scholarly journals Clinicopathological Features Related to the Efficacy of CDK4/6 Inhibitor-Based Treatments in Metastatic Breast Cancer

2022 ◽  
Vol 16 ◽  
pp. 117822342110651
Author(s):  
Ayana Shikanai ◽  
Yoshiya Horimoto ◽  
Yumiko Ishizuka ◽  
Toshitaka Uomori ◽  
Katsuya Nakai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptors ◽  
Financial Burden ◽  
Primary Tumour ◽  
Metastatic Breast ◽  
Clinicopathological Features ◽  
Tumour Grade ◽  
Metastatic Lesions

Background: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial. Methods: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied. Results: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade ( P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline ( P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions. Conclusion: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.

scholarly journals 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

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.

scholarly journals Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Thomas Grinda ◽  
Natacha Joyon ◽  
Amélie Lusque ◽  
Sarah Lefèvre ◽  
Laurent Arnould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Large Scale ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Multivariable Analysis ◽  
Real Life ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Risk Of Death

AbstractExpression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

scholarly journals Dutch Breast Cancer Trialists' Group (BOOG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 61-79
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Phase Iii ◽  
List Type ◽  
First Line ◽  
Open Label ◽  
Phase Iii Study

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Dutch breast cancer trialists' group (BOOG). Clinical trials include:An open label randomized (inter)national multicenter comparative trial of 5 years adjuvant endocrine therapy with an LHRH agonist plus an aromatase inhibitor (goserelin + anastrozole) versus five courses FE90C chemotherapy followed by the same endocrine therapy in pre- or perimenopausal patients with hormone receptor-positive primary breast cancer (PRemenopausal Optimal Management IS Endocrine therapy). BOOG 2002-01/PROMISE. ISRCTN23561723Open label, comparative, randomized, multicenter, study of trastuzumab (Herceptin) given with docetaxel (Taxotere) versus sequential single agent therapy with trastuzumab followed by docetaxel as first-line treatment for metastatic breast cancer (MBC) patients with HER2neu overexpression. BOOG 2002-02/HERTAX ISRCTN13770586Micro-metastases and Isolated tumour cells: Robust and Relevant Or Rubbish? The MIRROR study in BREAST CANCER. BOOG 2003-03/ZonMW 3214Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed. BOOG 2004-01/Young Boost SRCTN45066831Microarray analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens, a randomized phase III study. MATADOR, BOOG 2005-02, CKTO 2004-04 ISRCTN61893718A prospective randomised, open, multicentre, phase III study to assess different Durations of Anastrozole therapy after 2–3 years Tamoxifen as Adjuvant therapy in postmenopausal women with breast cancer. 2006-01/DATAA randomized, open-label phase III study of first line chemotherapy in elderly metastatic breast cancer patients, comparing intravenous pegylated liposomal doxorubicin with oral capecitabine; and the incorporation of a complete geriatric assessment. 2006-02/OMEGABOOG participation in International studies:. BOOG 2001-01/TEAM trial. BOOG 2001-02/AMAROS (EORTC 10981/22023). BOOG 2002-04/HERA (BIG 1-01/EORTC 10011/BO16348B). BOOG 2003-02 (BIG 1-02/IBCSG 27-02). BOOG 2003-04 (GBG 29). BOOG 2004-02/TBP (GBG 26, BIG 3-05). BOOG 2005-01/CASA (IBCSG 32-05/BIG 1-05). BOOG 2005-03/MINDACT (EORTC 10041, BIG 3-04). BOOG 2006-03/SUPREMO (BIG 2-04). BOOG 2006-04/Adjuvant lapatinib study (BIG 2-06/EGF106708)

Real-world Indian scenario of CDK4/6 inhibitors (palbociclib and ribociclib) with endocrine therapy in upfront hormone positive metastatic breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13028-e13028
Author(s):  
Ajay Gogia ◽  
Shalabh Arora ◽  
Priyanshu Choudhary ◽  
Rakesh Kumar ◽  
Sanjay Thulkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
De Novo ◽  
Metastatic Breast ◽  
Common Side Effect ◽  
Drug Discontinuation ◽  
Grade 3 ◽  
Visceral Disease

e13028 Background: CDK4/6 inhibitors (CDKi), in combination with endocrine therapy (ET), has become the standard of care in the treatment of hormone positive (HR+)/ HER2 neu negative metastatic breast cancer (MBC) patients. We evaluated clinical outcomes and toxicity in MBC patients, who have received ET with two CDKi, namely palbociclib and ribociclib. Methods: This is an ambispective, single institutional analysis of de-novo HR+ MBC patients treated with CDKi (palbociclib 125 mg and ribociclib 600 mg once a day for 21 days /28 days cycle) from November 2016- October 2020 at AIIMS, New Delhi, India. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was response rate and toxicity. A total of 157 female patients were recruited in this study however the response and toxicity data were available in 120 cases. All premenopausal women received ovarian suppression or ovarian ablation. Results: A total of 120 patients were included in this study with a median age of 57 years (35-75) and 93 (77.5%) cases were postmenopausal. Twenty-three (19.1%) patients had a bone-only disease, 49 (40.9%) had bone and visceral disease and 48 (40%) had only visceral disease. In this study 91 (75.9%) patients received palbociclib and 29 (24.2%) received ribociclib. The median PFS was 18 months (4-36). Twenty four (20%) patients achieved a complete response, 69 (57.5%) patients attained partial response, 18(15%) patients had stable disease and 9 (7.5%) had disease progression. Grade 3–4 neutropenia, thrombocytopenia, and anaemia were observed in 18(15%), 8 (6.7%), and 4 (3.3%) cases respectively. None of the patients developed febrile neutropenia. Cutaneous, renal, hepatic, and gastrointestinal toxicity was observed in 1,1,3,4 cases respectively. Prolonged QTc was observed in one case. Grade 3 fatigue was observed in 7 cases. Dose interruption/delay (mean dose delay of 7 days), dose modification, and drug discontinuation were observed in 24 (20%), 12 (10%), and 10 (8.3%) of cases respectively. Conclusions: This is one of the largest real-world Indian data on CDK4/6 inhibitors on upfront HR+ MBC. Side effects are less than published literature with similar efficacy. Neutropenia was the most common side effect which was managed by brief dose interruption.

scholarly journals Metastatic breast cancer in males assessment of endocrine therapy

Cancer ◽  
1984 ◽  
Vol 53 (6) ◽  
pp. 1344-1346 ◽  
Author(s):  
Jashbhai K. Patel ◽  
Takuma Nemoto ◽  
Thomas L. Dao
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast

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

2018 ◽  
Vol 25 (6) ◽  
pp. 1374-1380 ◽  
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.

scholarly journals Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Duman BB ◽  
Cil T
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Hormone Receptor ◽  
Tumor Heterogeneity ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Her2 Overexpression

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.

Endocrine therapy-based strategies with different endocrine sensitivity statuses for hormone receptor positive/HER2 negative metastatic breast cancer: A network meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1062-1062
Author(s):  
Jiani Wang ◽  
Yiqun Han ◽  
Jiayu Wang ◽  
Binghe Xu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Therapy Resistance ◽  
Optimal Treatment ◽  
Hormone Receptor Positive ◽  
Direct Head

1062 Background: Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Since the absence of direct head-to-head comparisons for all regimens, decision-making guidelines are urgently needed for different endocrine sensitivity statuses. This study is to evaluate the efficacy of ET-based regimens in patients with HR+/HER2- MBC and to assess the heterogeneity among different compounds with a particular focus on their ability to improve survival outcomes. Methods: This network meta-analysis of phase II/III randomized controlled trials (RCTs) with at least one ET in HR+/HER2- MBC were enrolled. Based on the endocrine responses, participants were stratified into endocrine therapy sensitivity (ETS) and endocrine therapy resistance (ETR) groups. Primary endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed by bayesian algorithms and primarily measured as surface under the cumulative ranking curve (SUCRA). Results: A total of 42 trials (22917 patients) were included. Regarding PFS, cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) +fulvestrant 500mg (F500) was recommended for the ETS group (SUCRA = 76.92%), while chemotherapy was considered as the most effective option for the ETR group (SUCRA = 73.47%). For visceral metastases, CDK4/6i +aromatase inhibitors (AIs) could provide the extreme efficacy for the ETS group (SUCRA = 63.27%) while the CDK4/6i +F500 (SUCRA = 76.17%) as the prior regimen for the ETR group. For bone-only disease, CDK4/6i+F500 was preferred for both the ETS (SUCRA = 67.04%) and the ETR (SUCRA = 70.24%) group. Concerning OS, CDK4/6i+tamoxifen was estimated as the first-rank regimen for the ETS subgroup (SUCRA = 67.04%) and chemotherapy for the ETR subgroup (SUCRA = 60.02%). Regarding resistance category, abemaciclib +F500 was likely the best option with PFS, for both primary (SUCRA = 69.19%) and secondary ETR (SUCRA = 69.09%) settings, as well as primary ETR associated with OS improvement (SUCRA = 67.67%). Pictilisib +F500 could be the optimal treatment with OS for secondary ETR (SUCRA = 60.50%)group. Conclusions: The results showed that CDK4/6i + F500 was probably the most promising option in ETS, visceral ETR and bone-only disease settings in terms of PFS. OS subgroup analysis showed that different endocrine sensitivity statuses required various optimal treatment strategies.

Sign in / Sign up

Export Citation Format

Share Document