Phase II trial with letrozole as neoadjuvant treatment in postmenopausal and premenopausal patients with highly endocrine responsive operable breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12125-e12125
Author(s):  
Min-Yi Cheng ◽  
Yi-Fang Zhang ◽  
Ci-Qiu Yang ◽  
Liu-Lu Zhang ◽  
Teng Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Operable Breast Cancer ◽  
Breast Cancers ◽  
Neoadjuvant Endocrine Therapy ◽  
Primary Systemic Therapy ◽  
Premenopausal Patients

e12125 Background: Neoadjuvant endocrine therapy (NET)is effective in postmenopausal patients with breast cancers expressing oestrogen receptor. However, the therapeutic benefit of NET in premenopausal population is not fully characterized. We aimed to assess the efficacy and safety of endocrine therapy between the postmenopausal and premenopausal patients with highly endocrine responsiveoperable breast cancer for primary systemic therapy. Methods: Previously untreated patients with operable breast cancer and highly endocrine responsive breast cancer (ER/PR≥50% and Her2-) were recruited. Patients were assigned to receive letrozole 2.5mg daily (combined with triptorelin in premenopausal patients) for a period of at least 6 months. The primary end point of the study was the objective response rate (ORR) measured by breast ultrasound. Secondary end points included safety, pathologically complete response (pCR) rate, breast conservative surgery (BCS) rate. Results: Between September 2012 and December 2016, 41 patients were enrolled in the study (16 postmenopausal, 25 premenopausal ). The total ORR of this study was 73.2% (30 of 41). No significant differences were seen in the ORR, 76.0% (19 of 25 premenopausal patients) and 68.8% (11 of 16 postmenopausal patients) (P = 0.723). The pCR rate was 8% (2 of 25) for the premenopausal and 0%(0 of 16) for the postmenopausal (p=0.512). The BCS rate was 40% (10 of 25) for the premenopausal and 37.5%(6 of 16) for the postmenopausal (P = 0.873). No treatment-related grade 3/4 adverse events were recorded in both groups. Conclusions: Letrozole shows a high activity and excellent tolerability as neoadjuvant therapy in both postmenopausal and premenopausal patients with highly endocrine responsive operable breast cancer.

Ki67 during and after neoadjuvant trastuzumab, pertuzumab and palbociclib plus or minus fulvestrant in HER2 and ER-positive breast cancer: The NA-PHER2 Michelangelo study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 527-527
Author(s):  
Luca Gianni ◽  
Marco Colleoni ◽  
Giancarlo Bisagni ◽  
Mauro Mansutti ◽  
Claudio Zamagni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptors ◽  
Objective Response ◽  
Complete Response ◽  
Therapeutic Effects ◽  
Unilateral Breast Cancer ◽  
Neoadjuvant Endocrine Therapy ◽  
Er Positive ◽  
Positive Breast Cancer

527 Background: Downregulation of Ki67 by neoadjuvant endocrine therapy predicts activity of endocrine treatments in hormone receptors positive breast cancer. NA-PHER2 is an exploratory phase II study (NCT02530424) assessing Ki67 changes in patients with HER2+ and ER+ breast cancer undergoing dual HER2 block and palbociclib. Cohort A of the NA-PHER2 showed significant decrease of Ki67 at week 2 and at surgery and pathological complete response (pCR) in 27% of patients (Lancet Oncol 2018). Methods: After completing cohort A two additional cohorts were started. In Cohort B cases with HER2 3+ or amplified unilateral breast cancer received therapy with dual block and palbociclib without fulvestrant. In Cohort C tumors with Ki67 >20% and HER2 low (1+/2+, no amplification) received also fulvestrant. Trastuzumab and pertuzumab q3 wks were dosed for 6 cycles and palbociclib for 5 cycles (125 mg po q.d. 3q4 wks). Fulvestrant in Cohort C was given im 500 mg q4 wks for 5 cycles. Primary endpoint was Ki67 change from baseline to 2 weeks and at surgery. Results: 26 eligible patients in cohort B and 23 in cohort C with centrally confirmed HER2 and ER status were recruited. Ki67 was centrally assessed. Main results are reported in the table. Clinical trial information: NCT02530424. The most frequent G >=3 adverse events were neutropenia (36%) and gastrointestinal disorders (12%). Conclusions: Dual block of HER2 and palbociclib caused robust persistent decrease of Ki67 as in cohort A. In cohort B without endocrine therapy there also were pCR and high objective response rate. Effects on Ki67 and ORR were similar in HER2 low tumors. The chemo-free approach of NA-PHER2 leads to promising therapeutic effects and deserves investigation in ER+ HER2+ tumors to spare the toxicity of chemotherapy, and in HER2-low tumors, in which functional activation of HER2 may lead to resistance to endocrine therapy. Supported in part by unrestricted grants of Pfizer Italia S.r.l. and Roche S.p.a. Italia.[Table: see text]

scholarly journals Multidisciplinary Approach to Neoadjuvant Endocrine Therapy in Breast Cancer: A Comprehensive Review

2016 ◽  
Vol 38 (12) ◽  
pp. 615-622 ◽  
Author(s):  
Tomás Reinert ◽  
Susana Ramalho ◽  
Rodrigo Gonçalves ◽  
Carlos Barrios ◽  
Marcia Graudenz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Low Income ◽  
Hormone Receptor ◽  
Urban Areas ◽  
Low Cost ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Breast Cancers ◽  
Neoadjuvant Endocrine Therapy

AbstractBreast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.

scholarly journals Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial

2019 ◽  
Vol 37 (5) ◽  
pp. 386-395 ◽  
Author(s):  
Silvia Dellapasqua ◽  
Kathryn P. Gray ◽  
Elisabetta Munzone ◽  
Daniela Rubino ◽  
Lorenzo Gianni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Locally Advanced ◽  
Premenopausal Women ◽  
Rank Test ◽  
Neoadjuvant Endocrine Therapy ◽  
Endocrine Activity ◽  
Patient Reported ◽  
Premenopausal Patients ◽  
To Receive

PURPOSE To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer. PATIENTS AND METHODS Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2–negative breast cancer were randomly assigned to triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to first assessment of centrally assessed estradiol level ≤ 2.72 pg/mL [≤ 10 pmol/L] during neoadjuvant therapy). The trial had 90% power to detect a difference using a log-rank test with a two-sided α of .05. Secondary end points included response, tolerability, and patient-reported endocrine symptoms. RESULTS Between February 2014 and January 2017, 51 patients were enrolled (n = 26 received triptorelin plus letrozole; n = 25 received degarelix plus letrozole). Time to optimal OFS was three times faster for patients assigned to degarelix and letrozole than to triptorelin and letrozole (median, 3 v 14 days; hazard ratio, 3.05; 95% CI, 1.65 to 5.65; P < .001). Furthermore, OFS was maintained during subsequent cycles for all patients assigned to receive degarelix and letrozole, whereas 15.4% of patients assigned to receive triptorelin and letrozole had suboptimal OFS after cycle 1 (six events during 127 measurements). Adverse events as a result of both degarelix plus letrozole and triptorelin plus letrozole were as expected. CONCLUSION In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with triptorelin.

Oral vinorelbine (NVBo) and anastrozole (A) as neoadjuvant treatment of locally advanced (LA) breast cancer (BC) in hormone receptor positive (HR+) postmenopausal patients: Results of an international phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 600-600
Author(s):  
M. Riggi ◽  
E. M. Moreno-Lopez ◽  
J. Rolski ◽  
P. Petruzelka ◽  
J. M. Ferrero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Conservative Surgery ◽  
Ultra Sound ◽  
Oral Vinorelbine ◽  
Hormone Receptor Positive

600 Background: Two recent randomized studies with anastrozole, as single agent or with an unspecified cytotoxic, produced an objective response rate (RR) of 24 and 39.5% by ultra-sound (US) [baseline primary tumor diameters (PTD) of 2.6 cm (median) and 3.6 cm (mean), respectively] in LA BC. This trial assessed the effect of the combined NVBo-A therapy. Methods: 55 assessable HR+ patients (pts) with LA breast cancer (tumor size > 3 cm) were expected, including 10 with pharmacokinetics (PK). Pts received 3 (if progression or complete response) to 6 courses of NVBo at day 1(D1) and 8 every 3 weeks (60 mg/m2 escalated to 80 mg/ m2 at cycle 2) with 1 mg of A daily. Both US (primary criteria) and calliper assessments were performed at cycle 3 and 6, with surgery within 4 weeks of the last D1 NVBo. Anastrozole interaction on NVBo was studied by comparing NVBo PK between D1 and D8. NVBo interaction on A was assessed by comparing trough concentrations between D8 and D21. Results: Between July 2005 and June 2008, 60 women were enrolled. The first 58 pts were analyzed: at baseline, median age 64.9 years, median and mean PTD 3.7 and 4 cm, respectively; 59% N1–2(17% N2), with a feasible breast conservative surgery (BCS) in only 12%; 19% were inoperable. The RR was 59% (95% CI 45–71%) by US and 69% (55–80%) by calliper. Clinical nodal invasion on TNM (N+) regressed by 32%. 10/11 inoperable pts at baseline became operable. Among 51 resections (concurrent events 4 pts, unresectable 3 pts) 20% were BCS. The pCR was 3.9%. Grade (G) 3–4 toxicities: haematological toxicities (neutropenia) in 6 pts; hepatic enzymes G3 1 pt; gastrointestinal toxicities G3 5 pts and 1 G4 musculoskeletal pain. PK interim analysis showed an absence of interaction between the 2 drugs. Conclusions: NBVo plus A led to an increased RR compared with previous experiences with A alone or not (IMPACT, PROACT trials). The operability rate was notably improved from baseline in this population with unfavorable characteristics and BCS was slightly increased. This combination treatment was well tolerated and pts could benefit from an oral therapy allowing preservation of daily living activities. [Table: see text]

Pathologic Complete Response With Six Compared With Three Cycles of Neoadjuvant Epirubicin Plus Docetaxel and Granulocyte Colony-Stimulating Factor in Operable Breast Cancer: Results of ABCSG-14

2007 ◽  
Vol 25 (15) ◽  
pp. 2012-2018 ◽  
Author(s):  
Günther G. Steger ◽  
Arik Galid ◽  
Michael Gnant ◽  
Brigitte Mlineritsch ◽  
Alois Lang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Operable Breast Cancer ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Purpose Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate. Patients and Methods Patients with biopsy-proven breast cancer (T1-4a-c, N±, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery. Results A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment. Conclusion Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.

Randomized, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal b/HER2 normal breast cancer (GENEVIEVE).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS1138-TPS1138
Author(s):  
Stefan Paepke ◽  
Sherko Kümmel ◽  
Jens U. Blohmer ◽  
Serban Dan Costa ◽  
Holger Eidtmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Objective Response ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Breast Conservation ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Open Label ◽  
Luminal B

TPS1138 Background: Cabazitaxel is a new taxoid promoting the tubulin assembly in vitro and stabilizing microtubules against cold-induced depolymerization as efficiently as docetaxel. It has shown superior survival against mitoxantrone plus prednisone in docetaxel pre-treated hormone refractory metastatic prostate cancer pts leading to its registration. It showed a favorable toxicity profile with a low rate of alopecia. In the GENEVIEVE study it will be compared to weekly paclitaxel, which is currently most widely used in breast cancer (BC) pts. Methods: This is a prospective multicenter, randomized, open label study investigating efficacy and safety of cabazitaxel. Pts with uni- or bilateral primary BC (stage cT3/T2/T1c and cN+/T1c and pNSLN+), tumor lesion ≥ 2cm (palpation) or ≥ 1cm (sonography) and centrally confirmed TNBC or luminal B/HER2- can be included. Pts will be randomized to four q3w cabazitaxel (25mg/m² i.v.) vs. 12 q1w paclitaxel (80mg/m² i.v.). Randomization will be stratified by nodal status and subtype. Treatment will be given until surgery, disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is pathologic complete response (pCR) (ypT0/is ypN0/+). Secondary objectives are pCR in stratified subgroups and by other definitions, objective response rate, pCR and local recurrence free survival in pts with clinical complete response and neg. core biopsy before surgery, breast conservation rate, toxicity, compliance, survival rates, biomarkers predicting response. Assuming 15% pCR in controls and targeting a smallest clinical improvement of 10% (i.e. pCR = 25% in experimental arm), a total of 326 pts (163/arm) are required for the one-sided proportion comparison test (α=0.1) with 80% power. The trial is registered under NCT01779479. Results: Recruitment is planned for 12 mths in 45 (+10 back-up) sites in Germany. 1st pt in is planned for Feb 2013. Conclusion: GENEVIEVE will rapidly and precisely compare efficacy and tolerability of cabacitaxel vs. paclitaxel to decide if further development in BC is reasonable. Clinical trial information: NCT01779479.

Neoadjuvant Treatment of Postmenopausal Breast Cancer With Anastrozole, Tamoxifen, or Both in Combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) Multicenter Double-Blind Randomized Trial

2005 ◽  
Vol 23 (22) ◽  
pp. 5108-5116 ◽  
Author(s):  
Ian E. Smith ◽  
Mitch Dowsett ◽  
Stephen R. Ebbs ◽  
J. Michael Dixon ◽  
Anthony Skene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Postmenopausal Women ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Her2 Positive ◽  
Long Term Outcome ◽  
Er Positive

Purpose The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) –positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial. Patients and Methods Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2) –positive cancers, and tolerability. Results There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated. Conclusion Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.

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