ROLE OF CDK4/6 INHIBITORS IN METASTATIC HORMON POSITIVE HER2 NEGATIVE BREAST CANCER TREATMENT

Autori:

Marija Ban, Ante Strikić, Branka Petrić Miše, Eduard Vrdoljak

Sažetak
Primjena inhibitora CDK4/6 u liječenju hormonski ovisnoga metastatskog raka dojke negativnog na HER-2 dovela je do bitnog poboljšanja kontrole bolesti, i to ponajprije znatnim produljenjem preživljenja bez progresije bolesti, uz prihvatljiv profil toksičnosti. Osnovno djelovanje inhibitora CDK4/6 jest odgađanje razvoja rezistencije na endokrinu terapiju, odnosno reverziju već nastale rezistencije. Medijani preživljenja bez progresije bolesti kreću se oko 20 i više mjeseci u prvoj liniji liječenja i 10-ak mjeseci i više u drugoj liniji. U prvoj liniji liječenja kombinirani su s aromataznim inhibitorima, a u drugoj s fulvestrantom. Produljenjem vremena bez napredovanja bolesti odgađa se primjena kemoterapije, a bolesnicama se osigurava bolja kvaliteta života. Zbog svega navedenoga ovi lijekovi u kombinaciji s endokrinom terapijom nova su, visokovrijedna terapijska opcija u liječenju metastatskog raka dojke. Međutim, ostaju brojna otvorena pitanja za svakodnevnu kliničku praksu kao što su optimalan odabir bolesnica za prvolinijsko i drugolinijsko liječenje, sekvenciranje drugih lijekova nakon progresije bolesti na inhibitore CDK4/6 te dostupnost i cijena liječenja.
Summary

Implementation of CDK4/6 inhibitors in metastatic hormone receptor positive, HER2 negative breast cancer treatment significantly improves progression free survival. CDK4/6 inhibitors are characterized by favorable toxicity profile. CDK4/6 inhibitor administration delays and/or overcomes endocrine therapy resistance in metastatic breast cancer. CDK4/6 inhibitors were tested in both first line treatment in combination with aromatase inhibitors, and in second line treatment in combination with fulvestrant. Progression free survival longer than 20 months in the first and longer than 10 months in the second treatment line has been achieved. Progression free survival prolongation may delay chemotherapy administration and consequently enable longer period with maintained quality of life. CDK4/6 inhibitors in combination with endocrine therapy represent a new valuable treatment option for metastatic hormone receptor positive HER2 negative breast cancer. However , many questions such as optimal patient selection as well as positioning of the CDK4/6 inhibitors and other endocrine therapy options during the course of metastatic disease treatment, remain unanswered. Furthermore, availability and cost of CDK4/6 inhibitors are also important issues.