scholarly journals A phase II trial of cabozantinib in hormone receptor-positive breast cancer with bone metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1062-1062
Author(s):  
Jing Xu ◽  
Michaela Jane Higgins ◽  
Sara M. Tolaney ◽  
Steven E. Come ◽  
Matthew Raymond Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Control ◽  
Bone Metastases ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Hormone Receptor ◽  
Bone Scan ◽  
Response Rate ◽  
Hormone Receptor Positive ◽  
Initial Starting

1062 Background: We assessed the antitumor activity of cabozantinib, a potent multi-receptor oral tyrosine kinase inhibitor with activity against MET, RET, VEGFR2, and AXL, in patients with hormone-receptor positive (HR+) breast cancer with bone metastases. Methods: In this single-arm multicenter phase II study, patients with HR+, HER2- metastatic breast cancer and ≥ 1 prior line of therapy received an initial starting dose of 100 mg cabozantinib, later reduced to 60 mg per day. The primary endpoint was bone scan response rate determined by independent central review and defined as percent change of bone scan area from baseline. The target bone scan response rate was 30% compared to a null response rate of 10%. Secondary endpoints included objective response rate (ORR) by RECIST v1.1, progression free (PFS) and overall survival (OS). Bone scan and CT were obtained every 12 weeks. Results: Among 52 enrolled patients, median age was 55, and 54% and 42% had > 2 lines prior endocrine and chemotherapy, respectively and 18 (35%) had bone-only disease. 20 (38%) experienced a partial bone scan response and 6 (12%) had stable disease (SD). 16 (31%) patients discontinued study prior to week 12 assessment for early clinical progression or toxicity, and three (6%) had missing follow-up scans. Best extra-osseous overall response revealed SD in 26 (50%), but no objective responses. In 25 patients with bone scan disease control at 12 weeks, only 3 (12%) developed extra-osseous progression. Median PFS was 4.3 months (90% CI 2.8 - 5.5) and OS was 19.6 months (90% CI 18.0 – 26.8). In a landmark analysis, patients with bone scan disease control at 12 weeks had longer OS (median 24.2 months, 90% CI 16.4 – 31.7) than those without (median OS 13.3 months, 90% CI 9.5 – 18.2), with a hazard ratio of 0.37 (90% CI 0.21 – 0.65). Most common grade 3 or 4 toxicities were hypertension (10%), anorexia (6%), diarrhea (6%), fatigue (4%) and hypophosphatemia (4%). Dose reduction or delay occurred in 42 (81%) patients. Conclusions: This study met its primary endpoint with bone scans improved in 38% of patients with metastatic HR+ breast cancer and remained stable in an additional 12% with cabozantinib treatment. Bone scan response correlated with improved OS. This is the first reported study in breast cancer to use bone scan response as a primary endpoint. Further studies with cabozantinib in HR+ breast cancer and additional validation of bone scan response as a surrogate for clinical benefit in breast cancer are warranted. Clinical trial information: NCT01441947 .

A phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS652-TPS652
Author(s):  
Ahmad Awada ◽  
Javier Cortes ◽  
Miguel Martin ◽  
Philippe Aftimos ◽  
Mafalda Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Hormone Receptor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

TPS652 Background: Hormone receptor-positive, HER2-negative breast cancer (BC) is currently associated with 3-4 years overall survival in the metastatic setting and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T is a cytotoxic agent that forms a complex with the XPG, inducing cell apoptosis. As a single agent, T has shown anti-tumor activity in patients with poor prognosis BC, and a better response to T in BC patients with XPG RNA overexpression has been observed. Methods: This is an open-label, phase II study of T (1.3 mg/m2 in 3-hour intravenous infusion every 3 weeks) in patients with hormone receptor-positive, HER2-negative advanced BC, according to their primary tumor’s XPG expression. Primary endpoint: to evaluate the efficacy of T in terms of progression free survival rate at 4 months (PFS4) according to the patient’s XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety profile in XPG-high and XPG-low patients. Assignment: BC patients who have previously received anthracyclins and/or taxanes and who progressed after 2-5 chemotherapy lines will be assigned according to their XPG expression from paraffin embedded tumor samples to stratum A (XPG-high [>3]) or to stratum B (XPG-low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial). Statistical methods: A two-stage design was chosen: at a first stage 20 patients will be enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint (PFS4) will be conducted once 40 evaluable patients have been recruited. If ≥ 7 out of 20 patients achieve PFS4, recruitment will continue to a maximum sample size of 50 evaluable patients per stratum. If ≥ 22 out of 50 patients achieve PFS4, T will be considered active in this group (alpha error: 0.025, power: 80%). To date, 35 patients (16 XPG-high and 15 XPG-low) have been enrolled from three countries and five centers. Recruitment is ongoing.

scholarly journals A Phase II Trial of Cabozantinib in Hormone Receptor‐Positive Breast Cancer with Bone Metastases

2020 ◽  
Vol 25 (8) ◽  
pp. 652-660 ◽  
Author(s):  
Jing Xu ◽  
Michaela J. Higgins ◽  
Sara M. Tolaney ◽  
Steven E. Come ◽  
Matthew R. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Phase Ii Trial ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

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.

scholarly journals Correction: A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor–positive Breast Cancer

2021 ◽  
Vol 27 (5) ◽  
pp. 1582-1582
Author(s):  
Sara M. Tolaney ◽  
Solmaz Sahebjam ◽  
Emilie Le Rhun ◽  
Thomas Bachelot ◽  
Peter Kabos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Phase Ii Study ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Everolimus and exemestane in hormone receptor-positive advanced breast cancer: A comprehensive cancer center’s experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13017-e13017
Author(s):  
Inês Moreira ◽  
Marta Ferreira ◽  
Ana Afonso ◽  
Ana Ferreira ◽  
Ana Rodrigues ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Advanced Breast ◽  
Overall Response ◽  
Hormone Receptor Positive

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer

2020 ◽  
Vol 20 (3) ◽  
pp. 238-245 ◽  
Author(s):  
Romualdo Barroso-Sousa ◽  
Ian E. Krop ◽  
Lorenzo Trippa ◽  
Zhenying Tan-Wasielewski ◽  
Tianyu Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Palliative Radiotherapy ◽  
Hormone Receptor Positive
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