Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer

The ORR was defined as the percentage of patients with objective response (complete response \[CR\] or partial response \[PR\]) according to RECIST 1.1 and was assessed by ICR. Only patients whose CR/PR response was confirmed by a second scan at least 4 weeks after the initial response, with no evidence of progression between the initial and CR/PR confirmation visit were included. CR: Disappearance of all target lesions (TLs) and non-TLs (NTLS) since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 millimeters (mm). PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters. Data obtained up until progression, or last evaluable assessment in the absence of progression were included in the assessment of ORR.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Population: The evaluable for response (EFR) analysis set included all patients who received at least 1 dose of IP and had measurable disease at baseline according to the independent review of baseline imaging data. RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

The EORTC QLQ-OV28 is specific for ovarian cancer and consists of 28 items assessing abdominal/gastrointestinal symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items) and 4 other single items. Each scale was scored from 0 to 100 with higher scores on the symptom scales indicating greater symptom burden. The best observed change from baseline is presented for each EORTC QLQ-OV28 scale, where a 10-point change in the score was used to identify patients who improved, stayed the same or deteriorated. The number of patients with a best observed change from baseline response of improved, stayed the same, or deteriorated in the EORTC QLQ-OV28 is presented.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). EORTC QLQ-OV28 assessments were performed at baseline and every 8 weeks relative to first dose until discontinuation of IPs.

Population: The FAS included all patients who received at least 1 dose of either of the IPs. Only patients with non-missing baseline and post-baseline data were included in the analysis.

The EORTC QLQ-C30 questionnaire assesses health-related quality of life (HRQoL). The questions are grouped into a global health status/QoL scale, 5 functional scales (physical, role, emotional, cognitive and social), 3 multi-item symptom scales (fatigue, pain, nausea/ vomiting), 5 single items assessing cancer symptoms (dyspnea, loss of appetite, insomnia, constipation, diarrhea), and 1 item on the financial impact of the disease. Each scale/item is scored from 0 to 100. Higher scores on the global health status/QoL scale and functional scales indicate better health status/function. Higher scores on the symptom scales/items indicate a greater symptom burden. A 10-point change in the score was used to identify patients who improved, stayed the same or deteriorated from baseline. The number of patients with a best observed change from baseline response of improved, stayed the same or deteriorated for each EORTC QLQ-C30 scale/item is presented.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). EORTC QLQ-C30 assessments were performed at baseline and every 8 weeks relative to first dose until discontinuation of IPs.

Population: The FAS included all patients who received at least 1 dose of either of the IPs. Only patients with non-missing baseline and post-baseline data were included in the analysis.

The DCR was defined as the percentage of patients who had a best overall response of CR, PR or Stable Disease (SD) at 6 months. CR: Disappearance of all TLs and NTLs since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters. SD: Neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase to qualify for progressive disease (PD) (at least a 20% increase in the sum of diameters of TLs with an absolute increase of at least 5 mm and progression of existing NTLs). Patients had to have demonstrated SD for at least 23 weeks following the start of treatment. The Investigator assessment was based on the FAS and the ICR used the EFR analysis set. The percentage of patients with disease control for each assessment is presented.

Time frame: From baseline up to 6 months after first doses of IPs. RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Population: The EFR set included all patients who received at least 1 dose of IP and had measurable disease at baseline according to the independent review of baseline imaging data. The FAS included all patients who received at least 1 dose of either of the IPs.

DoR was defined as the time from date of first documented response (which was subsequently confirmed) until date of documented progression or death in the absence of disease progression (i.e. date of progression free survival \[PFS\] event or censoring - date of first response + 1). The end of response coincided with the date of progression or death from any cause used for the PFS endpoint. The time of initial response was defined as the latest of the dates used towards the first visit that was CR or PR that was subsequently confirmed. If a patient did not progress following a response, the PFS censoring time was used. The Investigator assessment was based on the FAS and the ICR used the EFR analysis set. The median DoR for each assessment is presented and was calculated using the Kaplan-Meier technique.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Population: The EFR set included all patients who received at least 1 dose of IP and had measurable disease at baseline according to the independent review of baseline imaging data. The FAS included all patients who received at least 1 dose of either of the IPs.

OS was defined as the time from the date of first dose of IP until death due to any cause regardless of whether the patient withdrew from treatment or received another anti-cancer therapy (i.e. date of death or censoring - date of first dose + 1). Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. The median OS was calculated using the Kaplan-Meier technique.

Time frame: From baseline until death due to any cause, assessed until primary analysis DCO (8 months after last patient received their first dose of IPs).

Population: The FAS included all patients who received at least 1 dose of either of the IPs.

PFS was defined as the time from date of first dose of IP until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from treatment or received another anti-cancer therapy prior to progression (i.e. date of PFS event or censoring - date of first dose + 1). Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. The median PFS, calculated using the Kaplan-Meier technique, is presented for the ICR and the Investigator assessment, both based on the FAS.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Population: The FAS included all patients who received at least 1 dose of either of the IPs.

The median time to discontinuation of IPs or death was defined as the time from the date of first dose of IP to the earlier of the date of discontinuation of both IPs, or death date. If 1 IP was discontinued before the other, the TDT reflected the time from the date of first dose to the earliest IP discontinuation date. The median TDT was calculated using the Kaplan-Meier technique.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs).

Population: The FAS included all patients who received at least 1 dose of either of the IPs.

The percentage of patients with a response (CR/PR), including patients with both confirmed and unconfirmed responses, based on investigator assessed RECIST 1.1 data is presented. Confirmed responses included patients whose CR/PR response was confirmed by a second scan at least 4 weeks after the initial response, with no evidence of progression between the initial and CR/PR confirmation visit. CR: Disappearance of all TLs and NTLs since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters.

Time frame: From baseline to primary analysis DCO (8 months after last patient received their first dose of IPs). RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Population: The FAS included all patients who received at least 1 dose of either of the IPs.