Olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: secondary safety results from the phase II LIGHT study

Abstract

Objectives: LIGHT (NCT02983799) evaluated olaparib treatment in patients with platinum-sensitive relapsed (PSR) ovarian cancer by BRCA mutation (BRCAm) and homologous recombination repair deficiency (HRD) status; the primary analysis demonstrated objective response rates (ORRs) of 69%, 64%, 29%, and 10% in cohorts of patients with a germline (g) BRCAm, with tumors with somatic (s) BRCAm, HRD-positive (non-BRCAm), and HRD-negative status, respectively (Cadoo K et al. ASCO 2020). Here, we report pre-specified secondary efficacy endpoints and subgroup analyses. Methods: In this open-label, non-randomized study, patients with PSR ovarian cancer and ≥1 prior line of platinum-based chemotherapy received olaparib monotherapy (300 mg bid). Patients were assigned to one of four cohorts based on whether they had a gBRCAm, tumors with sBRCAm, had HRD-positive (non-BRCAm) tumors, or HRD-negative tumors. Testing for gBRCAm was completed using Myriad BRACAnalysis CDx; sBRCAm testing was done with Myriad myChoice CDx. Genomic instability (GI) was assessed using the Myriad myChoice HRD test; tumors were deemed HRD-positive if they had a GI score ≥42. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and cancer antigen (CA)-125 response. Time to any progression (TTAP) was calculated from the date of the first dose of olaparib until the earliest date of RECIST v1.1 or CA-125 disease progression, or death. Results: Conclusions: Secondary efficacy data and subgroup analyses from the LIGHT study of olaparib monotherapy as treatment for PSR ovarian cancer support the primary analysis. Efficacy was observed in all cohorts, particularly in the gBRCAm and sBRCAm cohorts, where similar efficacy was observed. For patients without a BRCAm, greater efficacy was seen in the HRD-positive cohort. LIGHT (NCT02983799) evaluated olaparib treatment in patients with platinum-sensitive relapsed (PSR) ovarian cancer by BRCA mutation (BRCAm) and homologous recombination repair deficiency (HRD) status; the primary analysis demonstrated objective response rates (ORRs) of 69%, 64%, 29%, and 10% in cohorts of patients with a germline (g) BRCAm, with tumors with somatic (s) BRCAm, HRD-positive (non-BRCAm), and HRD-negative status, respectively (Cadoo K et al. ASCO 2020). Here, we report pre-specified secondary efficacy endpoints and subgroup analyses. In this open-label, non-randomized study, patients with PSR ovarian cancer and ≥1 prior line of platinum-based chemotherapy received olaparib monotherapy (300 mg bid). Patients were assigned to one of four cohorts based on whether they had a gBRCAm, tumors with sBRCAm, had HRD-positive (non-BRCAm) tumors, or HRD-negative tumors. Testing for gBRCAm was completed using Myriad BRACAnalysis CDx; sBRCAm testing was done with Myriad myChoice CDx. Genomic instability (GI) was assessed using the Myriad myChoice HRD test; tumors were deemed HRD-positive if they had a GI score ≥42. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and cancer antigen (CA)-125 response. Time to any progression (TTAP) was calculated from the date of the first dose of olaparib until the earliest date of RECIST v1.1 or CA-125 disease progression, or death. Secondary efficacy data and subgroup analyses from the LIGHT study of olaparib monotherapy as treatment for PSR ovarian cancer support the primary analysis. Efficacy was observed in all cohorts, particularly in the gBRCAm and sBRCAm cohorts, where similar efficacy was observed. For patients without a BRCAm, greater efficacy was seen in the HRD-positive cohort.