Senthil Kumar: Systemic Treatment for Advanced/Metastatic Synovial Sarcoma
Senthil Kumar, Medical Oncologist at Red Hills Chennai, shared a post on X:
“Systemic Treatment for Advanced/Metastatic Synovial Sarcoma.
Disease Overview
Age at Diagnosis: Typically 35–40 years
Metastatic at Presentation: ~10% of cases
Common Sites of Metastasis:
- Lungs (80%)
- Lymph Nodes (7–20%)
- Bones (2–5%)
Median Overall Survival (OS): 15–17 months
Median Progression-Free Survival (PFS): 6 months
Molecular Characteristics
Pathognomonic Translocation: t(X;18)(p11.2;q11.2) in >95% of cases
Fusion Genes: SYT (Chromosome 18) + SSX (Chromosome X) → SS18-SSX1, SS18-SSX2, SS18-SSX4
Detection Methods: FISH or RT-PCR
Emerging Molecular Targets: MAGE-A4, NY-ESO-1, EZH2
Chemotherapy Options
First-Line Chemotherapy:
Single-Agent Doxorubicin
- ORR: ~22%
- Median OS: 12–15 months
- Median PFS: ~5 months
Doxorubicin + Ifosfamide Combination
- ORR: ~60%
- Median OS: 12–15 months
- Median PFS: ~7 months
Subsequent-Line Chemotherapy:
Ifosfamide / High-Dose Ifosfamide
- Median OS: ~12 months
- Median PFS: ~4–6 months
Pazopanib
- Median OS: ~12 months
- Median PFS: ~4–6 months
Trabectedin
- Median OS: ~14 months
- Median PFS: ~3 months
Docetaxel + Gemcitabine
- Median OS: ~8 months
- Median PFS: ~3 months
Targeted Therapy Options
Regorafenib: Median PFS: 5.6 months
Pazopanib:
- Median PFS: 4–6 months
- Median OS: 12.5 months
Tazemetostat (EZH2 Inhibitor): Stable disease in some patients
FDA-Approved Therapy
Tecelra / Afami-cel (Afamitresgene Autoleucel)
- Gene therapy for MAGE-A4 positive, HLA-A*02 patients
- Median PFS: 7 months
Emerging Therapy: Lete-cel
For HLA-A*02:01, *02:05, *02:06-positive patients with NY-ESO-1–expressing (≥30% staining at 2+/3+ per IHC) metastatic or unresectable synovial sarcoma.
Interesting Trials and Insights
SARC028 Trial (Pembrolizumab in Sarcomas): ORR: ~10% (1 out of 10 cases of synovial sarcoma responded)
CMB305 Trial (NY-ESO-1 Vaccine + Atezolizumab): No PFS or OS benefit
IGNYTE-ESO Trial (Lete-cel):
- ORR: 41%
- Median Duration of Response (DoR): 18 months
- Complete Response (CR): In 3 cases
- Adverse Events: Cytopenia (due to lymphodepletion), Cytokine Release Syndrome (CRS): 90%, Grade 3 in 12%
SPEARHEAD-1 Trial (Afami-cel):
- ORR: 37%
- DoR: 6 months
REGOSARC Trial (Regorafenib in STS): Median PFS: 5.6 months
ImmunoSarc Trial (Sunitinib + Nivolumab): Median PFS: 5.9 months
Final Insights
Preferred First-Line Treatment: Doxorubicin with/without Ifosfamide
Next Best Options:
- Docetaxel + Gemcitabine
- Trabectedin
- Pazopanib
- Ifosfamide / High-Dose Ifosfamide
- Regorafenib
- T-cell Therapies
Immunotherapy (Investigational):
Emerging Therapies:
- Tecelra / Afami-cel (Afamitresgene Autoleucel): Approved for MAGE-A4 positive, HLA-A*02 patients
- Lete-cel: For HLA-A*02:01, *02:05, *02:06-positive patients with NY-ESO-1–expressing metastatic or unresectable synovial sarcoma
Clinical Trials: Strongly recommended for access to novel treatments
Oligometastatic Disease Management
Resectable Oligometastatic Lung Disease: Lung Metastasectomy improves survival in selected patients
Non-Surgical Oligometastatic Disease:
- Ablative therapies (e.g., radiofrequency ablation)
- Stereotactic Body Radiotherapy (SBRT).”
More posts featuring Senthil Kumar.
-
ESMO 2024 Congress
September 13-17, 2024
-
ASCO Annual Meeting
May 30 - June 4, 2024
-
Yvonne Award 2024
May 31, 2024
-
OncoThon 2024, Online
Feb. 15, 2024
-
Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023