Izkušnje z zdravilom olaparib pri zdravljenju recidivnega epitelijskega raka jajčnikov z mutacijami v genih BRCA 1 in BRCA 2 Experience with olaparib in the treatment of recurrent ovarian epithelial cancer with mutations in the BRCA 1 and BRCA 2 genes

Abstract

Izhodišče: Zdravilo olaparib uporabljamo za vzdrževalno peroralno zdravljenje recidivnega epitelijskega raka jajčnikov z mutacijami v genih BRCA 1 in BRCA 2 pri bolnicah, ki se odzovejo na kemoterapijo s preparati platine.
Namen: Prikazati varnost in učinkovitost zdravljenja s poli-ADP riboza polimeraznim (PARP) inhibitorjem olaparibom v redni klinični praksi v sklopu vzdrževalnega zdravljenja recidivnega epitelijskega raka jajčnikov z mutacijami v genih BRCA 1 in BRCA 2.
Metode: V retrospektivno analizo smo vključili bolnice z recidivnim epitelijskim rakom jajčnikov z mutacijami v genih BRCA 1 in BRCA 2, ki so se začele zdraviti z olaparibom na Onkološkem inštitutu Ljubljana v obdobju od 1. novembra 2015 do 31. decembra 2020. Cilja raziskave sta bila oceniti varnost in učinkovitost zdravila olaparib (preživetje brez ponovitve bolezni, celokupno preživetje). Raziskavo je odobrila etična komisija na Onkološkem inštitutu Ljubljana.
Rezultati: V opazovanem obdobju je bilo z olaparibom zdravljenih 88 bolnic z recidivnim epitelijskim rakom jajčnikov z mutacijami v genih BRCA 1 in BRCA 2. Mediana starost bolnic je bila 60 let. Večina (61 %) je imela prvi recidiv bolezni, prav tako večina (74 %) je imela tudi zarodno mutacijo v genu BRCA 1. Večina bolnic (85 %) je nadalje imela vsaj en neželeni učinek zdravljenja z olaparibom. Najpogostejši (vse stopnje) so bili: slabost (59 %), utrujenost (59 %), anemija (25 %), dispepsija (14 %), tekoče blato (11 %), spremembe okusa (10 %), nevtropenija (6 %) in aritmija (1 %). Resne neželene učinke (stopnje 3/4) je imelo 10 % bolnic: pojavljali sta se anemija (9 %) in slabost (1 %). Mediani čas sledenja je bil 40 mesecev. Mediano preživetje brez ponovitve bolezni je bil 14,3 meseca, mediano celokupno preživetje pa 20,4 meseca. Preživetje brez napredovanja bolezni je bilo odvisno od vrste mutacije v genih BRCA: pri somatski mutaciji v genih BRCA 1/2 je bilo 80 % bolnic brez progresa bolezni, pri zarodni mutaciji BRCA 2 je bilo teh 55 % bolnic, pri zarodni mutaciji BRCA 1 pa 32 % (p = 0,021). Vrsta mutacije v genih BRCA 1/2 ni imela vpliva na celokupno preživetje bolnic.

Abstract (Eng)

Introduction: Olaparib is used as maintenance oral therapy of patients with BRCA 1/2 mutated relapsed epithelial ovarian cancer.
Aim of study: To evaluate the safety and efficacy of olaparib in treatment of patients with BRCA 1/2 mutated relapsed epithelial ovarian cancer.
Methods: Retrospective analysis of patients with BRCA 1/2 mutated relapsed epithelial ovarian cancer treated with olaparib at the Institute of Oncology Ljubljana in the period from 1st november 2015 to 31th december 2020. The end points of the study were safety and efficacy (progression-free survival, overall survival). The study was approved by our institutional ethics board.
Results: In the observed period, a total of 88 patients with BRCA 1/2 mutated relapsed epithelial ovarian cancer were treated with olaparib. Median age of patients was 60 years. Majority of patients (61%) had 1st relapse of the disease. Majority of patients (74%) had germline BRCA 1 gene mutation. Majority of patients (85%) had at least one adverse event during olaparib treatment. The most common adverse events (all grades) were: nausea (59%), fatigue (59%), anemia (25%), dispepsia (14%), diarrhea (11%), dysgeusia (10%), neutropenia (6%) and arrhythmia (1%). Severe adverse events (grade 3/4) had 10% of patients: anemia 9%, nausea 1%. Median follow up was 40 months. Median progression-free survival was 14,3 months, median overall survival was 20,4 months. Progression-free survival was in correlation to the type of BRCA gene mutation: 80% of patients with somatic BRCA 1/2 gene mutation were progression-free, 55% of patients with germline BRCA 2 gene mutation were progression-free, while 32% of patients with germline BRCA 1 gene mutation were progression-free (p=0,021). The type fo BRCA 1/2 gene mutation did not correlate with overall survival.