Efficacy and safety of alpelisib in patients with HR+HER2-negative metastatic breast cancer in real clinical practice: Results of a single-center observational retrospective study

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Background. The combination of alpelisib with fulvestrant is the optimal targeted endocrine therapy for patients with hormone-positive (HR+) HER2-negative (HER2-) metastatic breast cancer (mBC) with mutations in the PIK3CA gene. This regimen has been shown to be highly effective in large phase II and III studies. However, randomized clinical trials cannot fully cover all possible clinical populations of pre-treated patients. Therefore, the real-world study of the efficacy and safety of the alpelisib + fulvestrant is warranted.

Aim. A retrospective analysis of the real-world efficacy and safety of alpelisib in patients with pre-treated luminal HER2- mBC.

Materials and methods. The study included 33 patients diagnosed with HR+ HER- mBC who received alpelisib in combination with fulvestrant in routine practice from 2020 to 2023. Twelve (36.4%) patients had a mutation in exon 9 of the PIK3CA gene, and 21 (63.6%) patients had a mutation in exon 20. Alpelisib was administered to pre-treated patients in different therapy lines: the median number of mBC treatment lines before alpelisib was 5 (1–8), 1 patient received alpelisib in line 1, 4 in line 2, 6 in line 3, 5 in line 4, 8 in line 5, 1 in line 6, 7 in line 7, and 1 in line 8. Patients with luminal B-type BC accounted for 72.7% (n=24). The ECOG status of 0, 1, and 2 points had 9.1%, 75.7%, and 15.2% of patients, respectively.

Results. The median overall survival was 14.0±2.5 months (95% confidence interval 9–18.9), and the median progression-free survival was 6.0±2.7 months (95% confidence interval 0.7–11.3). The prognostic factor was an interruption of drug therapy for any reason, which increased the risk of mortality. The adverse event profile was consistent with data from previous randomized trials.

Conclusion. The outcomes of therapy with alpelisib and fulvestrant show the effectiveness of this regimen in real-world settings in patients with HR+ HER2- advanced BC with a somatic mutation in the PIK3CA gene.

作者简介

Alexander Sultanbaev

Republican Clinical Oncology Dispensary; Bashkir State Medical University

编辑信件的主要联系方式.
Email: rkodrb@yandex.ru
ORCID iD: 0000-0003-0996-5995

Cand. Sci. (Med.)

俄罗斯联邦, Ufa; Ufa

Irina Kolyadina

Russian Medical Academy of Continuous Professional Education; Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology

Email: irinakolyadina@yandex.ru
ORCID iD: 0000-0002-1124-6802

  1. D. Sci. (Med.)

 

俄罗斯联邦, Moscow; Moscow

Konstantin Menshikov

Republican Clinical Oncology Dispensary; Bashkir State Medical University

Email: kmenshikov80@bk.ru
ORCID iD: 0000-0003-3734-2779

Cand. Sci. (Med.), oncologist

俄罗斯联邦, Ufa; Ufa

Shamil Musin

Republican Clinical Oncology Dispensary

Email: musin_shamil@mail.ru
ORCID iD: 0000-0003-1185-977X

Cand. Sci. (Med.), Department Head

俄罗斯联邦, Ufa

Ainur Nasretdinov

Republican Clinical Oncology Dispensary

Email: rkodrb@yandex.ru
ORCID iD: 0000-0001-8340-7962

oncologist, Department Head

俄罗斯联邦, Ufa

Nadezda Sultanbaeva

Republican Clinical Oncology Dispensary

Email: nd.sultan@rambler.ru
ORCID iD: 0000-0001-5926-0446

oncologist, Republican Clinical Oncology Dispensary

俄罗斯联邦, Ufa

Radmir Rakhimov

Republican Clinical Oncology Dispensary

Email: radmir-rr@mail.ru
ORCID iD: 0000-0002-2488-597X

Cand. Sci. (Med.), oncologist

俄罗斯联邦, Ufa

Danila Lipatov

Bashkir State Medical University

Email: lipatov911@gmail.com
ORCID iD: 0000-0002-3193-9008

Student

俄罗斯联邦, Ufa

Irina Menshikova

Bashkir State Medical University

Email: i-menshikova@bk.ru
ORCID iD: 0000-0002-8665-8895

Cand. Sci. (Med.), Assoc. Prof.

俄罗斯联邦, Ufa

Adel Izmailov

Republican Clinical Oncology Dispensary

Email: izmailov75@mail.ru
ORCID iD: 0000-0002-8461-9243

D. Sci. (Med.)

俄罗斯联邦, Ufa

Elena Lipatova

Bashkir State Medical University

Email: lipatovoleg@bk.ru
ORCID iD: 0000-0003-2588-3033

Cand. Sci. (Med.), Bashkir State Medical University

俄罗斯联邦, Ufa

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2. Fig. 1. Progression-free survival with alpelisib plus fulvestrant.

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3. Fig. 2. OS during alpelisib therapy in overall patients.

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4. Fig. 3. OS rates depending on the subtype of breast cancer.

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5. Fig. 4. OS rates depending on the mutation site.

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6. Fig. 5. OS rates depending on the timing of alpelisib interruption.

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7. Fig. 6. PR for alpelisib + fulvestrant therapy according to PET/CT: metastatic lesions in the lungs, in the left humerus, in the left femur and in the lumbar vertebra are determined.

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8. Fig. 7. PR for alpelisib + fulvestrant therapy in the brain: in the right cerebellar hemisphere, there are two cystic lesions of irregular shape, with a solid peripheral component and lumpy uptake of the contrast agent, observed as an unevenly thickened rim up to 10 mm, without perifocal edema; their size decreased from 35×36 mm to 24×14 mm and from 16×25 to 11×20 mm.

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