia

Palbociclib + fulvestrant vs placebo + fulvestrant

2.6% vs 1.7%

Discontinuation because of an adverse event

Palbociclib vs placebo

Drugs in this study:Abemaciclib (Verzenio)Fulvestrant (Faslodex)Goserelin (Zoladex)Letrozole (Femara)Palbociclib (Ibrance)Anastrozole (Arimidex)Ribociclib (Kisqali)

Dose and schedule cards

Hormone therapy + CDK4/6 inhibitor (PALOMA-2, MONALEESA-2, MONARCH 3; after progression: PALOMA-3)

Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapyOn the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapy

Drug	Dose	Route	Schedule
One of three drugs
Palbociclib	125 mg once daily	Oral	Days 1–21
Ribociclib	600 mg once daily	Oral	Days 1–21
Abemaciclib	150 mg twice daily	Oral	Continuous
Combined with
Letrozole (or anastrozole 1 mg)	2.5 mg once daily	Oral	Continuous
Or combined with
Fulvestrant	500 mg (two 5-mL injections, one in each buttock)	IM, slowly	Days 1, 15 and 29, then monthly

Cycle length: Palbociclib and ribociclib: every 28 days; abemaciclib continuous
Duration: Until progression or unacceptable toxicity

Ribociclib: reduce to 400 mg and then 200 mg. Abemaciclib: monotherapy 200 mg twice daily.

On the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Palbociclib + fulvestrant

Palbociclib 125 mg orally daily for 3 weeks followed by 1 week off (28-day cycle) + fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then on day 1 of each 28-day cycle; pre-‎ or perimenopausal women received goserelin starting at least 4 weeks before the start and throughout the study. Treatment until progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal (2:1 randomisation).

2Placebo + fulvestrant

Placebo on the same schedule + fulvestrant 500 mg (days 1 and 15 of cycle 1, then day 1 every 28 days); goserelin for pre-‎ or perimenopausal women.

Source of the regimen details: ClinicalTrials.gov NCT01942135 and the FDA label for Ibrance (DailyMed, section 14, PALOMA-3)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with hormone receptor-positive, HER2-negative (human epidermal growth factor receptor 2) advanced breast cancer that had relapsed or progressed during previous endocrine therapy.

Endpoints

Primary endpoint: investigator-assessed progression-free survival (PFS). Secondary endpoints: overall survival, objective response, clinical benefit rate, patient-reported outcomes and safety. A prespecified interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death.

Safety and side effects

The most common grade 3 or 4 adverse events in the palbociclib + fulvestrant group: neutropenia (62.0% vs 0.6% in the placebo + fulvestrant group), leucopenia (25.2% vs 0.6%), anaemia (2.6% vs 1.7%), thrombocytopenia (2.3% vs 0%) and fatigue (2.0% vs 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation because of adverse events was 2.6% with palbociclib and 1.7% with placebo.

Clinical significance and place in guidelines

Based on the abstract, in patients with hormone receptor-positive metastatic breast cancer that had progressed on previous endocrine therapy, adding palbociclib to fulvestrant prolonged progression-free survival compared with fulvestrant alone. The status of drug approvals and clinical guideline recommendations should be checked separately in up-to-date sources.

Limitations

The primary endpoint was investigator-assessed. The results reported in the abstract come from a prespecified interim analysis, and the upper limit of the confidence interval for median progression-free survival in the palbociclib group was not estimable. Overall survival and other secondary endpoint results are not reported in the abstract. The study was funded by Pfizer.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.