Senthil Kumar: First-Line Therapy for Advanced/Metastatic Penile Cancer

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

“First-Line Therapy for Advanced/Metastatic Penile Cancer

Patient Selection

1. Performance Status (PS):

PS 0-1 (Fit Patients):

Eligible for aggressive regimens like TIP or TPF.

PS ≥2:

Use less intensive regimens such as carboplatin-based combinations or single agents like paclitaxel.

2. Molecular Biomarkers and Tumor Characteristics:

HPV-Positive Tumors:

Associated with improved outcomes and higher response rates to immune checkpoint inhibitors (ICI).

TMB-High (≥10 mut/Mb): Enriched responses with ICIs; TMB-high tumors represent ~15% of cases.

PD-L1 Expression: Biomarker for ICI use, particularly in refractory settings.

3. Organ Function and Comorbidities:

Renal Dysfunction:

Avoid cisplatin; prefer carboplatin.

Frailty or Severe Toxicity Risk:

Favor single-agent therapies or investigational regimens.

First-Line Systemic Therapy

1. TIP (Paclitaxel, Ifosfamide, Cisplatin)

Indication:

• Gold standard for fit patients with metastatic PSCC.

Efficacy:

• Overall Response Rate (ORR): ~50%.
• Complete Response (CR): ~10–13%.
• Median Progression-Free Survival (PFS): ~6–7 months.
• Median Overall Survival (OS): ~12–17 months.

Adverse Effects:

Significant toxicities:

• Myelosuppression, nephrotoxicity, neurotoxicity.

2. Cisplatin + 5-FU

Indication:

• Alternative for patients unable to tolerate triplet regimens.

Efficacy:

• ORR: ~30–38%.
• Median PFS: ~5 months.
• Median OS: ~8 months.

Toxicity:

• High incidence of mucositis and renal toxicity;

3. Carboplatin + Paclitaxel

Indication: Preferred for patients with renal dysfunction or PS ≥2.

Efficacy:

• ORR: ~20–40%.
• Median OS: ~6–8 months.

Toxicity:

• Lower nephrotoxicity but risks of neuropathy and myelosuppression.

4. Pembrolizumab + Platinum-Based Chemotherapy

Evidence (HERCULES Trial):

Combination of pembrolizumab + 5-FU + cisplatin in 33 patients:

• ORR: 39% (CR: 1 patient; PR: 12 patients).
• Median PFS: 5.4 months.
• Median OS: 9.6 months.

Responses enriched in:

• TMB-High: ORR ~75%.
• HPV-Positive: ORR ~55.6%.

Indication:

• Emerging biomarker-driven strategy for first-line therapy in advanced PSCC.

Emerging Therapies

1. EGFR Inhibitors (Cetuximab, Panitumumab):

Investigational use in EGFR-overexpressing tumors; responses reported in small retrospective studies.

2. Single-Agent Immunotherapy:

Atezolizumab ± Radiation (PERICLES Study):

• ORR: 17% (7% CR, 10% PR).
• Median OS: ~11.5 months.
• Improved outcomes in HPV-positive tumors and T-cell-enriched microenvironments.

Retifanlimab (ORPHEUS Trial):

• ORR: 17%.
• Median PFS: 2 months.
• Median OS: 7.2 months.

3. Cabozantinib + Nivolumab ± Ipilimumab:

Partial responses in ~45% of patients (N=9) in phase I/II trials.

Clinical Insights

Optimal First-Line Regimens:

TIP:

High response rates and survival benefit in fit patients.

Cisplatin + 5-FU:

Effective alternative for patients with moderate PS.

Carboplatin-Based Regimens:

For frail patients or those with renal dysfunction.

Immunotherapy:

Promising in biomarker-selected patients (PD-L1-positive, HPV-positive, TMB-high).

Patient-Centric Therapy:

Fit Patients:

Aggressive combination therapies (TIP, pembrolizumab + chemotherapy).

Frail or Comorbid Patients:

Carboplatin + paclitaxel or single-agent paclitaxel.”

More posts featuring Senthil Kumar.