Objective AGO-OVAR 16 demonstrated that pazopanib maintenance therapy significantly increased progression-free survival (PFS) in patients with ovarian cancer whose disease had not progressed after first-line therapy. In a sub-study, we evaluated the effect of clinically important germline BRCA1 and BRCA2 mutations on PFS. Methods Of 940 AGO-OVAR 16 participants, 664 had BRCA1/2 exon sequencing data (pazopanib, n = 335; placebo, n = 329). A Cox model was used to test the association between genetic variants and PFS. Results Ninety-seven of 664 patients (15%) carried clinically important BRCA1/2 mutations (BRCA1/2 carriers: pazopanib 14%, placebo 16%). Median PFS was longer in BRCA1/2 mutation carriers than in BRCA1/2 non-carriers in the placebo arm (30.3 vs 14.1 months, hazard ratio, 0.48; 95% confidence interval [CI]: 0.29-0.78; P = 0.0031); a similar non-significant trend was noted with pazopanib (30.2 vs 17.7 months, hazard ratio, 0.64; 95% CI: 0.40-1.03; P = 0.069). Among BRCA1/2 non-carriers, PFS was longer for pazopanib-treated patients than placebo-treated patients (17.7 vs 14.1 months, hazard ratio, 0.77; 95% CI: 0.62-0.97; P = 0.024). Among BRCA1/2 carriers, there was no significant PFS difference between treatments, although numbers were small (pazopanib, 46; placebo, 51), resulting in a wide CI (hazard ratio, 1.36; 95% CI: 0.66-2.82). Conclusions Patients with clinically important BRCA1/2 mutations had better prognosis. BRCA1/2 mutation status might be added as strata in future trials in primary ovarian cancer.
Harter P., Johnson T., Berton-Rigaud D., Park S.-Y., Friedlander M., Del Campo J.M., et al. (2016). BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study. GYNECOLOGIC ONCOLOGY, 140(3), 443-449 [10.1016/j.ygyno.2015.12.027].
|Citazione:||Harter P., Johnson T., Berton-Rigaud D., Park S.-Y., Friedlander M., Del Campo J.M., et al. (2016). BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study. GYNECOLOGIC ONCOLOGY, 140(3), 443-449 [10.1016/j.ygyno.2015.12.027].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study|
|Autori:||Harter P.; Johnson T.; Berton-Rigaud D.; Park S.-Y.; Friedlander M.; Del Campo J.M.; Shimada M.; Forget F.; Mirza M.R.; Colombo N.; Zamagni C.; Chan J.K.; Imhof M.; Herzog T.J.; O'Donnell D.; Heitz F.; King K.; Stinnett S.; Barrett C.; Jobanputra M.; Xu C.-F.; Du Bois A.|
|Data di pubblicazione:||2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ygyno.2015.12.027|
|Appare nelle tipologie:||01 - Articolo su rivista|