📊 First-Line Systemic Treatment for Advanced/Metastatic Salivary Gland Tumors
---
📉 Disease Overview
Incidence: Rare malignancies (~5% of head and neck cancers) 🧬
Prognosis: Highly variable depending on histology and molecular profile 🔬
Factors Impacting Survival:
Patient Factors:
Age 👴,
performance status (PS) 🏋️,
comorbidities ❤️
Disease Factors:
Histology 🧬,
Tumor burden ⚖️,
Disease tempo (indolent 🐢 vs. rapidly progressive 🚀),
Symptomatic 🤕 vs. asymptomatic 😌,
Molecular alterations 🧪
---
💉 Molecular Alterations and Targeted Therapy Options
Molecular Alterations to be Tested:
NTRK Fusions → Larotrectinib, Entrectinib (First-line) 🎯
HER2 Amplification/Overexpression → Trastuzumab + Taxane/Carboplatin-Paclitaxel ± Pertuzumab (First-line) 💉, T-DM1, Trastuzumab Deruxtecan (Subsequent lines) 🔄
Androgen Receptor (AR)
Expression → Chemotherapy (First-line) 💉, ADT (Bicalutamide + GnRH analogs) or Enzalutamide (Subsequent lines)
RET Mutations → Selpercatinib, Pralsetinib (First-line) 🔬
BRAF Mutations → Dabrafenib + Trametinib (First-line)
MSI-High/dMMR Tumors → Immunotherapy (Pembrolizumab, Nivolumab) (Second-line) 💉🛡️
📌 Note: Tumor NGS profiling 🧬 may be done for all patients due to the rarity and genetic heterogeneity of salivary gland tumors.
---
💉 Chemotherapy Regimens
First-Line Chemotherapy Options:
Combination Regimens:
CAP: Cyclophosphamide + Doxorubicin (or Epirubicin) + Cisplatin
Cisplatin + 5-FU
Cisplatin + Gemcitabine
Cisplatin + Vinorelbine
Carboplatin + Paclitaxel
Cisplatin + Docetaxel
Single Agents:
Vinorelbine
Mitoxantrone
Cisplatin
Gemcitabine
Paclitaxel (Note: Ineffective in ACC)
Doxorubicin (or Epirubicin)
Methotrexate
Special Consideration for SDC:
HER2-Positive: Trastuzumab + Taxane/Carboplatin-Paclitaxel ± Pertuzumab 💉🧬
AR-Positive: Chemotherapy (First-line) → ADT (Bicalutamide + GnRH analogs) (Subsequent lines) 🔄
---
🎯 Special Considerations for Adenoid Cystic Carcinoma (ACC)
Oligometastatic Disease:
Local ablative therapies (surgery, SBRT, ablative radiation) may be employed 🔥
Polymetastatic Indolent Disease:
Observation is an option for asymptomatic, stable disease 😌
Polymetastatic Progressive Symptomatic Disease:
If disease shows ≥20% increase over the preceding 6 months or in case of organ dysfunction , initiate chemotherapy as first-line treatment
Surgical Options:
Lung metastasectomy 🩻 for oligometastatic disease with Disease-Free Interval (DFI) >3 years
Second-Line Therapy:
TKIs like Lenvatinib, Sorafenib, Axitinib
---
📝 Final Insights
1. NTRK Fusion-Positive Tumors:
First-line:
Larotrectinib or Entrectinib 🎯 due to high response rates and low toxicity
2. HER2-Positive Tumors:
First-line:
Trastuzumab + Taxane/Carboplatin-Paclitaxel ± Pertuzumab 💉
Subsequent Lines:
T-DM1, Trastuzumab Deruxtecan 🔄
3. AR-Positive, HER2-Negative Tumors:
First-line:
Platinum-based Chemotherapy 💉
Subsequent Lines:
ADT (Bicalutamide + GnRH analogs) or Enzalutamide
4. RET and BRAF Mutations:
First-line:
Selpercatinib, Pralsetinib (RET)
First-line:
Dabrafenib + Trametinib (BRAF)
5. ACC:
Observation 😌 for asymptomatic, indolent disease 🐢
Local Ablative Therapy 🔥 for oligometastatic disease
Systemic therapy 💉 for symptomatic/progressive disease 🚀
Lung Metastasectomy 🩻 for oligomets, DFI >3 years
6. MSI-High/dMMR Tumors:
Subsequent lines:
Pembrolizumab or Nivolumab 💉🛡️
7. Clinical Trials:
Strongly encouraged 📚 due to limited standard treatment options
8. General Approach for SGC:
Systemic therapy 💉 preferred for rapidly progressive 🚀 or symptomatic 🤕 disease
Molecular profiling 🧬 is critical for treatment decisions
Oligometastatic disease: Consider local therapies (surgery 🏥, ablative therapies 🔥, radiotherapy ⚡)
---