Maintenance olaparib after platinum-based chemotherapy in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Efficacy by surgical and tumor status in the Phase III SOLO1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5541-5541 ◽  
Author(s):  
Cara Amanda Mathews ◽  
Kathleen N. Moore ◽  
Nicoletta Colombo ◽  
Giovanni Scambia ◽  
Byoung-Gie Kim ◽  
...  
Keyword(s):  
Residual Disease ◽  
Brca Mutation ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Timing Of Surgery ◽  
Phase Iii ◽  
Case Report Form ◽  
Newly Diagnosed ◽  
Platinum Based Chemotherapy

5541 Background: In SOLO1 (NCT01844986), maintenance olaparib significantly improved progression-free survival (PFS) vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. N Engl J Med 2018) in pts with newly diagnosed advanced OC and a BRCAm. This analysis evaluates olaparib efficacy by timing of surgery, presence of residual tumor following surgery and response status after completion of chemotherapy in SOLO1. Methods: Pts underwent cytoreductive surgery and were in clinical complete response (CR) or partial response (PR) after platinum-based chemotherapy. Pts were stratified by response and received olaparib tablets 300 mg twice daily or placebo. Investigator-assessed PFS and objective response were assessed using modified RECIST v1.1. Results: 260 pts were randomized to olaparib and 131 to placebo; one pt did not receive placebo. Median follow-up was 41 months in both arms. 63% and 35% of pts underwent upfront and interval surgery, 21% and 76% had residual and no residual macroscopic disease after surgery, and 74% and 26% entered the study in clinical CR and PR (based on electronic case report form [eCRF] data). PFS was significantly improved regardless of the timing of surgery, residual disease status after surgery or response after platinum-based chemotherapy (Table). In pts with baseline radiologic evidence of disease (n=80; eCRF), the objective response rate was 43% for olaparib (CR, 28%) and 23% for placebo (CR, 12%). Conclusions: Maintenance olaparib improved outcomes compared with placebo in pts with newly diagnosed advanced OC and a BRCAm, regardless of surgical or tumor status. Clinical trial information: NCT01844986. [Table: see text]

scholarly journals Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

2020 ◽  
Vol 38 (30) ◽  
pp. 3528-3537
Author(s):  
Paul DiSilvestro ◽  
Nicoletta Colombo ◽  
Giovanni Scambia ◽  
Byoung-Gie Kim ◽  
Ana Oaknin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Interval Surgery

PURPOSE In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors. PATIENTS AND METHODS Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status ( BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate. RESULTS The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively. CONCLUSION Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.

Efficacy of maintenance olaparib for newly diagnosed, advanced ovarian cancer patients (pts) by BRCA1 or BRCA2 mutation in the phase III SOLO1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5551-5551
Author(s):  
Michael Friedlander ◽  
Kathleen N. Moore ◽  
Nicoletta Colombo ◽  
Giovanni Scambia ◽  
Byoung-Gie Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Statistical Tests ◽  
Brca2 Mutation ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Data ◽  
Newly Diagnosed ◽  
Brca1 And Brca2 ◽  
Platinum Based Chemotherapy

5551 Background: In SOLO1 (NCT01844986), maintenance olaparib resulted in a significant improvement in progression-free survival (PFS) for newly diagnosed, BRCA1- and/or BRCA2-mutated, advanced ovarian cancer pts compared with placebo (HR 0.30, 95% CI 0.23–0.41; median not reached vs 13.8 months; Moore et al. N Engl J Med 2018). We investigated PFS in SOLO1 for the subgroups of pts with BRCA1 mutations ( BRCA1m) or BRCA2 mutations ( BRCA2m). Methods: All pts were in clinical complete or partial response to platinum-based chemotherapy and were randomized to maintenance olaparib (300 mg twice daily; tablets) or placebo. After 2 years, pts with no evidence of disease discontinued study treatment, but pts with evidence of disease could continue study treatment. PFS by BRCAm was a predefined analysis. BRCAm were identified by central germline (Myriad or BGI) or local testing; Foundation Medicine testing confirmed tumor BRCAm. Results: Median follow-up for PFS was ~41 months in the olaparib and placebo arms. Of 391 randomized pts, 282 had BRCA1m (72%), 106 had BRCA2m (27%) and three (1%) had both (Table). Two pts in the olaparib arm had somatic BRCAm (one BRCA1m, one BRCA2m); all others had germline BRCAm. At the primary data cut-off, 155 pts in the BRCA1-mutated group (55%), 43 in the BRCA2-mutated group (41%) and none in the BRCA1/2 -mutated group had disease progression. The percentage of BRCA1-mutated pts who received olaparib and were progression-free at 1, 2 and 3 years was 86%, 69% and 53% (vs 52%, 36% and 26% receiving placebo) and for BRCA2-mutated pts was 92%, 85% and 80% (vs 50%, 32% and 29%, respectively). Conclusions: Significant PFS benefit with olaparib versus placebo was demonstrated for all pts, regardless of whether they had BRCA1m or BRCA2m. Statistical tests were not used to compare BRCA1- and BRCA2-mutated pts, but those with BRCA2m appeared to receive greater benefit from maintenance olaparib than those with BRCA1m. Clinical trial information: NCT01844986. [Table: see text]

Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5539-5539
Author(s):  
Nicoletta Colombo ◽  
Kathleen N. Moore ◽  
Giovanni Scambia ◽  
Ana Oaknin ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Brca Mutation ◽  
Supportive Therapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Free Survival ◽  
First Onset ◽  
Clinical Trial Information

5539 Background: In SOLO1 (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit vs placebo in newly diagnosed pts with advanced OC, a BRCAm and clinical complete or partial response to platinum therapy (HR 0.30; 95% CI 0.23–0.41) and was well tolerated (Moore et al. NEJM 2018). We analysed the most common AEs and hematologic AEs in SOLO1. Methods: Pts received olaparib tablets 300 mg twice daily or placebo until progression unless they had no evidence of disease at 2 years, in which case treatment stopped. AEs were graded using CTCAE v4.0. Results: Of 391 pts randomized, 390 (olaparib, 260; placebo, 130) were treated and included in the safety analysis. Median treatment duration was approximately 25 months for olaparib vs 14 for placebo. Median time to first onset of the most common AEs (nausea, vomiting, fatigue/asthenia, anemia) and neutropenia and thrombocytopenia was < 3 months; the first event lasted a median of < 2 months, apart from fatigue/asthenia, which lasted a median of < 4 months (Table). AEs were usually managed with supportive therapy and/or dose modification; few pts discontinued. Conclusions: AEs in newly diagnosed pts with advanced OC treated with olaparib usually occurred early and were manageable, with few discontinuations. Clinical trial information: NCT01844986. [Table: see text]

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Andres Poveda ◽  
Stephanie Lheureux ◽  
Nicoletta Colombo ◽  
David Cibula ◽  
Kristina Lindemann ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib ◽  
Grade 3

5545 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]

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