Senthil Kumar: First-Line Systemic Treatment for Advanced/Metastatic Salivary Gland Tumors

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

“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.
• Tumour 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).”