Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

Varella, Leticia; Eziokwu, Akaolisa Samuel; Jia, Xuefei; Kruse, Megan; Moore, Halle C. F.; Budd, G. Thomas; Abraham, Jame; Montero, Alberto J.

doi:10.1007/s10549-019-05176-1

Cited by 54 publications

(74 citation statements)

References 13 publications

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“…With a longer follow-up, subsequent large US and international studies have shown similar PFS data and have suggested an OS benefit [13,14]. Other, more limited studies, were in line with those results [26][27][28][29][30][31][32][33].…”

Section: Discussionsupporting

confidence: 58%

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

et al. 2020

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Background Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience. Patients and methods We retrospectively reviewed all patients with HR + HER2- ABC treated with a palbociclib-based therapy as first or second line for ABC, with an initial prescription from November 2016 to December 2018. Clinical, laboratory and imaging data were retrieved from electronic records. Data lock was December 31st, 2019. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. Results We included 310 consecutive patients. Median age was 61.8 years old. Palbociclib was prescribed in first line in 225 patients (72.6%). Before palbociclib-based therapy initiation, 122 patients (39.3%) were endocrine naive, 96 (31.0%) endocrine sensitive and 92 (29.7%) endocrine resistant. Median follow-up was 20.7 months. Median progression free survival (PFS) was 23.4 months (95%CI: 21.6-NR) in endocrine naive patients, 22.7 months (95%CI: 14.7-NR) in endocrine sensitive, and 13.4 months (95%CI: 10.7–20.8) in endocrine resistant. At 12 months from the initiation of palbociclib, 94.5% of patients were alive. By multivariate analysis, poor prognosis factors for PFS were identified in the endocrine naive/sensitive population: initial ECOG status 2, previous endocrine therapy for ABC, 3 metastatic sites or more. Toxicity profile was similar to previously published data. Conclusion In a non-selected population of patients with HR + HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported.

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Section: Discussionsupporting

confidence: 58%

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

et al. 2020

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“…Results from those analyses are highly dependent on the quality of the data that is used [ 12 ]. With regard to CDK4/6i therapies, there have been reports from an extended access program in heavily pretreated patients [ 13 ], from a retrospective anaylsis within a U.S. hospital system [ 14 ], and a retrospective market research anaylsis [ 15 ]. In addition to those analyses our registry captures all patients prospectively and might be able to provide data, how CDK4/6i were introduced in the treatment of ABC as well as prospectively captured survival data.…”

Section: Introductionmentioning

confidence: 99%

Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany

et al. 2020

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Purpose Treatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor–positive, HER2-negative (HR + HER2–) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported. Methods The PRAEGNANT registry was used to identify advanced HR + HER2– BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed. Results CDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy. Conclusions In clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET.

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“…AST elevation was not observed in previous studies of SHetA2 [17], and there were no effects of any drug treatments on animal body weights, or on organ-to-body weight ratios, which reduces concern regarding potential toxicity. The most common side effect requiring dose-reduction of palbociclib is neutropenia [20,34]. Our calculated DRIs suggest that, when combined with SHetA2, lower doses of palbociclib could be used to achieve the same level of anti-cancer activity with reduced risk of developing palbociclib-induced neutropenia.…”

Section: Discussionmentioning

confidence: 91%

“…Preclinical studies conducted by the National Cancer Institute found the no observed adverse event level (NOAEL) of SHetA2 in dogs to be >25-fold higher than the effective dose in cancer prevention and treatment studies [17][18][19]. The most common adverse event associated with palbociclib treatment is hematologic toxicity, mostly mild to moderate neutropenia, which can be reversed with dose reduction [20].…”

Section: Introductionmentioning

confidence: 99%

Complementary Targeting of Rb Phosphorylation and Growth in Cervical Cancer Cell Cultures and a Xenograft Mouse Model by SHetA2 and Palbociclib

Kennedy

Rai

Isingizwe

et al. 2020

Cancers

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Cervical cancer is caused by high-risk human papillomavirus (HPV) types and treated with conventional chemotherapy with surgery and/or radiation. HPV E6 and E7 proteins increase phosphorylation of retinoblastoma (Rb) by cyclin D1/cyclin dependent kinase (CDK)4/6 complexes. We hypothesized that cyclin D1 degradation by the SHetA2 drug in combination with palbociclib inhibition of CDK4/6 activity synergistically reduces phosphorylated Rb (phospho-Rb) and inhibits cervical cancer growth. The effects of these drugs, alone, and in combination, were evaluated in SiHa and CaSki HPV-positive and C33A HPV-negative cervical cancer cell lines using cell culture, western blots and ELISA, and in a SiHa xenograft model. Endpoints were compared by isobolograms, ANOVA, and Chi-Square. In all cell lines, combination indexes documented synergistic interaction of SHetA2 and palbociclib in association SHetA2 reduction of cyclin D1 and phospho-Rb, palbociclib reduction of phospho-Rb, and enhanced phospho-Rb reduction upon drug combination. Both drugs significantly reduced phospho-Rb and growth of SiHa xenograft tumors as single agents and acted additively when combined, with no evidence of toxicity. Dilated CD31-negative blood vessels adjacent to, or within, areas of necrosis and apoptosis were observed in all drug-treated tumors. These results justify development of the SHetA2 and palbociclib combination for targeting phospho-Rb in cervical cancer treatment.

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Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

Cited by 54 publications

References 13 publications

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany

Complementary Targeting of Rb Phosphorylation and Growth in Cervical Cancer Cell Cultures and a Xenograft Mouse Model by SHetA2 and Palbociclib

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