GOG 249

Background

Phase III RCT (GOG 249). 601 patients with high-intermediate or high-risk endometrial cancer (HIR: grade 1–2 + deep invasion and/or LVSI, age ≥60; high-risk: grade 3, stage II, clear cell, serous, or carcinosarcoma) after comprehensive surgical staging (TAH-BSO + sentinel or full lymph node evaluation). Randomized to pelvic EBRT (45 Gy) vs vaginal brachytherapy (VBT, 3 × 7 Gy HDR) + 3 cycles carboplatin (AUC 5) + paclitaxel (175 mg/m²). Primary question: can VBT + chemotherapy replace pelvic EBRT for high-risk endometrial cancer?

Interventions and follow up

Arm A: Pelvic EBRT 45 Gy (standard adjuvant RT)
Arm B: VBT (3×7 Gy HDR) + carboplatin AUC 5 + paclitaxel 175 mg/m² × 3 cycle
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: 60 month

Results

60-month RFS: 76% (EBRT) vs 76% (VBT+chemo), HR 0.92 (95% CI 0.69–1.23), P=.58 — equivalent
60-month OS: 87% (EBRT) vs 85% (VBT+chemo), HR 1.04 (95% CI 0.71–1.52), P=.83
Vaginal recurrence: 1% (EBRT) vs 2% (VBT+chemo)
Distant recurrence: 16% (EBRT) vs 14% (VBT+chemo)

Adverse events

Main adverse events: Grade ≥3 hematologic toxicity: 3% (EBRT) vs 63% (VBT+chemo), P<.001. Grade ≥3 non-hematologic: similar. Patient-reported bowel symptoms: worse in EBRT arm during RT; better at 2 years. Neurotoxicity: higher in VBT+chemo arm long-term (chemotherapy effect).

Conclusions

VBT + 3 cycles carboplatin/paclitaxel chemotherapy is equivalent to pelvic EBRT for recurrence-free and overall survival in high-intermediate or high-risk stage I-II endometrial cancer, with the trade-off of higher hematologic toxicity with chemo vs bowel toxicity with EBRT.

Key Limitations

Key Limitations: Included both HIR (low risk of pelvic failure) and true high-risk patients in the same analysis — heterogeneous population. Only 3 cycles of chemotherapy (fewer than the 6 used in GOG 258 or PORTEC-3). Did not include pelvic EBRT + chemotherapy as a third arm — the combination RT+CT regimen was not tested. Predates molecular classification. No OS benefit from chemotherapy addition demonstrated.

Clinical Context

GOG 249 established that for high-intermediate risk endometrial cancer, VBT + chemotherapy and pelvic EBRT are equally effective. In practice, the selection between these approaches is guided by: molecular risk (POLE/MMRd may need less; p53-mutated may need more), histologic risk, and patient preference regarding toxicity profile. PORTEC-3 and GOG 258 address higher-risk (stage III) patients who benefit from combined pelvic RT + chemotherapy.

References

References: Randall ME et al, J Clin Oncol 2019 (GOG 249)