scholarly journals Target therapy of luminal HER2-negative advanced breast cancer with PIK3CA mutation: combination of alpelisib plus fulvestrant in real clinical practice

2021 ◽  
pp. 75-82
Author(s):  
D. A. Filonenko ◽  
T. M. Ibragimova ◽  
N. I. Polshina ◽  
A. V. Belogurova ◽  
E. I. Khatkova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Advanced Breast Cancer ◽  
Disease Progression ◽  
Pik3ca Mutation ◽  
Advanced Breast ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Real Clinical Practice

Introduction. Сombination of alpelisib plus fulvestrant is approved in patients with hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer (ABC) after progression on hormonotherapy. Efficacy data of alpelisib in heavily pretreated patients with HR+/HER-2-, PIK3CA-mutated advanced breast cancer are limited, only results from phase I trial are available. Here we report our results of alpelisib efficacy in 19 heavily pretreated patients.Object: to evaluate efficacy and safety of combination alpelisib plus fulvestrant in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer in initial and later lines of therapy in real clinical practice.Materials and methods. Combination of  alpelisib plus fulvestrant was investigated in  19  patients with HR+/HER2-, PIK3CAmutated ABC, alpelisib at a dose of 300 mg per day plus fulvestrant at a dose of 500 mg i.m. every 28 days and once on day 15. Treatment continued until disease progression or unacceptable toxicity.Results. From February 2021 19 patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer were treated with alpelisib plus fulvestrant. The data cut off is October 2021. Median lines of treatment in advanced disease was five, including 19 (100%) patients received CDK4/6, 14 (74%) – fulvestrant and/or everolimus and 15 (79%) – chemotherapy. 4 (21%) received alpelisib in a second line, 15 (79%) – in subsequent lines. Median progression-free survival was 7 months. The response was evaluated in 18 patients: partial response was achieved in 5 (28%) patients, stable disease – in 9 (50%), disease progression – 4 (22%). The most frequent adverse events were hyperglycemia – 74% (grade 3 – 22%), creatinine increased – 42% and rash – 37% (grade 3 – 22%). Only one patient has discontinued the treatment due to Quincke`s edema.Conclusions. Combination of alpelisib with fulvestrant is an effective option both in initial and later lines of therapy in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer including fulvestrant, CDK4/6 inhibitors and/or everolimus – pretreated patients. 

Phase II study of mitomycin-C and cisplatin in heavily pretreated advanced breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10713-10713
Author(s):  
X. Hu ◽  
H. Guo ◽  
X. Yang ◽  
X. Zhao ◽  
Y. Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Mitomycin C ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Advanced Breast ◽  
Standard Chemotherapy Regimen ◽  
Heavily Pretreated ◽  
Progression Of Disease ◽  
Grade 3

10713 Background: There were no standard chemotherapy regimen to patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. The mitomycin-C and cisplatin combination was investigated in this subgroup of patients. Methods: Three-weekly regimen consisted of mitomycin, 6 mg/m2 administered intravenously on day 1, and cisplatin, 25 mg/m2 intravenously on day 1–3. Results: 38 patients aged 25–75 years (median: 46 years) were treated with an overall response rate of 31.6%. The median time to progression (TTP) was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, p = 0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 (10.5%), 4 (10.5%) and 3 (7.9%) patients, respectively. The median overall survival was 13+ months. Conclusions: The mitomycin-C/cisplatin doublet showed antitumor activity for anthracycline-, vinorelbine-, and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China. No significant financial relationships to disclose.

Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer.

1995 ◽  
Vol 13 (2) ◽  
pp. 314-322 ◽  
Author(s):  
B Chevallier ◽  
P Fumoleau ◽  
P Kerbrat ◽  
V Dieras ◽  
H Roche ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Performance Status ◽  
Advanced Breast ◽  
First Line ◽  
European Organization ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Line Chemotherapy

PURPOSE This trial investigated the toxicity and efficacy of docetaxel as first-line chemotherapy in women with heavily pretreated advanced breast cancer. PATIENTS AND METHODS From April 1992 to August 1992, 35 patients with advanced breast cancer from 29 to 65 years of age with a performance status of 0 to 2 were entered onto the study. Docetaxel 100 mg/m2 was administered every 3 weeks as a 1-hour infusion on day 1 without routine premedication for hypersensitivity reactions. Thirty-one patients were assessable for response. Previous adjuvant chemotherapy had been given to 11 patients. RESULTS Five complete responses (CRs) and 16 partial responses (PRs) were observed, for an overall response rate of 67.7% (95% confidence interval, 49% to 83%). A CR occurred at 13 of 45 assessable sites (four liver, two lung, three breast, three lymph node, and one skin). The median duration of response was 44+ weeks, the median time to disease progression 37+ weeks, and the median overall survival time 16+ months. Among 34 patients assessable for toxicity (177 cycles; median, five cycles per patient), the following side effects were reported: nadir neutropenia grade 3 (three patients); grade 4 (31 patients); no grade 3 to 4 infection, acute hypersensitivity-like reaction (10 patients); grade 2 to 3 alopecia (all patients); and grade 2 to 3 nausea and vomiting (six patients). Fluid retention occurred in 26 patients and consisted of weight gain, edema alone (15 patients), or edema associated with serous effusion (11 patients). This side effect led to treatment discontinuation in 16 of 21 responding patients after a median of five cycles and a median cumulative dose of docetaxel of 574 mg/m2. CONCLUSION Our data suggest that docetaxel has major antitumor activity when used as a single cytotoxic agent as first-line chemotherapy in advanced breast cancer.

Safety and efficacy of eribulin in patients with advanced breast cancer treated outside of a clinical trial: A single institution experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11510-e11510
Author(s):  
Luisa Kessler ◽  
Jonas Bergh ◽  
Theodoros Foukakis
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Advanced Breast Cancer ◽  
Objective Response ◽  
Advanced Breast ◽  
Internal Quality ◽  
Safety And Efficacy ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Time Point

e11510 Background: Eribulin is a non-taxane, microtubule dynamics inhibitor that was approved for the treatment of patients with metastatic breast cancer (MBC) in Europe in March 2011. Experience with routine use of eribulin is limited. Methods: All patients receiving eribulin at the Oncology Department, Karolinska University Hospital outside of a clinical trial are treated according to the approved indication and dosology. For the purpose of an internal quality control, treated patients are registered in a database. All patients registered at the time point of the analysis were evaluated for safety and efficacy. Treatment toxicity including fatigue, neurotoxicity and infection was graded according to CTCAE v4.0. Efficacy was investigated using the routinely performed radiological assessments. Results: To date, twenty patients have received a total of 104 cycles of eribulin. All patients were heavily pretreated with a median of 3 (range 1-6) previous chemotherapy lines for MBC. The median age of the patients was 54 years (range 35-74). Fourteen patients are alive and 12 are still undergoing treatment with eribulin. No hypersensitivity reactions and no toxic deaths were seen. Fatigue was observed in 45% of the patients (grade 3 20%), while 20% experienced neurotoxicity and 35% were treated for an infection (grade 3 20%). None of the patients experienced grade 3 neurotoxicity. Interestingly, 3 cases of Herpes zoster reactivation were observed. Fifteen of the patients have been radiologically assessed at the time point of the analysis. Six of those patients had partial response (PR), one patient had complete response (CR) and one patient had stable disease (SD). Seven patients had progressive disease (PD). Conclusions: Eribulin administered outside of a clinical trial in patients with advanced breast cancer was safe and well tolerated. Although the majority of the patients were heavily pretreated, objective response was seen in nearly half of the cases.

scholarly journals The place of CDK4/6 inhibitors in real clinical practice for patients with hormone-positive HER2-negative advanced breast cancer: opinion of Moscow’s oncologists

2020 ◽  
Vol 16 (1) ◽  
pp. 32-36
Author(s):  
L. G. Zhukova ◽  
M. A. Mukhina
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Advanced Breast Cancer ◽  
Randomized Clinical Trials ◽  
Survival Rates ◽  
Advanced Breast ◽  
Baltic Region ◽  
Biological Features ◽  
Significant Efficacy ◽  
Real Clinical Practice

The use of CDK4/6 inhibitors in combination with endocrine therapy (aromatase inhibitors and fulvestrant) allowed us to radically change our understanding of opportunities in the treatment of hormone-positive HER2-negative advanced breast cancer and determine optimal therapy sequencing. The results of randomized clinical trials and over 5-years accumulated international experience in the use of CDK4/6 inhibitors in real clinical practice prove that the use of combinations with CDK4/6 inhibitors can achieve significant efficacy results and increase the survival rates when prescribed in 1 and 2 lines of treatment.In this paper, we present the results of a survey conducted in July–October 2019 among 48 oncologists in Moscow, that were asked to choose, in their opinion, the most preferable patient’s profile and molecular and biological features of hormone-positive HER2-negative advanced breast cancer, in which the use of combination therapy with CDK4/6 inhibitors will provide the greatest benefit.Conflict of interest. MD M.A. Mukhina is the medical director of oncology in the Eurasia and Baltic region of Pfizer Innovations Company

Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

2005 ◽  
Vol 23 (23) ◽  
pp. 5314-5322 ◽  
Author(s):  
Stephen Chan ◽  
Max E. Scheulen ◽  
Stephen Johnston ◽  
Klaus Mross ◽  
Fatima Cardoso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Dose Level ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: Baseline characteristics and safety evaluation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1012-1012
Author(s):  
Philippe Caillet ◽  
Marina Pulido ◽  
Etienne Brain ◽  
Claire Falandry ◽  
Isabelle Desmoulins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Real World ◽  
Older Patients ◽  
Systemic Treatment ◽  
Safety Data ◽  
Real Life ◽  
Advanced Breast ◽  
Baseline Characteristics ◽  
Grade 3

1012 Background: Advanced breast cancer (ABC) is common in older patients, resulting from the high incidence of breast cancer beyond age 70. This population is often limited in clinical trials. Endocrine therapy (ET) combined with a CDK4/6 inhibitor is the standard of care in ABC overexpressing hormonal receptors (HR+). Data specific to older patients are scarce in the literature, deserving further research. Methods: PALOMAGE is an ongoing French prospective study evaluating palbociclib (PAL) + ET in real life setting in women aged ≥70 with HR+ HER2- ABC, split in 2 cohorts: ET sensitive patients with no prior systemic treatment for ABC (cohort A), and ET resistant patients and/or with prior systemic treatment for ABC (cohort B). Data collected include clinical characteristics, quality of life (EORTC QLQ-C30 and ELD14) and geriatric description [G8 and Geriatric-COre DatasEt (G-CODE)]. This analysis reports on baseline characteristics and safety data for the whole population. Results: From 10/2018 to 10/2020, 400 and 407 patients were included in cohort A and B, respectively. The median age was 79 years (69-98), 15.1% with an age > 85. ECOG performance status (PS) was ≥2 in 17.9% patients, 68.3% had a G8 score ≤14 suggesting frailty, 32.1% had bone only metastasis, and 44% had visceral disease. 35.8% of patients in cohort B had no prior treatment for ABC. Safety data were available for 787 patients. The median follow-up was 6.7 months (IC95% = 6.1-7.6). At start of treatment, full dose of PAL (125 mg) was used in 76% of the patients: 62.6%, 68.7% and 71.6% of patients aged ≥ 80, those with ECOG PS ≥2 and those with a G8 score ≤14, respectively. In the safety population, 70% had ≥1 adverse event (AE), including 43.1% grade 3/4 AE, and 22.9% ≥ 1 serious AE. Most frequent AE reported were neutropenia (43.2%), anemia (17.5%), asthenia (16.3%) and thrombocytopenia (13.6%). Grade 3/4 neutropenia was observed in 32.3% of patients, with febrile neutropenia in 1.1%. Grade 3/4 AE PAL-related were reported in 40.1%, 31.4% of patients aged < 80, ≥80, respectively. Regarding PAL, 23.4% of patients had a dose reduction and 41.8% had a temporary or permanent discontinuation due to AE. Safety data were similar in both cohorts. Geriatric data and impact on safety will be presented. Conclusions: PALOMAGE is a unique large real-world cohort focusing on older patients treated with PAL in France. These preliminary data do not suggest any new safety signal, matching data derived from PALOMA trials. The occurrence of less grade3/4 AE related to PAL in patients aged 80 and beyond might reflect the 30% decrease of PAL dose upfront. Effectiveness analyses are eagerly awaited. Clinical trial information: EUPAS23012 .

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