Alpelisib for the treatment of HR+HER2-metastatic breast cancer in patients with the PIK3CA mutation: results of the SOLAR-1 study


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Abstract

Determination of the PIK3CA+ gene mutation made it possible to isolate a special group of patients with PIK3CA+HR+HER2 advanced breast cancer (PIK3CA+HR+HER2-aBC) who receive the most benefit from molecularly targeted anti-PI3K therapy. Activating PIK3CA gene mutations are found in 40% of patients and are associated with an unfavorable course of metastatic breast cancer (mBC). Alpelisib is a selective inhibitor of the а-isoform of phosphatidylinositol-3-kinase (PI3K), which plays a key role in the pathogenesis of breast cancer. According to the SOLAR-1 study, the addition of the targeted drug alpelisib to endocrine therapy with fulvestrant in patients with PIK3CA+HR+HER2-aBC statistically significantly increased progression-free survival from 5.7 to 11.0 months (hazard ratio 0.65; 95% confidence interval - 0.50-0.85, p<0.001). Hyperglycemia and rash are the main predictable and manageable side complications of alpelisib therapy; grade 3-4 of such side effects was recorded in 36.6 and 9.9% of cases, respectively. Also, based on the results of the SOLAR-1 study, a profile of BC patients for whom the appointment of alpelisib is vital was identified. These are patients with PIK3CA+HR+HER2-aBC with progression on previous therapy with aromatase inhibitors as monotherapy or in combination with CDK4/6 inhibitors, taking into account possible resistance to endocrine therapy (primary or secondary). Given the significant role of the PIK3CA gene mutation in the pathogenesis of breast cancer, its high incidence and the presence of appropriate biologically targeted anti-PIK3 therapy, before planning treatment for aBC patients in routine clinical practice, it is necessary to determine the PIK3CA gene mutation in addition to the determination of expression of estrogen and progestorone receptors and HER2/neu in the tumor.

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About the authors

T. Yu Semiglazova

N.N. Petrov National Medical Research Center of Oncology; North-Western State Medical University n.a. I.I. Mechnikov

Email: tsemiglazova@mail.ru
Dr. Sci. (Med.), Associate Professor, Head of the Division - Leading FResearcher at the Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, Petrov NMRC of Oncology, Professor at the Department of Oncology, North-Western State Medical University n.a. I.I. Mechnikov 68 Leningradskaya str., Pesochny settlment, St. Petersburg 197758, Russian Federation

V. V Semiglazov

N.N. Petrov National Medical Research Center of Oncology; First Pavlov State Medical University

St. Petersburg, Russia

V. V Klimenko

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

N. A Brish

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

Yu. V Alekseeva

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

V. A Klyuge

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

A. A Krutov

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

R. M Paltuev

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

B. S Kasparov

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

P. V Krivorotko

N.N. Petrov National Medical Research Center of Oncology; North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

V. F Semiglazov

N.N. Petrov National Medical Research Center of Oncology; North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

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