Piqray – basic questions at the start: whom to test? whom to treat? how to treat? Event review of the satellite symposium. RUSSCO Big Conference «Breast Cancer» (online). January 29th, 2021

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Abstract

A Satellite Symposium of Novartis Pharma was held on January 29th, 2021, within the framework of the RUSSCO Big Conference «Breast Cancer». It was dedicated to the diagnostics and treatment of patients with hormone-dependent HER2-negative advanced breast cancer (HR+ HER2- aBC) with a PIK3CA mutation using target drug Piqray (alpelisib). Experts-oncologists discussed the diagnostics of the PIK3CA mutation, data from clinical studies of alpelisib, characteristics of patients who may benefit from the alpelisib, prevention and control of adverse events that may develop during therapy with alpelisib. For planning anticancer therapy using alpelisib in combination with fulvestrant, all patients with HR+ HER2- aBC should be tested for PIK3CA mutation at the first signs of a metastatic process. Data from clinical trials demonstrate that this combination provides approximately 2-fold increase in median progression free survival compared to a placebo + fulvestrant combination. Alpelisib can be prescribed to patients with HR+ HER2- aBC with a PIK3CA mutation after progression on endocrine therapy, in a combined mode. The main adverse events – hyperglycemia and rash – are associated with the mechanism of alpelisib action, and are predictable and manageable.

References

  1. Garcia-Echeverria C, Sellers W. Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene 2008; 27 (41): 5511–26. doi: 10.1038/onc.2008.246
  2. Hennessy B, Smith D, Ram P, et al. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005; 4 (12): 988–1004. doi: 10.1038/nrd1902
  3. Arthur L, Turnbull AK, Renshaw L, et al. Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer. Breast Cancer Res Treat 2014; 147: 211–9.
  4. Friedman LS, Edgar KA, Song K, et al. The PI3K inhibitor, taselisib, has enhanced potency in PIK3CA mutant models through a unique mechanism of action. SABCS 2016; Abstract S6-04.
  5. Baselga J, Cortés J, De Laurentiis M, et al. SANDPIPER: Phase III study of the PI3-kinase inhibitor taselisib (GDC-0032) plus fulvestrant in patients with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer enriched for patients with PIK3CA-mutant tumors. SABCS 2015; Abstract OT1-03-14.
  6. Available at: https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed: 19.11.2020.
  7. Cardoso F, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol 2020; 321 (12): 1623–49. doi: 10.1016/j.annonc.2020.09.010
  8. Стенина М.Б., Жукова Л.Г., Королева И.А., и др. Практические рекомендации по лекарственному лечению рака молочной железы. Злокачественные опухоли. 2020; 10 (3s2). Режим доступа: https://rosoncoweb.ru/standarts/RUSSCO/2020/2020-09.pdf [Stenina MB, Zhukova LG, Koroleva IA, et al. Practical recommendations for drug treatment of breast cancer. Malignant Tumors. 2020; 10 (3s2). Available at: https://rosoncoweb.ru/standarts/RUSSCO/2020/2020-09.pdf (in Russian)].
  9. Rugo H, Mayer I, Conte P, et al. Prevalence of PIK3CA mutations in patients with hormone receptor-positive, human epidermal growth factor-2-negative advanced breast cancer from the SOLAR-1 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019; 79 (13 Suppl): Abstract nr CT142.
  10. Courtney KD, Corcoran RB, Engelman JA et al. The PI3K pathway as drug target in human cancer. J Clin Oncol 2010; 28 (6): 1075–83.
  11. Dienstmann R, Rodon J, Serra V, Tabernero J. Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther 2014; 13 (5): 1021–31.
  12. Fritsch C, Huang A, Chatenay-Rivauday C, et al. Characterization of the novel and specific PI3Ka inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther 2014; 13 (5): 1117–29.
  13. Andre F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019; 380: 1929–40. doi: 10.1056/NEJMoa1813904
  14. Andre F, Ciruelos EM, Juric D, 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/annonc/annonc325
  15. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with PIK3CA-mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results. J Clin Oncol 2020; 38 (Suppl. 15): Abstract 1006.
  16. Turner S, et al. ESMO 2020. Presentation # 309P. E-poster.
  17. Juric D, Loibl S, Andre F, et al. Alpelisib (ALP) with fulvestrant (FUL) in patients (pts) with PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC): Primary or secondary resistance to prior endocrine therapy (ET) in the SOLAR-1 trial. J Clin Oncol 2019; 37 (Suppl. 15): Abstract 1038.
  18. Мазурина Н.В., Артамонова Е.В., Белоярцева М.Ф., и др. Консенсус по профилактике и коррекции гипергликемии у пациентов, получающих терапию препаратом алпелисиб. Современная Онкология. 2020; 22 (4): 56–9 [Mazurina NV, Artamonova EV, Beloyartseva MF, et al. The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib. Journal of Modern Oncology. 2020; 22 (4): 56–9 (in Russian)]. doi: 10.26442/18151434.2020.4.200566
  19. Rugo HS, André F, Yamashita T, et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol 2020; 31 (8): 1001–10. doi: 10.1016/j.annonc.2020.05.001
  20. Świderska E, Strycharz J, Wroblewski A, et al. Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake. 2018. doi: 10.5772/intechopen.80402

Supplementary files

Supplementary Files
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1. JATS XML
2. Assessment of risk factors for the development of hyperglycemia prior to alpelisib initiation [18].

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