PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2– advanced breast cancer (ABC).
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.507
ISSN1527-7755
AutoresRichard S. Finn, Miguel Martín, Hope S. Rugo, Stephen E. Jones, Seock‐Ah Im, Karen A. Gelmon, Nadia Harbeck, O. N. Lipatov, Janice M. Walshe, Stacy Moulder, Eric Gauthier, Dongrui R. Lu, Sophia Randolph, Véronique Dièras, Dennis J. Slamon,
Tópico(s)Advanced Breast Cancer Therapies
Resumo507 Background: Hormonal therapy (HT) is the mainstay for patients (pts) with ER+ BC. P, a cyclin-dependent kinase 4/6 inhibitor, blocks growth of ER+/HER2– BC preclinical models. In PALOMA-1, an open-label Ph 2 trial, addition of P to L improved median PFS vs L alone (20.2 months [mo] vs 10.2 mo) in pts with first-line ER+/HER2– ABC with acceptable safety, leading to accelerated FDA approval. PALOMA-2 is a randomized double-blind Ph 3 trial designed to confirm these results. Methods: 666 postmenopausal pts with no prior systemic therapy for ABC were randomized 2:1 to receive P (oral 125 mg/d; 3 wks on/1 wk off) + L (2.5 mg/d continuously) or PLB + L every 28 days until disease progression, consent withdrawal or death. Pts were stratified by disease site, disease-free interval from end of (neo)adjuvant therapy, and prior HT (yes/no). Primary endpoint: investigator-assessed PFS; key secondary endpoints: overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR=CR + PR + SD ≥24 wks), patient-reported outcomes and safety. Tumor assessments were every 12 wks. 347 events were needed with 90% power to detect a hazard ratio (HR) ≤0.69 in favor of P+L (1-sided α=0.025). Results: By 26 Feb 2016, 331 PFS events occurred. Baseline characteristics were well balanced. Median PFS was 24.8 mo (P+L) vs 14.5 mo (PLB+L) (HR=0.58 [0.46–0.72], P<0.000001). ORR was improved with P+L (42.1% vs 34.7%, P=0.031; 55.3% vs 44.4% in pts with measurable disease [P=0.013]). CBR was 84.9% vs 70.3% (P<.0001). Common adverse events (AEs; all grades) with P+L vs PLB+L were neutropenia (79.5% vs 6.3%), fatigue (37.4% vs 27.5%), nausea (35.1% vs 26.1%), arthralgia (33.3% vs 33.8%) and alopecia (32.9% vs 15.8%). Most common severity seen was G3 for neutropenia (56.1%) and G1 for the other AEs. Febrile neutropenia was seen only with P+L (2.5%). Permanent discontinuation due to AEs was 9.7% (P+L) vs 5.9% (PLB+L). OS data are immature; final OS analysis is pending. Conclusion: PALOMA-2 expands and confirms the significant clinical benefit and safety of P+L in ER+/HER2– ABC pts who had not received prior systemic therapy for their advanced disease. Clinical trial information: NCT01740427.
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