Possibilities of overcoming hormone resistance in patients with metastatic HR+ HER2- breast cancer using the drug alpelisib in various subgroups in real clinical practice

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Abstract

Background. Despite significant advances in the treatment of metastatic luminal breast cancer, this disease remains the most common cause of death from malignant neoplasms in women. One of the most common causes of hormone resistance is the PIK3CA mutation, which occurs in 40% of patients and is a factor of poor prognosis. Since 2020, the targeted drug alpelisib in combination with fulvestrant has been used to treat mBC with the PIK3CA mutation. As practical experience with the use of alpelisib accumulates, data on the effectiveness and tolerability of therapy in various subgroups of patients are emerging.

Objective. Evaluation of the effectiveness of combination hormone therapy in patients with PIK3CA mutation in real clinical practice.

Methods. A retrospective analysis of the treatment of 38 patients in St. Petersburg City Clinical Oncology Dispensary in the period from 04.2021 to 08.2023 was carried out. Progression-free survival was chosen as the reference point. Stratification factors included line of use of alpelisib, previous therapy and duration of treatment with CDK4/6 inhibitors, history of chemotherapy use. Median line of alpelisib use = 3.

Results. Median PFS in the overall population was 6 months, 6-month PFS 50%; 12-month PFS 34%. When using alpelisib in 2-3 lines, mPFS was 8.0 months, when used in 4 and subsequent lines – 5 months. In patients who had previously received chemotherapy for mBC, mPFS was 4 months; in patients who had not received chemotherapy, it was 12.0 months. In patients who had previously received a CDK4/6 inhibitor, mPFS was 6.0 months; in patients without a history of of use of CDK4/6 inhibitor, mPFS was 7.0 months. In patients with a response to a CDK4/6 inhibitor ≥ 1 year, mPFS was 4.0 months, and in patients with a response to a CDK4/6 inhibitor <1 year, mPFS had not yet been achieved at the time of data analysis (P=0.09).

Conclusion. A study in real clinical practice confirms the effectiveness of combination hormone therapy with the inclusion of the targeted drug alpelisib in patients with the PIK3CA mutation, even when used in late lines in patients with signs of hormone resistance. The best response is achieved in patients who have not received chemotherapy for the treatment of mBC, with no history of chemotherapy for mBC, when alpelisib is prescribed in 2–3 lines.

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About the authors

R. V. Orlova

St. Petersburg State University, Faculty of Medicine, Department of Oncology; City Clinical Oncology Dispensary

Email: lok2008@list.ru
ORCID iD: 0000-0002-9368-5517
Russian Federation, St. Petersburg; St. Petersburg

M. I. Gluzman

St. Petersburg State University, Faculty of Medicine, Department of Oncology; City Clinical Oncology Dispensary

Author for correspondence.
Email: lok2008@list.ru

Cand. Sci. (Med.), Associate Professor, Department of Oncology, Faculty of Medicine, St. Petersburg State University; Head of the Department of Chemotherapy № 12 (anti-tumor drug therapy), City Clinical Oncology Dispensary

Russian Federation, St. Petersburg; St. Petersburg

A. A. Vakhitova

St. Petersburg State University, Faculty of Medicine, Department of Oncology

Email: lok2008@list.ru
ORCID iD: 0000-0003-1321-3657
Russian Federation, St. Petersburg

References

  1. Fillbrunn M., Signorovitch J., Andreé F., et al. PIK3CA mutation status, progression and survival in advanced HR + /HER2- breast cancer: a meta-analysis of published clinical trials. BMC. Cancer 2022;22:1002. doi: 10.1186/s12885-022-10078-5.
  2. Rajadurai P., et al. Abstract P5-13-25: PIK3CA registry: A noninterventional, descriptive, retrospective cohort study of PIK3CA mutations in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Cancer Res. 2022;82(Suppl. 4):P5-13-25. doi: 10.1158/1538-7445.SABCS21-P5-13-25.
  3. Andre F., et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer. N Engl J Med. 2019;380:1929–40. doi: 10.1056/NEJMoa1813904.
  4. Andre F., et al. Overall survival (os) results from SOLAR-1, a phase III study of alpelisib (ALP) + fulvestrant (FUL) for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Ann Oncol. 2020;31(Suppl. 4):S1142–215. doi: 10.1016/j.annonc.2020.11.011.
  5. Тюляндин С.А., Артамонова Е.В., Жукова Л.Г. и др. Практические рекомендации по лекарственному лечению рака молочной железы. Злокачественные опухоли: Практические рекомендации RUSSCO #3s2. 2022;12:155–97. [Tyulyandin S.A., Artamonova E.V., Zhukova L.G. and others. Practical recommendations for drug treatment of breast cancer. Malignant tumors: Practical recommendations RUSSCO #3s2. 2022;12:155–97. (In Russ.)]. doi: 10.18027/2224-5057-2022-12-3s2- 155-197.
  6. Hortobagyi G.N., Stemmer S.M., Burris H.A., et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386:942–50. doi: 10.1056/NEJMoa2114663.
  7. Slamon D.J., Neven P., Chia S., et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021;32(8):1015–24. doi: 10.1016/j.annonc.2021.05.353.
  8. Lu Y.S., Im S.A., Colleoni M., et al. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022;28(5):851–59. doi: 10.1158/1078-0432.CCR-21-3032.
  9. Sledge G., Toi M., Neven P., et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA. Oncol. 2020;6(1):116–24. doi: 10.1001/jamaoncol.2019.4782.
  10. Chia S., Neven P., Ciruelos M., et al. Alpelisib+endocrine therapy in patients with PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative, advanced breast cancer: Analysis of all 3 cohorts of the BYLieve study. J Clin Oncol. 2023;41(Suppl. 16):1078–78. doi: 10.1200/JCO.2023.41.16_suppl.1078.
  11. O’Shaughnessy J. Woeckel A., Pistilli B., et al. Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis. J Clin Oncol. 2022;40(Suppl. 16):1055–55. doi: 10.1200/JCO.2022.40.16_suppl.1055.
  12. Chia S., Ruiz-Borrego M., Drullinsky P., et al. Impact of duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy on alpelisib (ALP) benefit in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–), PIK3CA-mutated advanced breast cancer (ABC) from BYLieve. J Clin Oncol. 2021;39(Suppl. 15):1060–60. doi: 10.1200/JCO.2021.39.15_suppl.1060.
  13. Chia S., Ciruelos E.M., Rugo H.S., et al. Effect of duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy (≤6 mo or >6 mo) on alpelisib benefit in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) from BYLieve [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7–10; San Antonio, TX. Philadelphia (PA): AACR. Cancer Res. 2022;82(Suppl. 4):P1-18-08. doi: 10.1158/1538-7445.SABCS21-P1-18-08.
  14. Мазурина Н.В., Артамонова Е.В., Белоярце-ва М.Ф. и др. Консенсус по профилактике и коррекции гипергликемии у пациентов, получающих терапию препаратом алпелисиб. Современная онкология. 2020;22 (4):56–9. [Mazurina N.V., Artamonova E.V., Beloyartseva M.F. et al. Consensus on the prevention and correction of hyperglycemia in patients receiving therapy with alpelisib. Modern oncology. 2020;22(4):56–9. (In Russ.)]. doi: 10.26442/18151434.2020.4.200566.
  15. Шливко И.Л., Гаранина О.Е., Артамонова Е.В. и др. Консенсус по профилактике и коррекции сыпи у пациентов, получающих терапию препаратом алпелисиб. Современная онкология. 2021;23(4):572–6. [Shlivko I.L., Garanina O.E., Artamonova E.V. et al. Consensus on the prevention and correction of rash in patients receiving therapy with alpelisib. Modern oncology. 2021;23(4):572–6. (In Russ.)]. doi: 10.26442/18151434.2021.4.201275.
  16. Filonenko D., Zhukova L. Prophylactic use of metformin in patients on alpelisib treatment. J Clin Oncol. 2022;40(Suppl. 16):e13040–e13040. doi: 10.1200/JCO.2022.40.16_suppl. e13040.

Supplementary files

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2. Fig. 1. PFS during therapy with alpelisib in the general population (A) and depending on the line of use of alpelisib (B)

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3. Fig. 2. PFS during therapy with alpelisib in patients who have and have not previously received chemotherapy

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4. Fig. 3. PFS during therapy with alpelisib in patients who have and have not previously received a CDK4/6 inhibitor (A), and with different duration of response to previous therapy with a CDK4/6 inhibitor (B)

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