Real-life data on treatment and outcomes in advanced ovarian cancer : An observational, multinational cohort study (RESPONSE trial)

Background This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). Methods This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for >= 20 months. Results Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After >= 20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). Conclusions Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. Lay summary Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.Peer reviewe

Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer.

OBJECTIVE:Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. METHODS:Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. RESULTS:In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386). CONCLUSION:In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months

Multivariate, cox analysis of the miRNA prediction score, predicting survival in the clinical cohort (n = 170).

<p>Multivariate, cox analysis of the miRNA prediction score, predicting survival in the clinical cohort (n = 170).</p

Multivariate logistic regression analysis of the miRNA prediction score modelling chemotherapy-resistance (defined as progression/relapse > 6 months, in the clinical cohort (n = 170).

<p>Multivariate logistic regression analysis of the miRNA prediction score modelling chemotherapy-resistance (defined as progression/relapse > 6 months, in the clinical cohort (n = 170).</p

Comparison of miRNAs and chemotherapy response in the current study and the literature.

<p>Comparison of miRNAs and chemotherapy response in the current study and the literature.</p

Baseline characteristics for 170 EOC patients.

<p>Baseline characteristics for 170 EOC patients.</p

Multivariate cox analyses of the miRNA prediction score modelling time to progression from end of last chemotherapy (n = 170).

<p>Multivariate cox analyses of the miRNA prediction score modelling time to progression from end of last chemotherapy (n = 170).</p

List of miRNAs used for prediction of response to chemotherapy.

<p>List of miRNAs used for prediction of response to chemotherapy.</p