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

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

2021 ◽  
pp. 75-82
Author(s):  
D. A. Filonenko ◽  
T. M. Ibragimova ◽  
N. I. Polshina ◽  
A. V. Belogurova ◽  
E. I. Khatkova ◽  
...  

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. 


2018 ◽  
Vol 78 (05) ◽  
pp. 469-480
Author(s):  
Michael Untch ◽  
Rachel Würstlein ◽  
Norbert Marschner ◽  
Diana Lüftner ◽  
Doris Augustin ◽  
...  

AbstractThe fourth international advanced breast cancer consensus conference (ABC4) on the diagnosis and treatment of advanced breast cancer (ABC) headed by Professor Fatima Cardoso was once again held in Lisbon on November 2 – 4, 2017. To simplify matters, the abbreviation ABC will be used hereinafter in the text. In clinical practice, the abbreviation corresponds to metastatic breast cancer or locally far-advanced disease. This year the focus was on new developments in the treatment of ABC. Topics discussed included the importance of CDK4/6 inhibition in hormone receptor (HR)-positive ABC, the use of dual antibody blockade to treat HER2-positive ABC, PARP inhibition in triple-negative ABC and the potential therapeutic outcomes. Another major area discussed at the conference was BRCA-associated breast cancer, the treatment of cerebral metastasis, and individualized treatment decisions based on molecular testing (so-called precision medicine). As in previous years, close cooperation with representatives from patient organizations from around the world is an important aspect of the ABC conference. This cooperation was reinforced and expanded at the ABC4 conference. A global alliance was founded at the conclusion of the consensus conference, which aims to promote and coordinate the measures considered necessary by patient advocates worldwide. Because the panel of experts was composed of specialists from all over the world, it was inevitable that the ABC consensus also reflected country-specific features. As in previous years, a team of German breast cancer specialists who closely followed the consensus voting of the ABC panelists in Lisbon and intensively discussed the votes has therefore commented on the consensus in the context of the current German guidelines on the diagnosis and treatment of breast cancer 1, 2 used in clinical practice in Germany. The ABC consensus is based on the votes of the ABC panelists in Lisbon.


2021 ◽  
Author(s):  
Feifei Yan ◽  
Qi Jiang ◽  
Mengye He ◽  
Peng Shen

Background: We conducted this meta-analysis to compare the efficacy and safety of PARP inhibitors with or without chemotherapy versus chemotherapy alone for advanced breast cancer. Methods: A meta-analysis and trial sequential analysis were performed using RevMan 5.2 analysis software. Results: Six eligible randomized clinical trials involving 2080 patients were included. Regimens containing PARP inhibitors were significantly associated with higher objective response rate, longer progression-free survival and overall survival. The PARP inhibitor regimen group had a significantly higher rate of grade ≥3 thrombocytopenia than the chemotherapy-only group. Conclusion: Regimens containing PARP inhibitors are effective and safe for BRCA-mutated advanced breast cancer patients. The efficacy appears to be only marginal in patients with BRCA status unselected.


Oncotarget ◽  
2018 ◽  
Vol 9 (94) ◽  
pp. 36720-36721
Author(s):  
Marina Cazzaniga ◽  
Claudio Verusio ◽  
Mariangela Ciccarese ◽  
Alberto Fumagalli ◽  
Donata Sartori ◽  
...  

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 269-269
Author(s):  
Neda Stjepanovic ◽  
Sonal Gandhi ◽  
William Tran ◽  
Alia Thawer ◽  
Ellen Warner

269 Background: Patients with hormone-receptor positive advanced breast cancer (ABC) often require palliative radiation therapy (RT) while receiving systemic treatment with CDK4/6 inhibitors (CDK4/6i). There are conflicting reports in the literature regarding whether concurrent administration of CDK4/6i and RT increases RT or hematologic toxicity and there are currently no formal guidelines for this realm. A Canadian national survey was conducted to evaluate local practice patterns of CDK4/6i management during palliative RT. Methods: An anonymized online survey was distributed to 162 Canadian breast cancer health care professionals between November 2020 and January 2021. The survey collected provider demographics and questions regarding practice, experiences and opinions on CDK4/6i management during palliative RT for ABC. Results: The survey was completed by 76 (47%) of the invited participants: 40% were medical oncologists, 26% radiation oncologists, 16% pharmacists and 18% nurses, physician assistants or radiation therapists. Nine provinces were represented. The respondents' clinical practice settings were predominantly at an academic/cancer centre (84%), while 16% of clinicians were based at a community setting. Interrupting the CDK4/6i during RT was recommended always by 21% of respondents, sometimes by 46% and never by 9%, while 24% had no opinion. The majority of opinions were based on personal experience (55%), colleagues’ practice (37%), medical literature (33%) and experience with chemotherapy agents (18%). Unexpected RT toxicity observed in patients on concomitant CDK4/6i was reported by 9% of respondents and prolonged cytopenias by 15%. Among responders who always or sometimes interrupt CDK4/6i during palliative RT, the timeframe to hold CDK4/6i prior to RT was 4-7 days 45%, 1-3 days 32%, 8-14 days 13% and 10% were unsure. Responses were similar for the timeframe used to resume the drug after RT. The majority (94%) thought that advising the patient on what to do with the CDK4/6i during RT was the role of the Medical Oncologist, while 48% also thought it was the role of the Radiation Oncologist. 23% of respondents though the patient should always be reassessed prior to restarting the CDK4/6i; 45% said sometimes, and 29% said not necessary. 82% of respondents indicated a standardized protocol or guideline would be valuable in this setting. Conclusions: Two thirds of Canadian breast cancer specialists sometimes or routinely interrupt CDK4/6i treatment during RT with 15% having observed increased toxicity with concurrent administration. Consensus guidelines for the management of CDK4/6i and RT are necessary to reduce treatment variability and improve the quality and safety of care for these patients.


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