Phase 3
Completed N=521
Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)
Source: ClinicalTrials.gov NCT01942135 ↗Enrolled (actual)
521
Serious AEs
21.5%
Results posted
May 2016
Primary outcomePrimary: Progression-Free Survival (PFS) as Assessed by the Investigator — 9.2; 3.8 months — p=<0.000001
◆ Published Evidence
Established
34citations · ~7 / year
Prognostic Factors for Overall Survival in Patients with Hormone Receptor-Positive Advanced Breast Cancer: Analyses From PALOMA-3.
Summary
The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the superiority of palbociclib in combination with fulvestrant (Faslodex®) over fulvestrant alone in prolonging PFS in women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy. The safety between the two treatment arms will also be compared. During study treatment, pre- and perimenopausal women must be receiving therapy with the LHRH agonist goserelin (Zoladex® or generic).
Linked Publications (5)
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Prognostic Factors for Overall Survival in Patients with Hormone Receptor-Positive Advanced Breast Cancer: Analyses From PALOMA-3.
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Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib.
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Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3.
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Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials.
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Effect of palbociclib plus endocrine therapy on time to chemotherapy across subgroups of patients with hormone receptor‒positive/human epidermal growth factor receptor 2‒negative advanced breast cancer: Post hoc analyses from PALOMA-2 and PALOMA-3.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-Free Survival (PFS) as Assessed by the Investigator |
9.2; 3.8 | <0.000001 sig |
| SECONDARY Overall Survival (OS)-Number of Participants Who Died |
201; 109 | — |
| SECONDARY Overall Survival (OS) |
34.9; 28.0 | =0.0429 sig |
| SECONDARY Survival Probabilities at Year 1, Year 2, and Year 3 |
85.5; 84.8; 65.3; 57.3; 49.6; 40.8 | — |
| SECONDARY Objective Response (OR) |
21.0; 8.6 | 0.0001 sig |
| SECONDARY Duration of Response (DR) |
10.4; 9.0 | — |
| SECONDARY Clinical Benefit Response (CBR) |
66.3; 39.7 | <0.0001 sig |
| SECONDARY Observed Plasma Trough Concentration (Ctrough) for Palbociclib |
70.70; 75.29 | — |
| SECONDARY Ctrough for Fulvestrant |
11.75; 9.31; 9.90; 7.60 | — |
| SECONDARY Ctrough for Goserelin |
295.1; 302.5; 344.8; 288.5 | — |
| SECONDARY Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores |
-0.9; -4.0; -0.7; -1.7; -1.8; -3.7 | 0.0313 sig |
| SECONDARY Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores |
1.8; 3.3; 1.7; 4.2; -3.3; 2.0 | 0.3200 |
| SECONDARY Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores |
1.9; -0.3; -1.1; -0.4; -5.2; -6.6 | 0.1386 |
| SECONDARY Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores |
3.8; 3.4; -2.2; -1.3; -2.2; -2.0 | 0.7273 |
| SECONDARY Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores |
0.006; -0.031 | 0.0308 sig |
| SECONDARY Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale |
-1.8; -2.6 | 0.5523 |
| SECONDARY Time to Deterioration (TTD) |
1.9; 1.0; 8.0; 2.8 | <0.001 sig |
| SECONDARY Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) |
98.8; 93.6; 22.6; 19.2; 80.6; 26.7 | — |
| SECONDARY Participants With Shifts From CTCAE Grade ≤2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Hematology Results |
16; 3; 1; 0; 239; 1 | — |
| SECONDARY Participants With Shifts From CTCAE Grade ≤2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Chemistry Results |
10; 1; 2; 2; 13; 7 | — |
Eligibility Criteria
Inclusion Criteria
- Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
- Confirmed diagnosis of HR+/HER2- breast cancer
- Any menopausal status
- Progressed within 12 months from prior adjuvant or progressed within 1 month from prior advanced/metastatic endocrine breast cancer therapy
- On an LHRH agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization.
- Measurable disease defined by RECIST version 1.1, or bone-only disease
- Eastern Cooperative Oncology Group (ECOG) PS 0-1
- Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures
- Patient must agree to provide tumor tissue from metastatic tissue at baseline
Exclusion Criteria
- Prior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathway
- Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases
- Major surgery or any anti-cancer therapy within 2 weeks of randomization
- Prior stem cell or bone marrow transplantation
- Use of potent CYP3A4 inhibitors or inducers
Data sourced from ClinicalTrials.gov (NCT01942135) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.