Olaparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation: SOLO1 China cohort.

PURPOSE: Maintenance therapy with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib provided a substantial progression-free survival (PFS) benefit compared with placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (BRCAm) who were in clinical complete or partial response following platinum-based chemotherapy in the Phase III SOLO1 global study. This led to the approval of maintenance olaparib in China, USA, EU, Japan and other countries, in the newly diagnosed setting. This separate China cohort of the SOLO1 study investigated the efficacy and safety of maintenance olaparib within the Chinese population. PATIENTS AND METHODS: In this double-blind, multicentre study, patients were randomized 2:1 to receive oral olaparib tablets (300 mg twice daily) or placebo. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). RESULTS: Of the 64 randomized patients, 44 received olaparib and 20 placebo. Olaparib reduced the risk of disease progression or death by 54% compared with placebo (HR 0.46, 95% Cl 0.23-0.97; median PFS was not reached in the olaparib arm vs 9.3 months in the placebo arm). The most common AEs in the olaparib arm were nausea (63.6 vs 25.0% with placebo), anaemia (59.1 vs 15.0%) and leukopenia (54.5 vs 20.0%). Grade ≥3 AEs were experienced by 56.8% of olaparib patients and 30.0% of placebo patients. CONCLUSIONS: Results in the SOLO1 China cohort support the use of olaparib as maintenance treatment for Chinese patients with newly diagnosed advanced ovarian cancer who have a BRCAm and are in complete or partial response after platinum-based chemotherapy.

Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.

PURPOSE: To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer. RESULTS: We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events). CONCLUSIONS: PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.

The association between neuropsychological impairment, self-perceived cognitive deficit, symptoms, and health related quality of life in newly diagnosed ovarian cancer patients.

Objective: To assess cognitive function in patients newly diagnosed with ovarian cancer (OC) before treatment and explore the relationship between neuropsychological impairment, self-perceived cognitive deficit, symptoms, and health-related quality of life in them. Methods: From May 2021 to February 2022, 105 women newly diagnosed with OC were enrolled in the Cancer Center of Fudan University, Shanghai, China. Objective and subjective cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) scale and Perceptual Deficits Questionnaire (PDQ). Symptoms and quality of life were evaluated using the Memorial Symptom Assessment Scale (MSAS) and Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O), respectively. Results: This study included 105 newly diagnosed OC patients, with an average age of 49.73 (±8.48) years. Of these, 72.38% had impaired neuropsychological test scores, especially in delayed recall, abstraction, and visuospatial/executive function. Retrospective, and prospective memory were the most serious perceived deficits. The results of the MoCA test were not associated with PDQ (Rs = -0.180, P = 0.067) and significantly correlated with the distress index, physiological and total scores of the MSAS, and emotional well- being of the FACT-O. The PDQ positively correlated with all MSAS dimensions but not with the FACT-O. Conclusion: The incidence of neuropsychological impairment in patients newly diagnosed with OC was high, with no association with self-perceived cognitive deficits. It is recommended that healthcare providers include cognitive impairment in symptom management in this population, who may benefit from early assessment, prevention, and intervention.

Anti-Angiogenesis Maintenance Therapy in Newly Diagnosed and Relapsed Ovarian Cancer: A Meta-analysis of Phase III Randomized Controlled Trials.

Aim: Anti-angiogenesis agents have been added as maintenance therapy in ovarian cancer over the past decade. The aim of this meta-analysis was to analyze the efficacy of anti-angiogenesis therapy in newly diagnosed and relapsed ovarian cancer. Methods: PubMed, Embase, and Cochrane databases were searched for all phase III randomized controlled trials (RCTs) that assessed the efficacy and toxicity of anti-angiogenesis agents in ovarian cancer. Overall survival (OS) and progression-free survival (PFS) were used to evaluate the effectiveness of anti-angiogenesis therapy in ovarian cancer. Results: A total of 6097 patients with newly diagnosed ovarian cancer from 5 phase III RCTs and 2943 patients with relapsed ovarian cancer from 6 phase III RCTs were included in this meta-analysis. The pooled results showed that anti-angiogenesis maintenance therapy significantly improved PFS (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.76-0.93; p = 0.001), but not OS (HR, 0.98; 95% CI, 0.91-1.05; p = 0.49) compared with placebo in patients with newly diagnosed ovarian cancer. In patients with relapsed ovarian cancer, the pooled results showed a significant improvement on OS (HR, 0.89; 95% CI, 0.82-0.98; p = 0.02) and PFS (HR, 0.61; 95% CI, 0.52-0.72; p < 0.001). The pooled results also showed that the anti-angiogenesis agents were associated with an increase in the occurrence of severe hypertension, neutropenia, diarrhea, thrombocytopenia, headache, and bleeding in ovarian cancer. However, infrequent fatal adverse events occurred in the anti-angiogenesis groups. Conclusions: Study results suggest that anti-angiogenesis agents were an effective therapy for newly diagnosed and relapsed ovarian cancer, especially for relapsed ovarian cancer. Anti-angiogenesis agents may be associated with some severe but not fatal adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021283647.

First-Line Treatment with Olaparib for Early Stage BRCA-Positive Ovarian Cancer: May It Be Possible? Hypothesis Potentially Generating a Line of Research.

Olaparib is currently approved in maintenance treatment of advanced ovarian cancer after response to first-line chemotherapy for breast related cancer antigens (BRCA) mutated patients. The use of this agent is based on data from SOLO1 study that observed a decreased risk of disease progression or death and a median progression-free survival about 36 months longer in case of therapy with olaparib. However, this trial recruited only patients with advanced stage ovarian cancer. The aim of this review is to retrace the available data in order to clarify the potential efficacy and feasibility of olaparib administration in newly diagnosed epithelial ovarian cancer also in early stages.