Table 2.
Statement 7 |
Categorisation by clinical and molecular factors
(Approval 33/33 groups) |
1. Eligibility should be categorised and/or stratified according to: - Histology: high grade serous and high grade endometrioid (with aberrant p53 IHC) vs. others - BRCA1/2 mutation status - Number of prior lines of treatment - Exposure and response to prior treatments - Treatment-free interval from last platinum (TFIp) - Outcome of surgery for recurrent disease 2. Eligibility based only on the interval from last platinum treatment is discouraged. | |
Statement 8 |
Platinum-based regimens as reference arm
(Approval 32/33 groups, 1 opposed*) |
1. Platinum-containing regimens should be the reference arm in patient populations where response to platinum is expected. These include patients with: - Tumours without progression during platinum or shortly following last platinum dose (e.g. within 12 weeks) - Tumours that have responded to the most recent platinum. - No prior platinum therapy - No residual tumour at the start of platinum therapy 2. Appropriate reference arms include: - Platinum-based combination regimens (carboplatin + pegylated liposomal doxorubicin preferred) - PARP inhibitor therapy can be an appropriate alternative reference arm in patients with BRCAm 1/2 who have received >2 prior platinum lines and who are PARPi naive. 3. Maintenance options in the reference arm should be based on study design and prior exposure - PARPi in those who have responded to platinum-based therapy. - Bevacizumab in combination with chemotherapy and as maintenance, including in those who have previously received a PARP inhibitor and/or bevacizumab. 4. Prior exposure to PARPi and/or bevacizumab should be included as stratification factors. Information on duration of exposure and timing of progression (during vs following) should be considered as inclusion or stratification factors. | |
Statement 9 |
Non-platinum regimens as reference arm
(Approval 31/33 groups, 2 opposed*) |
1. Reference arms should contain non-platinum-based regimens when response to platinum is not expected: - Tumours that have progressed on platinum or early (e.g. within 12 weeks) following last platinum dose - Tumours not achieving a response to prior platinum 2. Potential reference arms may include: - Single agent chemotherapy, such as pegylated liposomal doxorubicin (PLD), weekly paclitaxel, gemcitabine, or topotecan - Incorporation of bevacizumab for those receiving PLD, weekly paclitaxel or topotecan. 3. Supportive care (without anti-cancer therapy) can be included as an option in patients who have received >4 treatment lines or where there are no standard of care options. 4. Patients with primary platinum refractory tumours (progressed on or within 12 weeks of first platinum treatment) constitute a specific patient cohort and should be enrolled in dedicated trials, or should be stratified if enrolled in trials for patients not suitable for platinum retreatment. | |
Statement 10 | Biomarker directed trials may allow a broader population based on clinical and molecular factors (Approval 33/33 groups) |
The reference arm of biomarker-driven trials may include both platinum and non-platinum regimens according to patient clinical characteristics, with appropriate stratification. | |
Statement 11 |
Secondary cytoreductive surgery
(Approval 32/33 groups, 1 abstain*) |
1. Secondary cytoreduction is permitted prior to clinical trial enrolment and should be included as a stratification factor pre-randomisation, along with extent of residual disease. 2. Secondary cytoreduction should be considered in all patients with recurrent disease fulfilling criteria predictive of successful complete resection 3. Secondary cytoreduction as a component of protocol-directed management (post randomisation) would only be permitted if included within the trial design. - When included as a component of protocol-directed therapy, secondary cytoreduction should be reserved for patients selected using a validated score (e.g. AGO score) |