Utility of Adjusting Chemotherapy Dose & Dosing Schedule With the SALVage Weekly Dose-dense Regimen in Patients With Poor Prognostic OVARian Cancers Based on the Tumor Unfavorable Primary Chemosensitivity and Incomplete Debulking Surgery

To demonstrate the superiority in terms of efficacy of a densification of the chemotherapy with the salvage weekly dose-dense carboplatin-paclitaxel regimen compared to the continuation of the standard 3-weekly carboplatin-paclitaxel, in ovarian cancer patients found to have a poor prognostic disease (characterized by a poor chemosensitivity, with an unfavorable KELIMTM score < 1.0, and a disease not amenable to complete interval debulking surgery) after 3 cycles of standard neo-adjuvant chemotherapy.

To demonstrate the superiority in terms of efficacy of a densification of the chemotherapy with the salvage weekly dose-dense carboplatin-paclitaxel regimen compared to the continuation of the standard 3-weekly carboplatin-paclitaxel, in ovarian cancer patients found to have a poor prognostic disease (characterized by a poor chemosensitivity, with an unfavorable KELIMTM score < 1.0, and a disease not amenable to complete interval debulking surgery) after 3 cycles of standard neo-adjuvant chemotherapy.

To compare the efficacy, in term of percentage of patients operated with late complete debulking surgery, between the salvage weekly dose-dense regimen and the standard regimen, regardless of the number of chemotherapy cycles received.

To compare the efficacy of the salvage weekly dose-dense regimen with those of the standard regimen in terms of:

• Radiological response after 3 cycles of treatment, based on the best radiological response using RECIST criteria
• Progression-free survival

To compare the efficacy of the salvage weekly dose-dense regimen with those of the standard regimen in terms of:

• Radiological response after 3 cycles of treatment, based on the best radiological response using RECIST criteria

To assess the impact of the adjustment to the salvage weekly dose-dense regimen on the rate of subsequent prescription of PARP inhibitors (since these drugs are indicated in patients with complete or partial response to platinum-based chemotherapy) in terms of survival.

To assess the impact of the adjustment to the salvage weekly dose-dense regimen on the rate of subsequent prescription of PARP inhibitors (since these drugs are indicated in patients with complete or partial response to platinum-based chemotherapy) in terms of survival.

To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes

To compare the safety profiles of the salvage weekly dose-dense chemotherapy arm with those of the standard 3-weekly carboplatin-paclitaxel with/without bevacizumab, based on the observed adverse-events

To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes

To assess the impact of adding bevacizumab to chemotherapy (salvage or standard arm) on the efficacy outcomes

To compare the quality of life and patient-reported outcomes of the salvage chemotherapy arm with those of the standard regimen

Measure of patient-doctor relationship: The Patient-Doctor Relationship Questionnaire measures patient perceptions of the patient-doctor relationship. Participants rate the level of helpfulness, time, trust, understanding, dedication, agreement, availability, contentment, and accessibility of their healthcare provider. All nine items are rated on a five-point Likert scale from 1 (Not at all appropriate) to 5 (totally appropriate). Mean scores are calculated, and higher scores indicate a better perceived doctor-patient relationship.

Measure of satisfaction with care: One self-generated item developed on the basis of the literature will ask patients in general how they would rate the care they received for their ovarian cancer treatment during the past three months, using a five-point scale from 1 (poor) to 5 (excellent). A higher score reflects a higher satisfaction with their care.

Measure of decision satisfaction: The Satisfaction with Decision scale measures a patient's level of satisfaction with healthcare decisions. It consists of six statements to which respondents are asked to indicate their level of agreement using a five-point scale, from 1 (strongly disagree) to 5 (strongly agree). Total scores are summed, with higher scores indicating greater decisional satisfaction.

To determine the impact of the decision-making process on emotional wellbeing in the short- and medium-term, among patients who have participated in decision-making regarding bevacizumab as a chemosensitizer, late debulking surgery in the case of favorable response to chemotherapy, or PARP inhibitors and/or bevacizumab as maintenance treatment.

Measure of emotional wellbeing: Six self-generated items will be used to measure the concept of eudaimonic or hedonic wellbeing. A 10-point scale from 1 (not at all) to 10 (very much so) will gauge perceptions of feeling hopeful, peaceful, grateful, comforted, connected, and content over the past week, presented as single-word descriptors. Mean scores will be calculated for each subscale, and a mean across all items will be derived to reflect overall emotional wellbeing. Higher scores indicate higher levels of emotional wellbeing.

Measure of treatment beliefs: For patients prescribed PARP inhibitors and/or bevacizumab, four items will be presented to measure treatment beliefs in relation to these treatments. These items are adapted from a Treatment Beliefs Questionnaire originally developed for patients with low back pain, which has been adapted for the current setting with permission. This self-report scale consists of four items assessing perceptions of credibility, effectiveness, concerns, and individual fit of treatment, which are rated on a five-point scale from (1) strongly disagree to (5) strongly agree. Higher scores for each item indicate more positive beliefs about the treatment (with responses on the 'concerns' item being reverse scored).

Measure of treatment (PARPi) adherence: For patients prescribed PARP inhibitors, a three-item scale will be used to measure adherence to PARPi and bevacizumab. Patients will be asked about the number of days in which they missed at least one dose of the treatment (answered numerically), the frequency with which they took their medication in the way they were supposed to over the previous 30 days (rated on a 6-point scale from never to always), and their rating of how 'good a job' they did at taking their medication in the way recommended over the previous 30 days (rated on a 6-point scale from very poor to excellent). Responses will be linearly transformed to a 0-100 scale for analyses, with 0 representing the worst adherence and 100 the best. Summary scores will be calculated as the mean of the three items.

Number of patients with BRCA mutation involved in homologous recombination (%)

Number of patients with BRCA wild-type HRD mutation involved in homologous recombination (%)

Number of patients with BRCA wild-type HRP mutation involved in homologous recombination (%)

Name of tests/assays used in real-life setting

Percentage of tests/assays used in real-life setting (%)

To assess the cost-utility evaluations of the experimental treatment (medico-economic evaluation) in the French context Salvage weekly dose-dense regimen vs the standard regimen, as per randomization Addition of bevacizumab to chemotherapy, as per investigator decision Late debulking surgery after chemotherapy in the case of favorable response to chemotherapy, as per investigator decision Maintenance treatment with bevacizumab with/without PARP inhibitor, or surveillance, as per investigator decision

To assess the cost-effectiveness evaluations of the experimental treatment (medico-economic evaluation) in the French context Salvage weekly dose-dense regimen vs the standard 3-weekly regimen, as per randomization Addition of bevacizumab to chemotherapy, as per investigator decision Late debulking surgery after chemotherapy in the case of favorable response to chemotherapy, as per investigator decision Maintenance treatment with bevacizumab with/without PARP inhibitor, or surveillance, as per investigator decision

A budget impact analysis (BIA) to estimate the financial impact for French Health Insurance of the generalization in the French context of the strategy based on the experimental treatment.