Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2– Metastatic Breast Cancer Patients: What Is the Better Choice?

Background: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). Objectives: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. Methods: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. Results: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. Conclusions: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

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Progression free survival and overall survival of CDK 4/6 inhibitors plus endocrine therapy in metastatic breast cancer: a systematic review and meta-analysis

10.21203/rs.2.24219/v1 ◽

2020 ◽

Author(s):

Michela Piezzo ◽

Paolo Chiodini ◽

Maria Riemma ◽

Stefania Cocco ◽

Roberta Caputo ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Metastatic Breast ◽

Progression Free Survival ◽

Visceral Metastases ◽

Metastatic Sites

Abstract PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors to ET is beneficial in terms of PFS irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) and AI-resistant patients (HR 0.77, 95%CI [0.67-0.89]). Pooled data from each single drug show that Palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.

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Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

npj Breast Cancer ◽

10.1038/s41523-021-00281-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Costanza Paoletti ◽

Meredith M. Regan ◽

Samuel M. Niman ◽

Emily M. Dolce ◽

Elizabeth P. Darga ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Metastatic Breast ◽

Progression Free Survival ◽

Cell Number ◽

Rapid Progression ◽

Breast Cancer Patients ◽

Er Positive

AbstractCirculating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.

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Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms21176400 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6400 ◽

Cited By ~ 4

Author(s):

Michela Piezzo ◽

Paolo Chiodini ◽

Maria Riemma ◽

Stefania Cocco ◽

Roberta Caputo ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Meta Analysis ◽

Objective Response ◽

Metastatic Breast ◽

Progression Free Survival ◽

Free Survival ◽

Metastatic Sites

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

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A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2− metastatic breast cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211022890 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110228

Author(s):

Yi Li ◽

Wei Li ◽

Chengcheng Gong ◽

Yabin Zheng ◽

Quchang Ouyang ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Treatment Options ◽

Objective Response ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Progression Free Survival ◽

Subsequent Treatment ◽

Significant Difference

Introduction: Endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) are standard treatment options for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) metastatic breast cancer (MBC). However, the efficacy of standard subsequent therapies after CDK4/6i-based treatment is unclear. This study aimed to examine physician practice patterns and treatment outcomes of subsequent therapies administered after progression on palbociclib therapy in clinical practice. Methods: The study included 200 patients with HR+/HER2– MBC who underwent subsequent treatments after progressing on palbociclib-based regimens in five Chinese institutions between August 2017 and April 2020. The treatment pattern, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were reported. Results: A total of 200 patients were included, of whom 147 (73.5%) and 53 (26.5%) received subsequent chemotherapy and endocrine therapy, respectively. The frequently used monochemotherapy regimens were taxane ( n = 29), capecitabine ( n = 21), and vinorelbine ( n = 17), while the endocrine therapy regimens were chidamide plus exemestane ( n = 16) and everolimus plus exemestane ( n = 9). The overall median PFS (mPFS) was 5.5 months, with no significant difference in mPFS between the chemotherapy and endocrine therapy groups ( p = 0.669). However, among patients not sensitive to prior palbociclib treatment, those administered chemotherapy had significantly longer PFS than those administered endocrine therapy ( p = 0.006). The mPFS with endocrine therapy after first-, second-, and subsequent-line palbociclib was 13.4, 3.1, and 4.1 months, respectively ( p = 0.233); in contrast, the mPFS with chemotherapy was 7.2, 6.5, and 4.9 months after first-, second-, and subsequent-line palbociclib, respectively ( p = 0.364). The median OS was not achieved. The ORR was 10.6% among the 198 patients included in the analysis. Conclusions: Physicians prefer chemotherapy over endocrine therapy for the treatment of patients with HR+/HER2– MBC who develop progression on palbociclib. Sensitivity to previous palbociclib treatment might be one of the indicators for predicting response to subsequent treatment. ClinicalTrials.gov identifier: NCT04517318

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Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920987651 ◽

2021 ◽

Vol 13 ◽

pp. 175883592098765

Author(s):

Raffaella Palumbo ◽

Rosalba Torrisi ◽

Federico Sottotetti ◽

Daniele Presti ◽

Anna Rita Gambaro ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Real World ◽

Hormone Receptor ◽

Metastatic Breast ◽

Progression Free Survival ◽

Her2 Receptor ◽

Treatment Line ◽

Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

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Different survival determinants of metastatic breast cancer patients treated with endocrine therapy or chemo-endocrine therapy.

International Journal of Oncology ◽

10.3892/ijo.12.4.817 ◽

1998 ◽

Author(s):

Y Nomura

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Endocrine Therapy ◽

Metastatic Breast ◽

Breast Cancer Patients

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Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life

Drug Design Development and Therapy ◽

10.2147/dddt.s79563 ◽

2015 ◽

pp. 2189 ◽

Cited By ~ 18

Author(s):

Raffaella Palumbo ◽

Federico Sottotetti ◽

Giuseppe Trifirò ◽

Elena Piazza ◽

Antonella Ferzi ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Breast ◽

Second Line ◽

Prospective Evaluation ◽

Breast Cancer Patients ◽

Line Chemotherapy

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Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218794847 ◽

2018 ◽

Vol 25 (6) ◽

pp. 1374-1380 ◽

Cited By ~ 2

Author(s):

M Alexandra Schickli ◽

Michael J Berger ◽

Maryam Lustberg ◽

Marilly Palettas ◽

Craig A Vargo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Failure ◽

Endocrine Therapy ◽

Metastatic Breast ◽

Second Line ◽

Time To Treatment ◽

Cyclin Dependent Kinases ◽

Hormone Receptor Positive ◽

Time To Treatment Failure

Purpose The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy. Methods This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond. Results Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1–7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9–8.3 months). Conclusions Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.

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Cost Effectiveness Analysis of Eribulin Mesylate as a Treatment for Metastatic Breast Cancer in Spain: Management in the Later Line of Therapy

Journal of Health Economics and Outcomes Research ◽

10.36469/9834 ◽

2015 ◽

Vol 3 (2) ◽

pp. 180-193

Author(s):

Gabriel Tremblay ◽

Unnati Majethia ◽

Ilias Kontoudis ◽

Jesús De Rosendo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cost Effectiveness ◽

Metastatic Breast ◽

Sensitivity Analyses ◽

Line Treatment ◽

Second Line ◽

Life Years ◽

Third Line ◽

Third Line Treatment

Background: Two thirds (62%) of metastatic breast cancer (MBC) patients in Western Europe have human epidermal growth factor receptor 2 (HER2)-negative disease, for which anthracyclines and taxanes are recommended as first-line treatments, followed by microtubule-targeting agents such as capecitabine, vinorelbine and/or eribulin. The study objective was to compare the cost-effectiveness of eribulin in Spain as a second-line treatment for HER2-negative MBC with its current status as a third-line treatment for patients who have received capecitabine. Methods: A Markov model was developed from the perspective of the Spanish healthcare system. The model had three health states: Stable; Progression and Death. In Stable, patients received eribulin or: capecitabine and vinorelbine for HER2-negative patients; primary treatment of physician’s choice (TPC) for post-capecitabine patients. In Progression, all patients received secondary TPC. Model inputs were overall survival, progression-free survival and costs relating to chemotherapies, grade 3/4 adverse events and healthcare utilization. Sensitivity analyses were conducted to identify uncertainty. Results: As second-line treatment, Eribulin was associated with a greater incremental benefit in life years (LYs) and quality-adjusted life years (QALYs) than capecitabine and vinorelbine. Erubilin as third-line treatment was associated with greater benefit in life years (LYs) and QALYs than TPC. The incremental cost-effectiveness ratios (ICERs) for eribulin were higher in the second-line than the third-line setting in terms of LYs (€35,149 versus €24,884) and QALYs (€37,152 versus €35,484). In both settings, deterministic sensitivity analyses demonstrated that the ICER is most sensitive to the eribulin price. Conclusion: Eribulin is cost-effective as second-line treatment for HER2-negative MBC patients in Spain; albeit, slightly less so than as third-line treatment for MBC patients who have received capecitabine (an ICER per QALY difference of €1,668). This difference may fall within the margin of error for the model and could potentially be addressed by a minor reduction in the eribulin price.

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