Dataset Information

Palbociclib combined with endocrine therapy in heavily pretreated HR⁺/HER2^- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

ABSTRACT: Background: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR⁺/HER2^-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017.

Patients and methods: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR⁺/HER2^- mBC who had progressed on ?4 treatments for advanced disease were eligible.

Results: A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ?6 months; HR 1.93, 95% CI 1.37-2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia.

Conclusions: Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.

SUBMITTER: Manso L

PROVIDER: S-EPMC7695980 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Palbociclib combined with endocrine therapy in heavily pretreated HR<sup>+</sup>/HER2<sup>-</sup> advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

Manso Luis L Hernando Cristina C Galán María M Oliveira Mafalda M Cabrera Miguel A MA Bratos Raquel R Rodríguez César A CA Ruiz-Borrego Manuel M Blanch Salvador S Llombart-Cussac Antonio A Delgado-Mingorance Juan I JI Álvarez-Busto Iñaki I Gallegos Isabel I González-Cortijo Lucía L Morales Serafín S Aguirre Elena E Hernando Blanca A BA Ballesteros Ana A Alés-Martínez José E JE Reboredo Cristina C Oltra Amparo A González-Cao María M Santisteban Marta M Malón Diego D Echeverría Isabel I García-Garre Elisa E Vega Estela E Servitja Sònia S Andrés Raquel R Robles Carlos E CE López Rafael R Galve Elena E Echarri María J MJ Legeren Marta M Moreno Fernando F

Breast (Edinburgh, Scotland) 20201113

<h4>Background</h4>This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR<sup>+</sup>/HER2<sup>-</sup>) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017.<h4>Patients and methods</h4>Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR<sup>+</sup>/HER2<sup>-</sup> ...[more]

PMID: 33242755

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Project description:PurposeThe aim of this study was to evaluate the cost-effectiveness of ribociclib compared to palbociclib, both in combination with letrozole, in the first-line treatment of postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (ABC) from the perspective of the Spanish National Health System (NHS).Patients and methodsDisease progression was simulated with a partitioned survival model developed from the parameterization and extrapolation of survival curves of postmenopausal women with HR+/HER2- ABC from clinical trials with ribociclib or palbociclib, both in combination with letrozole. The model was structured on the basis of three health states (progression-free, progressed disease, and death), with a 1-month cycle length and inclusion of subsequent treatments administered for disease progression, over a time horizon of 15 years. Clinical, economic, and quality of life parameters were drawn from clinical trials and the literature. The use of resources and clinical practice in the Spanish setting was validated by a panel of experts. The Spanish NHS perspective was adopted, taking into account exclusively direct health costs from 2017 expressed in Euros. Drug prices used were the reported ex-factory prices. Uncertainty of the parameters and robustness of the results were evaluated using deterministic and probabilistic sensitivity analyses (2,000 iterations).ResultsThis cost-effectiveness analysis showed a greater benefit (0.437 and 0.285 life-years gained [LYGs] and quality-adjusted life years [QALYs] gained, respectively) and a slightly higher cost (€439.86) for ribociclib+letrozole compared to palbociclib+letrozole. The resulting incremental cost-effectiveness and cost-utility ratios were €1,007.69 per LYG and €1,543.62 per QALY gained, respectively. The results of the multiple sensitivity analyses showed limited dispersion of the outcomes, thus corroborating their robustness.ConclusionFrom the NHS perspective, considering the most commonly established willingness-to-pay thresholds in the Spanish setting, ribociclib+letrozole would represent a cost-effective therapeutic option compared to palbociclib+letrozole in the first-line treatment of HR+/HER2- ABC in postmenopausal women.

Project description:BackgroundCyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance.MethodsTissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival.ResultsNovel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C.ConclusionsWe identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET.Trial registrationClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.

Dataset Information

Palbociclib combined with endocrine therapy in heavily pretreated HR⁺/HER2^- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

Publications

Palbociclib combined with endocrine therapy in heavily pretreated HR<sup>+</sup>/HER2<sup>-</sup> advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

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Dataset Information

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

Publications

Palbociclib combined with endocrine therapy in heavily pretreated HR<sup>+</sup>/HER2<sup>-</sup> advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Palbociclib combined with endocrine therapy in heavily pretreated HR⁺/HER2^- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).