TY - JOUR
T1 - Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma
AU - O'Malley, David M.
AU - Oza, Amit M.
AU - Lorusso, Domenica
AU - Aghajanian, Carol
AU - Oaknin, Ana
AU - Dean, Andrew
AU - Colombo, Nicoletta
AU - Weberpals, Johanne I.
AU - Clamp, Andrew R.
AU - Scambia, Giovanni
AU - Leary, Alexandra
AU - Holloway, Robert W.
AU - Gancedo, Margarita Amenedo
AU - Fong, Peter C.
AU - Goh, Jeffrey C.
AU - Swisher, Elizabeth M.
AU - Maloney, Lara
AU - Goble, Sandra
AU - Lin, Kevin K.
AU - Kwan, Tanya
AU - Ledermann, Jonathan A.
AU - Coleman, Robert L.
N1 - Publisher Copyright:
© 2022
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Objective: ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib. Methods: Patients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association with exceptional benefit (progression-free survival ≥2 years) versus progression on first scan (short-term subgroup) and other efficacy outcomes. Results: Rucaparib treatment was significantly associated with exceptional benefit compared with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline clinical characteristics and with carcinomas harboring molecular evidence of homologous recombination deficiency (HRD). A comparison between patients who derived exceptional benefit from rucaparib and those in the short-term subgroup revealed both clinical markers (no measurable disease at baseline, complete response to latest platinum, longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with exceptional benefit. Conclusions: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics or molecular features associated with HRD. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with recurrent high-grade ovarian carcinoma.
AB - Objective: ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib. Methods: Patients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association with exceptional benefit (progression-free survival ≥2 years) versus progression on first scan (short-term subgroup) and other efficacy outcomes. Results: Rucaparib treatment was significantly associated with exceptional benefit compared with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline clinical characteristics and with carcinomas harboring molecular evidence of homologous recombination deficiency (HRD). A comparison between patients who derived exceptional benefit from rucaparib and those in the short-term subgroup revealed both clinical markers (no measurable disease at baseline, complete response to latest platinum, longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with exceptional benefit. Conclusions: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics or molecular features associated with HRD. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with recurrent high-grade ovarian carcinoma.
KW - Genomics
KW - Ovarian carcinoma
KW - Rucaparib
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85140575072&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2022.08.021
DO - 10.1016/j.ygyno.2022.08.021
M3 - Article
C2 - 36273926
AN - SCOPUS:85140575072
SN - 0090-8258
VL - 167
SP - 404
EP - 413
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -