scholarly journals An Indirect Treatment Comparison of the Efficacy of Everolimus (Afinitor®) and Fulvestrant for the Treatment of Hormone Receptor Positive (HR+) HER2 Negative (HER2–) Advanced or Metastatic Breast Cancer

2013 ◽  
Vol 16 (7) ◽  
pp. A393-A394
Author(s):  
D. Chandiwana ◽  
J. Vieira ◽  
J. Granville ◽  
R. McCool ◽  
K. Fleetwood
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Hormone Receptor Positive ◽  
Indirect Treatment

Indirect treatment comparison of the efficacy and safety of olaparib 300 mg tablets BID and talazoparib 1 mg once daily in the treatment of patients with germline BRCA-mutated (gBRCA) HER2-negative metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12570-e12570 ◽  
Author(s):  
Charles McCrea ◽  
Robert Hettle
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Nausea And Vomiting ◽  
Efficacy And Safety ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Increased Risk ◽  
Significant Difference ◽  
Indirect Treatment

e12570 Background: PARP inhibitor treatment with olaparib or talazoparib has been shown to improve progression-free survival (PFS) versus chemotherapy treatment of physician’s choice in patients with germline BRCA-mutated (gBRCA) HER2-negative metastatic breast cancer. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) analysis was performed to simulate the comparative efficacy and safety of alternative PARP treatment in this setting. Methods: Bayesian fixed effects ITCs of data published for OlympiAD (NCT02000622) and EMBRACA (NCT01945775) was conducted using the gemtc package in R. Efficacy analyses were performed on the primary endpoint of PFS by blinded independent central review. Safety analyses included the odds ratio (OR) of adverse event (AE)-related discontinuations, and common AEs of any grade reported in each study. All analyses compared olaparib with talazoparib. Results: Efficacy analyses show no significant difference in PFS across treatments (PFS hazard ratio of 1.09, 95% credible interval [0.72; 1.65]). Safety analyses predict differences in AEs across PARP treatment, including hematological events, alopecia, nausea and vomiting (Table). No difference in AE-related discontinuations was observed (0.93 [0.25–3.42]). Conclusions: Results of the ITC suggest that olaparib and talazoparib are equally efficacious on PFS, and differ in AE risk profile, with olaparib predicted to have fewer common hematological and alopecia events, but an increased risk of nausea and vomiting versus talazoparib. Observed differences require confirmation in comparative studies. Limitations of the analysis include heterogeneity in study design, reporting of AEs, and mix of chemotherapies used in the control arm of the studies. [Table: see text]

Indirect treatment comparison of olaparib and talazoparib in germline BRCA-mutated HER2-negative metastatic breast cancer

2021 ◽  
Author(s):  
Charles McCrea ◽  
Robert Hettle ◽  
Poonam Gulati ◽  
Ankush Taneja ◽  
Preety Rajora
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Fixed Effects ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Significant Difference ◽  
Indirect Treatment

Aim: Two poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib are approved for patients with germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer. Methods: A Bayesian fixed-effects indirect treatment comparison (ITC) analysis was performed to simulate the comparative efficacy (primary outcome of progression-free survival [PFS]) and safety of PARP inhibitor monotherapy. Results: ITC of data from the OlympiAD (olaparib) and EMBRACA (talazoparib) studies suggested no significant difference in efficacy (PFS) between olaparib and talazoparib. However, there were differences in specific adverse events; patients receiving olaparib had a higher rate of nausea and vomiting, while those receiving talazoparib had a higher rate of alopecia and anemia. Discussion: These data support the benefit of the PARP inhibitor class in gBRCAm HER2-negative metastatic breast cancer.

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 Olaparib in hormone receptor-positive, HER2-negative metastatic breast cancer with a somatic BRCA2 mutation

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Lee S. Schwartzberg ◽  
Lesli A. Kiedrowski
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Response ◽  
Hormone Receptor ◽  
Brca2 Mutation ◽  
Locally Advanced ◽  
Susceptibility Gene ◽  
Metastatic Breast ◽  
Breast Cancer Susceptibility Gene ◽  
Hormone Receptor Positive

The oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib is approved for the treatment of patients with human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (mBC) and a germline breast cancer susceptibility gene (BRCA) mutation who have been treated with chemotherapy. This case report describes a 63-year-old postmenopausal woman with somatic BRCA2-mutated mBC who responded to olaparib treatment following multiple prior lines of therapy. The patient presented in January 2012 with locally advanced, hormone receptor-positive (HR+), HER2− BC which, despite initial response to neoadjuvant chemotherapy, recurred as bone disease in February 2014, and subsequently skin (June 2016) and liver (October 2016) metastases. A comprehensive 592-gene next-generation sequencing panel (Caris Life Sciences), performed on a skin biopsy, detected a pathogenic frameshift mutation in BRCA2 (H3154fs, c.9460delC), which was not identified in a 28-gene hereditary cancer germline analysis (Myriad Genetics, Inc.), and was therefore considered to be a somatic mutation. In January 2017, cell-free DNA (cfDNA) analysis (Guardant Health, Inc.) confirmed the BRCA2 H3154fs mutation in plasma. After several lines of chemotherapy and endocrine therapy, deriving clinical benefit from eribulin and capecitabine, the disease progressed by October 2017, and olaparib (300 mg orally twice daily) was initiated in January 2018. By April 2018, the liver lesions had shrunk by 80% and a >90% response in multiple skin lesions was noted. Clinical response was maintained for 8 months, followed by progression in the skin in September 2018. Biopsy of recurrent lesions revealed a novel BRCA2 mutation, E3152del (c.9455_9457delAGG), predicted to restore the open reading frame and presumably the mechanism of resistance to olaparib. Further likely resistance mutations were noted in subsequent cfDNA analyses. This case demonstrated a clinical response with olaparib as a later-line therapy for HR+, HER2− mBC with a somatic BRCA2 mutation.

Phase II Trial of Anastrozole Plus Goserelin in the Treatment of Hormone Receptor–Positive, Metastatic Carcinoma of the Breast in Premenopausal Women

2010 ◽  
Vol 28 (25) ◽  
pp. 3917-3921 ◽  
Author(s):  
Robert. W. Carlson ◽  
Richard Theriault ◽  
Christine M. Schurman ◽  
Edgardo Rivera ◽  
Cathie T. Chung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Phase Ii Trial ◽  
Hot Flashes ◽  
Metastatic Breast ◽  
Premenopausal Women ◽  
Hormone Receptor Positive

Purpose To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor–positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin. Patients and Methods Premenopausal women with estrogen and/or progesterone receptor–positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin. Patients continued on treatment until disease progression or unacceptable toxicity. Results Thirty-five patients were enrolled of which 32 were evaluable for response and toxicity. Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3 months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced stable disease for 6 months or longer for a clinical benefit rate of 71.9%. Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival was not been reached (range, 11.1 to 63+). The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to 5 toxicities. Conclusion The combination of goserelin plus anastrozole has substantial antitumor activity in the treatment of premenopausal women with hormone receptor–positive metastatic breast cancer.

Sign in / Sign up

Export Citation Format

Share Document