Background
Pooled analysis of two phase III RCTs: NSGO-9501/EORTC-55991 (n=382, Nordic/European) and MaNGO ILIADE-III (n=79, Italian). Both enrolled high-risk early endometrial cancer (stage IC grade 3, IIA grade 3, IIB, or IIIA any grade) after surgery and randomized to pelvic RT alone vs sequential chemotherapy followed by pelvic RT (or RT followed by chemotherapy in MaNGO). This pooled analysis examined whether adding chemotherapy to adjuvant RT improves outcomes over RT alone in high-risk stage I-III endometrial cancer.
Interventions and follow up
Arm A: Pelvic RT (46–50 Gy) alone
Arm B: Sequential chemotherapy (platinum/anthracycline-based, 4–6 cycles) then pelvic RT (or RT then chemotherapy)
Primary endpoint: PFS (pooled analysis)
mFollow up: 6.2 year
Arm B: Sequential chemotherapy (platinum/anthracycline-based, 4–6 cycles) then pelvic RT (or RT then chemotherapy)
Primary endpoint: PFS (pooled analysis)
mFollow up: 6.2 year
Results
5-year PFS: 75.4% (RT alone) vs 82.0% (CT+RT), HR 0.63 (95% CI 0.44–0.89), P=.009
5-year OS: 79.1% (RT alone) vs 83.7% (CT+RT), HR 0.69 (95% CI 0.46–1.03), P=.07 — trend toward benefit
Recurrence (distant): Lower in CT+RT arm; pelvic recurrence similar
5-year OS: 79.1% (RT alone) vs 83.7% (CT+RT), HR 0.69 (95% CI 0.46–1.03), P=.07 — trend toward benefit
Recurrence (distant): Lower in CT+RT arm; pelvic recurrence similar
Adverse events
Main adverse events: Chemotherapy added significant hematologic toxicity and GI toxicity vs RT alone. Completion rates for sequential CT+RT approximately 75–80%.
Conclusions
Sequential chemotherapy + RT significantly improved PFS over RT alone in high-risk endometrial cancer (HR 0.63), with a non-significant trend toward OS benefit (HR 0.69), supporting the hypothesis that combining chemotherapy with RT improves outcomes — which was tested definitively in PORTEC-3.
Key Limitations
Key Limitations: Pooled analysis of two trials with different chemotherapy regimens and treatment sequencing — heterogeneity limits interpretation. Not powered for OS. Sequential (not concurrent) chemotherapy was used — PORTEC-3 tested concurrent cisplatin + RT. Both trials used older platinum/anthracycline regimens, not carboplatin + paclitaxel. Patient populations and RT doses varied between trials.
Clinical Context
The NSGO/EORTC/MaNGO pooled analysis provided the hypothesis-generating evidence for PORTEC-3. These results established that chemotherapy adds value to RT for high-risk endometrial cancer. PORTEC-3 subsequently tested concurrent cisplatin + RT followed by carboplatin + paclitaxel maintenance vs RT alone in a properly powered RCT, confirming improved failure-free survival — particularly for stage III and serous/p53-mutated tumors.
References