A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA5500-LBA5500 ◽  
Author(s):  
Joyce Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Open Label ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5535-5535 ◽  
Author(s):  
Joyce F. Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

5535 Background: We previously reported that the combination of cediranib (ced) and olaparib (olap) improved progression-free survival (PFS) and overall response rates (ORR) in women with recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related ovarian cancer (OvCa) (NCT 01116648). We conducted an updated PFS and overall survival (OS) analysis. Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. PFS was defined as time from randomization to radiographic progression or death. OS was defined as time from randomization to death. Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). As of Dec 21, 2016, 67 pts had a PFS event, and 52 pts had an OS event. Updated median PFS was 8.2 mos for Olap and 16.5 mos for Ced/Olap (HR 0.50, 95% CI 0.30-0.83, p=0.007). Median OS was 33.3 mos for Olap and 44.2 mos for Ced/Olap (HR 0.64, 95% CI 0.36-1.11, p=0.11). Within known germline BRCA mut carriers, updated PFS was 16.5 vs 16.4 mos (HR 0.75, p=0.42), and OS was 40.1 vs 44.2 mos (HR 0.79, p=0.55) for Olap and Ced/Olap, respectively. In pts without known germline BRCA mut, updated PFS was 5.7 vs 23.7 mos (HR 0.32, p=0.002), and OS was 23.0 vs 37.8 mos (HR 0.48, p=0.074). Conclusions: Updated PFS results consistently demonstrated that Ced/Olap significantly extended PFS compared to Olap in the overall population of women with plat-sens OvCa. In this Phase 2 study not powered to detect OS diferences, there was a trend towards OS improvement with Ced/Olap, particularly in pts without a known germline BRCA mutation. Results from ongoing studies of this oral combination in OvCa are of clinical interest. Clinical trial information: NCT 01116648.

Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer: A randomized controlled chemotherapy-free study—NSGO-AVANOVA2/ENGOT-OV24.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5505-5505 ◽  
Author(s):  
Mansoor Raza Mirza ◽  
Elisabeth Avall-Lundqvist ◽  
Michael J. Birrer ◽  
Rene dePont Christensen ◽  
Gitte-Bettina Nyvang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Open Label ◽  
Once Daily ◽  
Platinum Sensitive ◽  
Patient Reported ◽  
Eortc Qlq

5505 Background: Standard treatment of platinum-sensitive recurrent ovarian cancer (PSROC) is platinum based combination chemotherapy ± bevacizumab. However, this treatment modality is hardly curative, and is associated with significant toxicity. Both bevacizumab (BEV) and PARP inhibitors (PARPi) have demonstrated efficacy in PSROC. There is preclinical evidence of enhanced activity of the combination. This is the proof-of-concept randomized trial of PARPi-BEV combination against PARPi monotherapy as treatment in PSROC, regardless of number of previous lines of therapies. Methods: In this randomized, open-label, phase 2 study, women with measurable/evaluable, high-grade serous or endometrioid PSROC were randomized to niraparib 300mg once daily or the combination of niraparib 300mg once daily and BEV 15mg/kg IV every 3 weeks until disease progression (1:1 randomization). The primary endpoint was progression-free survival (PFS). Stratification was according to homologous recombination-deficiency(HRD) status (MyChoice HRD) and chemotherapy-free-interval (CFI)(6-12months (mo) vs. >12mo). First-line maintenance bevacizumab was permitted. Results: Of 97 enrolled patients, 48 were randomized to niraparib monotherapy and 49 to the chemotherapy-free combination. The combined treatment significantly improved PFS compared to niraparib alone: median 11.9 vs. 5.5 mo; hazard ratio (HR) adjusted for stratification factors 0.35; 95% confidence interval (CI),[0.21 to 0.57]; P<0.001. Pre-planned exploratory subgroup analyses: patients with HRD-positive tumors (n=54) HR 0.36 (CI, 0.18-0.69); HRD-negative disease (n=43) HR, 0.47 (CI, 0.24-0.95); g BRCAmut patients (n=34) HR 0.53 (CI, 0.23-1.21); non-g BRCAmut patients (n=63) HR 0.33; CI, 0.18-0.61); CFI of 6 to 12 mo (n=38) HR, 0.29 (CI, 0.14 to 0.62); CFI of ≥12 mo (n=59) HR, 0.42; (CI, 0.22 to 0.80). There was no difference in treatment-emergent grade 3-4 adverse events except for the rate of hypertension (26.5% vs. 0%) and neutropenia (12.2% vs. 2.1%). Patient-reported outcomes measured using EORTC QLQ-C30 and OV28 were similar for both treatment arms. Conclusions: Both niraparib alone and the combination had meaningful activity in PSROC. Compared to niraparib alone, the chemotherapy-free regimen of niraparib and BEV significantly improved PFS in women with PSROC,regardless of HRD status and duration of CFI. Clinical trial information: NCT02354131.

scholarly journals Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1920 ◽  
Author(s):  
Paik ◽  
Lee ◽  
Lee ◽  
Shin ◽  
Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Partial Remission ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
High Grade ◽  
Platinum Sensitive

Background: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. Method: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. Results: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). Conclusions: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

2008 ◽  
Vol 26 (19) ◽  
pp. 3176-3182 ◽  
Author(s):  
Jalid Sehouli ◽  
Dirk Stengel ◽  
Guelten Oskay-Oezcelik ◽  
Alain G. Zeimet ◽  
Harald Sommer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Refractory

PurposeThe management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.Patients and MethodsWomen with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m2/d, topotecan 1.0 mg/m2plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m2/d plus gemcitabine 800 mg/m2on day 1 and 600 mg/m2on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).ResultsThe trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.ConclusionNonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): A randomized, open-label phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5001-5001 ◽  
Author(s):  
Amit M. Oza ◽  
David Cibula ◽  
Ana Oaknin ◽  
Christopher John Poole ◽  
Ron H.J. Mathijssen ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3

5001 Background: The oral PARP inhibitor olaparib has shown antitumor activity in pts with SOC. Our multicenter study compared the efficacy of (Arm A) olaparib capsules plus P/C for 6 cycles then maintenance olaparib monotherapy vs (Arm B) P/C alone for 6 cycles and no further therapy in pts with PSR SOC (NCT01081951). Methods: Pts received 6 x 21-day(d) cycles of olaparib (200 mg bid, d1–10/21) + P (175 mg/m2 iv, d1) + C (AUC4 iv, d1), then olaparib monotherapy as maintenance (400 mg bid, continuous) (Arm A), or 6 x 21d cycles of P (175 mg/m2 iv, d1) + C (AUC6 iv, d1) then no further therapy (Arm B), until progression. Randomization (1:1) was stratified by number of platinum treatments and platinum-free interval. Primary endpoint: progression-free survival (PFS) by central review (RECIST 1.1). Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Archival tissue was collected where available for analysis of biomarker correlation. Results: Of 162 pts randomized (n=81 per arm), 156 received treatment (Arm A, n=81; Arm B, n=75) and 121 began the maintenance/no further therapy phase (Arm A, n=66; Arm B, n=55). Olaparib + P/C (AUC4) followed by maintenance olaparib showed a significant improvement in PFS vs P/C (AUC6) alone (HR = 0.51, 95% CI 0.34, 0.77; P=0.0012; median = 12.2 vs 9.6 months). OS data are immature (total events: 14%). ORR was similar for Arm A and Arm B (64 vs 58%). Most common AEs during the combination phase were alopecia (74 vs 59%), nausea (69 vs 57%) and fatigue (64 vs 57%) for Arm A vs Arm B, respectively. Pts with grade ≥3 AEs (65 vs 57%), serious AEs (SAEs: 15 vs 21%) and AEs leading to treatment discontinuation (19 vs 16%) were similar for Arm A vs Arm B. Most common AEs during maintenance/no further therapy were nausea (50 vs 6%) and vomiting (29 vs 7%). 29 vs 16% of pts had grade ≥3 AEs, 9 vs 7% had SAEs and 8% vs N/A discontinued due to AEs in the olaparib vs no treatment arms, respectively. There were no fatal AEs. Conclusions: In pts with PSR SOC, olaparib plus P/C (AUC4) followed by olaparib 400 mg bid monotherapy maintenance treatment resulted in a significant improvement in PFS vs P/C (AUC6) alone.

scholarly journals Use of PARP Inhibitors for Ovarian Cancer

2021 ◽  
Vol 19 (5.5) ◽  
pp. 636-638
Author(s):  
Deborah K. Armstrong
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Resistant Disease ◽  
Relapsed Disease ◽  
Increased Activity

PARP inhibitors have been used to treat numerous diseases, but these agents have been approved the longest for use in ovarian cancer. All trials of PARP inhibitor maintenance in newly diagnosed ovarian cancer are positive for prolonged progression-free survival (PFS), but patients with BRCA mutations consistently derive the most benefit. Testing for homologous recombination deficiency may provide information regarding the degree of PFS benefit. In individuals without a BRCA mutation, PARP inhibition also prolongs PFS after chemotherapy for platinum-sensitive, PARP-naïve disease. As in the up-front setting, patients with BRCA mutations derive the most benefit in these trials. Finally, PARP inhibitors are active as monotherapy in PARP-naïve, BRCA-mutated relapsed disease, with increased activity observed in platinum-sensitive versus platinum-resistant disease.

Anlotinib plus pemetrexed as a further treatment for patients with platinum-resistant ovarian cancer: A single-arm, open-label, phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5533-5533
Author(s):  
Jueming Chen ◽  
Wei Wei ◽  
Lie Zheng ◽  
Han Li ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Open Label ◽  
Platinum Resistant ◽  
Grade 3

5533 Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.

scholarly journals PARP Inhibitor in Platinum-Resistant Ovarian Cancer: Single-Center Real-World Experience

2021 ◽  
pp. 506-511
Author(s):  
Amit Agarwal ◽  
Saphalta Baghmar ◽  
Chandragouda Dodagoudar ◽  
Suhail Qureshi ◽  
Aseem Khurana ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Partial Response ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Platinum Sensitive ◽  
Platinum Resistant ◽  
Proven Efficacy

PURPOSE Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven efficacy in treatment of BReast CAncer ( BRCA) gene mutation-positive platinum-sensitive ovarian cancers. There is paucity of data for their role in platinum-resistant ovarian cancer (PROC). We report here retrospective analysis of outcome of PARPi treatment in a group of patients including those of PROC. PATIENTS AND METHODS We analyzed all consecutive patients who received PARPi. The efficacy of PARPi monotherapy was assessed in patients with relapsed high-grade serous ovarian carcinoma with g BRCAm. The drug was procured through compassionate program. Drugs (olaparib and talazoparib) were provided in capsule form. RESULTS Between July 1, 2015, and June 30, 2019, 28 patients with ovarian cancer received PARPi. At the time of data censoring (September 30, 2019), four (14.3%) patients are still on treatment. Median age was 54.5 years (range, 39-75 years). Median number of previous lines of chemotherapy received was three (range, 1-6). Eleven platinum-sensitive patients received the drug as maintenance (five in complete response and six in partial response after chemotherapy), whereas 17 (60.7%) had platinum-resistant progressive disease while starting the drug. In PROC, objective response rate (complete response plus partial response) was 47%, median progression-free survival was 8.2 months (5.3-11.3), and overall survival was 14.9 months (11.2-18.5). No new side effects were observed. CONCLUSION This is the first study from India evaluating PARPi in platinum-resistant ovarian cancer. This study suggests that PARPi is a viable treatment option in patients with PROC with gBRCAm. This should be further evaluated in randomized clinical trial.

Efficacy and safety of olaparib according to age in BRCA-1/2 mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2 (AGO-OVAR 2.23/ENGOT-Ov21) study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6068-6068 ◽  
Author(s):  
Fabian Trillsch ◽  
Sven Mahner ◽  
Beyhan Ataseven ◽  
Rebecca Asher ◽  
Coraline Dubot ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Specific Information ◽  
Efficacy And Safety ◽  
Platinum Sensitive ◽  
Significant Difference ◽  
Brca 1

6068 Background: Adding olaparib as maintenance treatment to BRCA-1/2 mutated patients (pts) with recurrent platinum-sensitive ovarian cancer (PSOC) has significantly improved progression-free survival (PFS) as well as patient-centered endpoints. As BRCA mutated pts tend to be younger, specific information on efficacy and safety of olaparib for elderly pts is of special interest. Methods: 295 pts from the SOLO2 trial that randomly assigned to olaparib or placebo were categorized according to age cutoff at 65 years. The efficacy and tolerability of olaparib relative to placebo within in each age group was assessed based on PFS and toxicity outcomes. Quality of life (QoL) was assessed using EQ-5D-5L descriptive system score and FACT Trial Outcome Index (TOI) and evaluated using generalized estimating equations (GEE) and time without significant symptoms of toxicity (TWiST) analysis. Results: Baseline characteristics were similar in pts ≥65 years (N=62; 21%) compared to pts <65 years (N=233; 79%), except for more BRCA2 mutations in elderly pts (39% vs. 23%). There was no significant difference in the magnitude of PFS benefit from olaparib in elderly as compared with younger pts (interaction P=0.33). The PFS adjusted hazard ratio (HR) of olaparib vs. placebo arms were respectively HR≥65 0.43 (95%-confidence interval [CI] 0.24-0.81) and HR<65 0.31 (95%-CI 0.22-0.43). Elderly and younger pts also had comparable safety profiles with no significant differences in median time on olaparib treatment (≥65: 27 vs. <65: 33 months), percentage of pts experiencing at least one grade >2 adverse event with olaparib (≥65: 73% vs. <65: 79%), or requiring at least one dose interruption or dose reduction (≥65: 77.5 vs. <65: 77.6%). No differences were found with regards to QoL scores. Quality adjusted TWiST analysis showed only non-significant differences in duration of good QoL under olaparib (≥65: 8.02 vs. <65: 9.24 months, P=0.48). Conclusions: In this large cohort of BRCA mutated PSOC pts treated with a PARP inhibitor within a phase III trial, no significant differences were detected in terms of efficacy, safety, and QoL with olaparib treatment for pts ≥65 years compared to younger pts. This information supports the use of PARP inhibitors as maintenance therapy for PSOC pts irrespective of age. Clinical trial information: NCT01874353.

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