Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

Wilkie, Jonathan; Schickli, M. Alexandra; Berger, Michael; Lustberg, Maryam B.; Reinbolt, Raquel E.; Noonan, Anne M.; Ramaswamy, Bhuvaneswari; Sardesai, Sagar; VanDeusen, Jeffrey; Williams, Nicole; Stover, Daniel G.; Vargo, Craig

doi:10.1016/j.clbc.2019.06.010

Cited by 32 publications

(45 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that dose reduction was significantly associated with worse PFS. This is in contrast to what has been observed in randomized trials [ 35 , 36 , 37 , 38 ] and some other retrospective studies [ 39 , 40 ]. Upfront dose reduction and subsequent dose reduction due to toxicity could reflect poor patient-related prognostic factors, such as less favourable performance status and comorbidities.…”

Section: Discussioncontrasting

confidence: 97%

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

2021

View full text Add to dashboard Cite

In this analysis, we describe population-based outcomes for first-line treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with an aromatase inhibitor (AI). All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 were included. Patient demographics, tumour and treatment characteristics were collected and described. Survival distributions were estimated using the Kaplan–Meier method. Multivariate analysis (MVA) was constructed to examine associations between potentially prognostic clinical variables and progression-free survival (PFS). In total, 316 patients were included. The median age was 61 years. After a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7–NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45–3.88; p = 0.001) and CDK4/6i dose reduction (HR, 1.51; 95% CI, 1.06–2.16; p = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed, 89% received second-line treatment. Median time to progression on second-line chemotherapy was 9.0 (5.8–17.6) months, and median time to progression on second-line hormonal therapy +/− targeted agent was 4.0 (3.4–8.6) months (p = 0.012). CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favourable PFS and early OS outcomes.

show abstract

Section: Discussioncontrasting

confidence: 97%

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

2021

View full text Add to dashboard Cite

show abstract

“…20,21 The effectiveness of palbociclib as a first-line therapy in our study was similar to that reported in a previous retrospective study by Varella et al 22 (median PFS: 15.1 months). However, Wilkie et al 23 reported a more prolonged median time-to-treatment failure (26.1 months) for patients treated with palbociclib plus aromatase inhibitor as a first-line therapy than that observed in our study. This difference may be attributed to the fact that liver metastasis results in poor outcomes, and the number of patients who had liver metastases in this study (50% of the first-line therapy patients) was greater than that of the previous study (10%).…”

Section: Discussioncontrasting

confidence: 85%

Real-World Outcomes of Treating Advanced Breast Cancer Patients With Palbociclib: A Multicenter Retrospective Cohort Study in Japan—The KBCOG-14 Study

Odan

Kikawa

Matsumoto

et al. 2020

Breast Cancer�(Auckl)

View full text Add to dashboard Cite

Background: Clinical studies have shown that palbociclib improves progression-free survival in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) patients with advanced breast cancer (ABC). However, there are insufficient data on its use in a real-world setting in Japan. The aim of this study was to investigate the effectiveness, predictive factors, and safety of palbociclib among Japanese patients in routine clinical practice. Methods: Between December 1, 2017, and April 30, 2019, we recruited patients from 9 hospitals and retrospectively evaluated the data on HR+/HER2− patients with ABC who received palbociclib for at least 1 week. The correlation between time-to-treatment discontinuation (TTD) and clinical background was investigated via univariate and multivariate analyses using Cox hazards models. Results: A total of 177 women were available for analysis. Of these patients, 58 (33%) patients were treated with palbociclib with an aromatase inhibitor and 117 (66%) patients were treated with palbociclib and a selective estrogen receptor degrader. Approximately three-fourths of the patients (n = 130, 73%) received palbociclib as third- or later-line therapy. One-third of the patients had 3 or more metastatic sites (n = 59, 33%), and one-third of the patients had liver metastasis (n = 59, 33%). The median follow-up duration at the time of data cutoff was 8.9 months, the median TTD was 6.3 months, and the median overall survival was not reached. Liver metastasis (hazard ratio [HR]: 1.54 [95% confidence interval {CI}: 1.03-2.27]), high serum lactate dehydrogenase (LDH) level (>300 U/L) (HR: 2.58 [95% CI: 1.49-4.26]), and high neutrophil-to-lymphocyte ratio (NLR) (⩾3.0) (HR: 1.76 [95% CI: 1.13-2.69]) were significantly associated with shorter TTD. The most common hematologic adverse event was neutropenia, which occurred in 93% of the patients. Conclusion: Based on the results of the pivotal phase 3 trials, the median TTD recorded in this study was shorter than expected. Our results suggest that liver metastasis, serum LDH level, and NLR may be predictive factors for HR+/HER2− ABC treatment outcomes.

show abstract

“…However our results indicate that dose reduction of ribociclib is safe, and the results ts preliminary results from MONALEESA trials subgroup analysis [27]. Similar results have previously been published concerning the CDK4/6 inhibitor Palbociclib [28]. Still, caution is advised in concluding that ribociclib in lower doses (200-400mg) have equal (or better) e cacy than full dosage (600mg).…”

Section: Discussionsupporting

confidence: 87%

Dose Modifications of Ribociclib and Endocrine Therapy for Treatment of ER+ HER2- metastatic Breast Cancer 

Kristensen

Thomsen

Berg

et al. 2021

Preprint

View full text Add to dashboard Cite

Purpose: Treatment for estrogen receptor positive (ER+), human epidermal receptor 2 negative (HER2-) metastatic breast cancer (MBC) has improved with the approval of CDK 4/6 inhibitors. Clinical trials with the CDK4/6 inhibitor ribociclib, suggest that between 35% to 57.5% of the patients experience a dose reduction during treatment. Information on the possible consequences of dose reduction concerning efficacy is needed. Methods: A retrospective cohort study on patients with ER+ HER2- MBC from three Danish oncology departments. Data on tolerability and progression-free survival were collected from electronic health records. Results: 128 patients with ER+ HER2- MBC who initiated ribociclib treatment between 1st January 2018 to 31st March 2020 were included in our analysis. Of these patients, 48.4% required one or more dose reductions. Overall median PFS was 19.2 months (CI-95%: 14.3-NR). Patients with one or more dose reductions did not have decreased median PFS (19.2 months, CI-95%: 14.3-NR compared to 12.2 months, CI-95%: 7.3-NR. p=0.078). Frequency of adverse events were as previously reported, with grade III and IV neutropenia occurring in 45.3% and 7% of patients, respectively. Patients treated with fulvestrant versus an aromatase inhibitor and patients with lymph node involvement at baseline had lower odds of requiring dose reduction (ORa = 0.30, CI-95%: 0.18-0.89 & ORa = 0.41, CI-95%: 0.12-0.73, respectively). Conclusion: Our results indicate that dose reduction of ribociclib is safe and do not compromise the efficacy of the treatment. Furthermore, the study supports translation of results from the MONALEESA trials to patients treated in real-world clinical settings.

show abstract

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

Cited by 32 publications

References 5 publications

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

Real-World Outcomes of Treating Advanced Breast Cancer Patients With Palbociclib: A Multicenter Retrospective Cohort Study in Japan—The KBCOG-14 Study

Dose Modifications of Ribociclib and Endocrine Therapy for Treatment of ER+ HER2- metastatic Breast Cancer

Contact Info

Product

Resources

About

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

Cited by 32 publications

References 5 publications

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

Real-World Outcomes of Treating Advanced Breast Cancer Patients With Palbociclib: A Multicenter Retrospective Cohort Study in Japan—The KBCOG-14 Study

Dose Modifications of Ribociclib and Endocrine Therapy for Treatment of ER+ HER2- metastatic&nbsp;Breast Cancer&nbsp;

Contact Info

Product

Resources

About

Dose Modifications of Ribociclib and Endocrine Therapy for Treatment of ER+ HER2- metastatic Breast Cancer