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BACKGROUND Breast cancer patients may experience cognitive difficulties after chemotherapy. PURPOSE To investigate whether an exercise intervention can affect cerebral blood flow (CBF) in breast cancer patients and if CBF changes relate to memory function. STUDY TYPE Prospective. POPULATION Chemotherapy-treated breast cancer patients with cognitive problems, and with relatively low physical activity levels were randomized to an exercise intervention (n=91) or control group (n=90). FIELDSTRENGTH/SEQUENCE A 3-T arterial spin labeling CBF scan was performed. ASSESSMENT The 6-month intervention consisted of (supervised) aerobic and strength training, 4x1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after six months included the arterial spin labeling CBF scan, from which we calculated gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Furthermore, we measured physical fitness and memory functioning. STATISTICAL TESTS Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS We observed significant improvement in physical fitness (VO2peak) in the intervention group (n=53) compared to controls (n=51, B1.47, 95%CI:0.44; 2.50), nevertheless no intervention effects on CBF were found (e.g. whole brain: B0.98, 95%CI:-2.38; 4.34). Highly fatigued patients showed larger, but not significant, treatment effects. Additionally, change in physical fitness, from baseline to post-intervention, was positively associated with changes in CBF (e.g., whole brain: B0.75, 95%CI:0.07; 1.43). However, we observed no relation between CBF changes and change in memory performance. DATA CONCLUSION The exercise intervention did not affect CBF of cognitively affected breast cancer patients. However, a change in physical fitness was related to a change in CBF, but a change in CBF was not associated with memory functioning.

Background: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. Methods: Chemotherapy-exposed breast cancer patients (stage I-III, 2–4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale ‘fatigue’ of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. Results: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B =

Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistical

Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. Patients and methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherap

Background: Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer. Patients and methods: Patients with metastatic or recurrent endometrial cancer were enrolled. Patients received durvalumab 1500 mg intravenously q4w and olaparib 300 mg 2dd until disease progression, unacceptable toxicity, or patient withdrawal. Patients with at least 4 weeks of treatment were evaluable for analysis. The primary endpoint was progression-free survival at 6 months. Evidence for efficacy was defined as progression-free survival at 6 months in ≥50% of patients. Secondary endpoints included safety, objective response and overall survival. Results: From July 2019, through November 2020, 55 patients were enrolled. At data cut-off (September 2021), 4 of the 50 evaluable patients were still on treatment. Seventeen patients (34%) were progression-free at 6 months. Objective response rate was 16% (95% CI, 8.3 to 28.5) with 1 complete and 7 partial responses. With a median follow-up of 17.6 months, median progression-free survival was 3.4 months (95% CI, 2.8 to 6.2) and median overall survival was 8.0 months (95% CI, 7.5 to 14.3). Grade 3 treatment-related adverse events occurred in 8 patients (16%), predominantly anemia. There were no grade 4 or 5 treatment-related adverse events. Conclusion: The combination of durvalumab and olaparib was well tolerated, but did not meet the prespecified 50% 6-month progression-free survival in this heterogeneous patient population with advanced endometrial cancer.

Background: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2–4 years after diagnosis. Methods: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. Results: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI

Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05). Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.

Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05). Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.

Background: There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up. Methods: SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants. Findings: Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2–24·9) in the olaparib group and 13·9 months (8·0–24·8) in the placebo group; me

Background: There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up. Methods: SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants. Findings: Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2–24·9) in the olaparib group and 13·9 months (8·0–24·8) in the placebo group; me

Background: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. Methods: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0–1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. Findings: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6–69·3) with olaparib and 64·5 months (63·4–68·7) with placebo. Median overall survi

Objectives: In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1. Methods: Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260) or placebo (N = 131), with a 2-year treatment cap in most patients. Safety outcomes were analyzed in detail in randomized patients who received at least one dose of study drug (olaparib, n = 260; placebo, n = 130). Results: Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was <3 months in olaparib-treated patients. The first event of anemia, neutropenia, thrombocytopenia, nausea and vomiting lasted a median of <2 months and the first event of fatigue/asthenia lasted a median of 3.48 months in the olaparib group. These adverse events were manageable with supportive treatment and/or olaparib dose modification in most patients, with few patients requiring discontinuation of olaparib. Of 162 patients still receiving olaparib at month 24, 64.2% were receiving the recommended starting dose of olaparib 300 mg twice daily. Conclusions: Maintenance olaparib had a predictable and manageable adverse event profile in the newly diagnosed setting with no new safety signals identified. Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients.

Background: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. Methods: SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0–1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.go

Purpose: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. Methods: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF < 50% that declined > 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40–50%) and severe cardiotoxicity (LVEF < 40%). Multivariable Cox and mixed model analyses were performed to identify risk factors associated with cardiotoxicity. Additionally, we explored the reversibility of cardiotoxicity in patients who continued trastuzumab. Results: In total, 429 patients were included. Median follow-up for cardiotoxicity was 15 months (interquartile range 8–31 months). The yearly incidence of non-severe + severe cardiotoxicity in the first and second year was 11.7% and 9.1%, respectively, which decreased thereafter. The yearly incidence of severe cardiotoxicity was low (2.8%) and stable over time. In non-smoking patients with baseline LVEF > 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. Conclusions: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment.

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.