Senthil Kumar: First-Line Treatment in Advanced Endometrial Carcinoma

Senthil Kumar, Medical Oncologist at Red Hills Chennai, shared a post on X:

“First-Line Treatment in Advanced Endometrial Carcinoma

Disease Overview

Median Age at Diagnosis: 60–65 years
Metastatic at Presentation: 5–15% 

Common Metastatic Sites:

Lungs: 40%
Lymph Nodes: 30%
Liver: 20%
Bones: 10% 

Median Overall Survival (OS): 12–18 months
Median Progression-Free Survival (PFS): 5–6 months 

Histological and Molecular Profiling

Histological Subtypes (WHO Classification):

Endometrioid Adenocarcinoma (Grade 1–3)
Serous Carcinoma
Clear Cell Carcinoma
Carcinosarcoma (MMMT)
Undifferentiated/Dedifferentiated Carcinoma

Essential Molecular Testing:

Mismatch Repair (MMR) IHC: MLH1, PMS2, MSH2, MSH6
Microsatellite Instability (MSI) Testing
Estrogen Receptor (ER) & Progesterone Receptor (PR) Status
HER2 Testing (IHC/FISH): Serous/Carcinosarcoma tumors
PD-L1 IHC (Optional)
p53 IHC (Optional)
POLE Mutation Testing (Optional)

First-Line Systemic Therapy Options

Chemotherapy-Based Regimens:

1. Carboplatin + Paclitaxel (CP) – GOG-209 Trial

Comparison: CP vs. TAP (Paclitaxel, Doxorubicin, Cisplatin)
Outcome: CP was non-inferior to TAP
Median PFS (Carbo + Pacli): 13 months
Median OS (Carbo + Pacli): 37 months
Standard of Care for advanced/recurrent endometrial cancer 

2. Carboplatin + Paclitaxel + Bevacizumab (GOG-86P)

Median PFS: 13 months (not significant)
Median OS: 34 months (significant) 

3. Carboplatin + Paclitaxel + Pembrolizumab (NRG-GY018)

PFS HR (dMMR): 0.3
PFS HR (pMMR): 0.54
Median PFS (pMMR): 13 months
Median OS (pMMR): 28 months
Maintenance: Pembrolizumab every 6 weeks for 2 years 

4. Dostarlimab + Carboplatin/Paclitaxel (RUBY/ENGOT-EN6/GOG3031)

PFS HR (dMMR): 0.3
PFS HR (pMMR): 0.8
Overall OS HR: 0.69 (significant)
Maintenance: Dostarlimab for 3 years 

5. Carboplatin + Paclitaxel + Trastuzumab (HER2-positive)

Median PFS: 13 months
Median OS: 24 months 

6. Durvalumab + Chemotherapy ± Olaparib (DUO-E Trial)

PFS HR (Durvalumab): 0.71
PFS HR (Durvalumab + Olaparib): 0.55
Median PFS (Durvalumab): 10.0 months
OS HR (dMMR): 0.4 

7. Atezolizumab + Chemotherapy (AtTEnd Trial)

Median PFS: 10 months
Median OS: 38 months 

Surgical Cytoreduction

Stage IVB Intra-abdominal Disease:

Complete Cytoreduction (CRS): Median OS = 48 months

Optimal Cytoreduction (OCR, <1 cm residual): Median OS = 24 months

Neoadjuvant chemotherapy (NACT) considered if OCR is feasible.

Note: Data is retrospective 

Hormonal Therapy

Indicated for:

• Low-grade, indolent, endometrioid histology
• Hormone receptor-positive (HR+) tumors
• Low-volume disease, especially in elderly/frail patients 

Key Trial Data (GOG-119):

Regimen: Daily Tamoxifen (40mg )+ alternate weekly MPA ( 200mg)
ORR: 27%
Median PFS: 2.7 months
Median OS: 14 months 

Other Hormonal Agents:

Progestins: Medroxyprogesterone acetate, Megestrol acetate
Aromatase Inhibitors: Letrozole, Anastrozole
Tamoxifen (Selective Estrogen Receptor Modulator)
Fulvestrant (Estrogen Receptor Degrader)

Final Insights

Optimized Treatment Approach

1. dMMR/MSI-H Tumors:

Preferred: Chemotherapy + Immunotherapy (Pembrolizumab/Dostarlimab/Durvalumab/Atezolizumab)
Benefit: Significant OS and PFS improvement

2. pMMR/MSS Tumors:

Preferred: Chemotherapy (CP) ± Immunotherapy (PFS benefit only) 

3. HER2-Positive Tumors:

Preferred: Chemotherapy + Trastuzumab 

4. Low-Volume, HR-Positive Tumors:

Preferred: Hormonal Therapy (Letrozole, Megestrol, Tamoxifen) 

5. Surgical option in intra abdominal mets (Stage IVB):

Preferred: Cytoreduction (if feasible) with NACT consideration.”