What is the treatment approach for a patient with advanced non-small cell lung cancer (NSCLC) of squamous cell carcinoma type, with a large lung mass and involvement of supraclavicular and mediastinal lymph nodes, positive for p40 and p63?

Treatment of Advanced Squamous Cell Non-Small Cell Lung Cancer

For patients with advanced squamous cell NSCLC with supraclavicular and mediastinal lymph node involvement, platinum-based chemotherapy in combination with an anti-PD-(L1) inhibitor is the recommended first-line treatment. 1

Initial Assessment and Staging

• Complete history including smoking history, weight loss, performance status (PS), and physical examination
• Laboratory tests: routine hematology, renal and hepatic function, bone biochemistry
• Contrast-enhanced CT scan of chest and upper abdomen
• PET-CT scan for accurate assessment of mediastinal lymph nodes and distant metastases
• Brain imaging (preferably MRI) for patients eligible for loco-regional treatment
• Bone scan if clinically indicated

Treatment Algorithm for Squamous Cell NSCLC with Lymph Node Involvement

First-Line Treatment Options (PS 0-1):

1. Preferred regimen: Pembrolizumab + carboplatin + (nab)-paclitaxel 1

   • This combination has shown superior survival outcomes compared to chemotherapy alone
   • Treatment typically administered for 4-6 cycles

2. Alternative regimen: Nivolumab + ipilimumab plus two cycles of chemotherapy 1

   • Particularly effective regardless of PD-L1 expression levels

3. For patients with PD-L1 ≥50%:

   • Single-agent pembrolizumab is a standard option 1, 2
   • Alternative options include atezolizumab or cemiplimab

Treatment Considerations Based on Patient Factors:

For PS 2 Patients:

• Single-agent chemotherapy with gemcitabine, vinorelbine, or taxanes 1
• Carboplatin-based combination chemotherapy may be considered in eligible patients 1

For PS 3-4 Patients:

• Best supportive care is recommended 1

For Elderly Patients:

• Carboplatin-based chemotherapy for eligible patients aged 70-89 years with PS 0-2 1
• Single-agent chemotherapy for unfit or comorbid elderly patients 1

Duration of Treatment

• For chemotherapy: 4 cycles recommended, with a maximum of 6 cycles 1
• For immunotherapy: Can be continued for up to 2 years in patients showing response 1
• Treatment should be stopped after no more than 4 cycles in non-responding patients 1

Monitoring and Response Evaluation

• Response evaluation is mandatory after 2-3 cycles of chemotherapy
• Repeat initial radiographic tests that showed tumor lesions
• Consider clinical benefit in certain patient groups

Important Considerations

• P40 and p63 positivity confirm squamous histology but do not currently guide specific targeted therapies
• Unlike non-squamous NSCLC, squamous cell carcinoma rarely harbors EGFR or ALK mutations 3
• Pemetrexed should NOT be used in squamous cell NSCLC 1
• Treatment decisions should be discussed within a multidisciplinary tumor board 1
• Smoking cessation should be highly encouraged as it improves outcomes 1

Second-Line Options

If disease progression occurs after first-line therapy:

• Docetaxel or other single-agent chemotherapy 1
• Immunotherapy if not used in first-line setting

By following this treatment algorithm, patients with advanced squamous cell NSCLC can achieve optimal outcomes in terms of survival and quality of life.