4
Indication details
- Combined Agent(s)
- Carboplatin and paclitaxel
- Control Arm
- Placebo + carboplatin + paclitaxel
- Therapeutic Indication
- Dostarlimab with carboplatin and paclitaxel for the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability high (MSI H) primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy.
- Tumour Type
-
Gynaecological Malignancies
- Tumour Sub-type
- Endometrial Cancer
- Tumour Stage
- Primary advanced or recurrent
- Tumour Sub-Group
- dMMR/MSI-H
- Trial Name
- RUBY
- NCT Number
- NCT03981796
- Trial Phase
- Phase III
Approval details
- FDA Approval
- FDA approval July 2023
- EMA Approval
- EMA (CHMP) October 2023 EC decision December 2023
- Comment
- Approval based on the dMMR-MSI-H population. This overall survival benefit may be exaggerated by inadequate post progression therapy in the control arm since for the dMMR/MSI-H population only 41.5% of patients in the control arm received subsequent immunotherapy
Primary Outcome(s)
- Primary Outcome(s)
- PFS. OS was an exploratory endpoint
- Evaluated Outcome
- PFS
- Form(s)
- Form 2b
Outcome Data
- PFS Control
- 7 months (estimated from Kaplan-Meier)
- PFS Gain
- 18 months (estimated gain based on PE HR 0.28)
- PFS HR
- 0.28 (0.16-0.50)
- OS Control
- 31.4 months
- OS Gain
- 66.7 months (estimated gain based on HR 0.32)
- OS HR
- For DMMR-MSIH subpopulation, HR 0.32 (0.17-0.63), nominal P=0.0002; indicating a benefit in OS as dramatic as in PFS (40% OS maturity)
Adjustments
- QoL Comment
-
No QoL benefit
- Toxicity Comment
-
In the overall population, >10% of patients discontinued treatment due to AEs (19.1% in dostarlimab vs 8.1% in placebo).
However, since no such information is available for the DMMR-MSI-H subgroup, it is not eligible for dowgrade due to incremental toxicity
Score (after adjustments)
- Preliminary non-curative score
-
3
- Long-term plateau in the PFS curve
- 1+
- Non-curative score
-
4
Scorecard details
- ESMO-MCBS version
- ESMO-MCBS v1.1
- Scorecard ID
- 396
- Scorecard version
- 1
- Issue date
- 22.09.2023
- Last update
- 09.10.2024
Legend
Information about symbols, abbrevations and color codes
Red = negative
Green = positive
Grey = neutral
?
Grey + ? = neutral with pending data
- DFS
- Disease-Free Survival
- DoR
- Duration of Response
- EFS
- Event-Free Survival
- HR
- Hazard Ratio
- NEB
- No evaluable benefit
- NI
- Non-inferiority Study
- ORR
- Overall Response Rate
- OS
- Overall Surival
- pCR
- Pathological Complete Response/Remission
- PFS
- Progression-Free Survival
- QoL
- Quality of Life
- RFS
- Relapse-Free Survival
- RR
- Response Rate
QoL adjustments
Other adjustments*
Serious and disabling adverse effects
Red = negative / deterioration
Green = positive / improvement
QoL adjustments
Red = negative / deterioration
Green = positive / improvement
Other adjustments*
Red = negative / deterioration
Green = positive / improvement
Serious and disabling adverse effects
Red = negative / deterioration
Green = positive / improvement
* Other adjustments include:
- Long-term plateau in the survival curve
- Long-term plateau in the PFS curve
- Early stopping or crossover
- Only improved PFS mature data shows no OS advantage and no improved Qol.