What is the recommended treatment for a patient with adenocarcinoma (a type of non-small cell lung cancer) of the lung, negative Anaplastic Lymphoma Kinase (ALK) and Epidermal Growth Factor Receptor (EGFR), and a positive 10R (right hilar) lymph node?

From the Guidelines

The recommended treatment for a patient with adenocarcinoma of the lung with negative ALK and EGFR mutations and a positive right hilar lymph node (10R) is concurrent chemoradiation therapy, as this approach offers superior survival outcomes despite increased toxicity, based on the most recent and highest quality evidence available 1.

Treatment Approach

This typically consists of platinum-based chemotherapy combined with a second agent, administered concurrently with definitive radiation therapy.

• The chemotherapy regimen may include cisplatin or carboplatin, combined with paclitaxel, pemetrexed, or etoposide.
• Radiation therapy typically delivers 60-66 Gy in 30-33 fractions over 6-7 weeks.

Considerations

• The absence of targetable mutations (ALK and EGFR negative) makes the patient ineligible for targeted therapies, necessitating this standard cytotoxic and immunotherapy approach.
• Prior to initiating treatment, complete staging with PET/CT and brain MRI, pulmonary function testing, and multidisciplinary evaluation are essential to confirm the treatment plan.

Evidence-Based Recommendations

• The treatment strategy should take into account the histology, molecular pathology, age, performance status (PS), comorbidities, and patient’s preferences, as outlined in the guidelines for the management of patients with metastatic non-small-cell lung cancer 1.
• Systemic therapy should be offered to all stage IV patients with PS 0–2, and smoking cessation should be highly encouraged because it improves the outcome 1.

Key Points

• Concurrent chemoradiation therapy is the preferred approach for locally advanced disease (stage III) with positive hilar lymph node involvement.
• The choice of chemotherapy regimen and radiation therapy should be individualized based on patient factors and tumor characteristics.
• Multidisciplinary evaluation and complete staging are essential to confirm the treatment plan and ensure optimal outcomes.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Treatment Options for Adenocarcinoma of the Lung

• The patient has adenocarcinoma of the lung with negative Anaplastic Lymphoma Kinase (ALK) and Epidermal Growth Factor Receptor (EGFR) mutations, and a positive 10R (right hilar) lymph node.
• According to 2, for patients with EGFR/ALK-negative adenocarcinoma, comprehensive genomics can identify other potential targets for therapy, such as KRAS, ERBB2, MET, and RET mutations.
• The study 2 suggests that only 35% of patients with EGFR-negative and EGFR/ALK-negative adenocarcinoma would be recommended for chemotherapy, and the remaining patients may benefit from targeted therapies.

Role of Radiotherapy and Targeted Therapies

• The combination of radiotherapy with targeted agents, such as anti-EGFR, anti-ALK, and anti-angiogenic agents, has been explored in non-small cell lung cancer (NSCLC) 3.
• However, the clinical benefit of combining radiotherapy with targeted agents over standard chemoradiation is still uncertain, and well-designed clinical trials are needed to develop effective combination strategies.
• The use of radiotherapy in oligoprogressive oncogene-driven NSCLC, while continuing first-line targeted therapy, may potentially eradicate resistant cell clones and provide survival benefit 3.

Case Reports and Clinical Experience

• A case report 4 describes a patient with advanced non-smoking lung adenocarcinoma and no EGFR mutation who survived for nearly 12 years after comprehensive therapy with EGFR-TKI-based therapy.
• Another study 5 discusses the personalized treatment of EGFR mutant and ALK-positive patients in NSCLC, highlighting the importance of tyrosine kinase inhibitors (TKIs) in achieving a dramatic therapeutic response.
• However, resistance to TKIs invariably develops, and new therapies are being investigated to overcome this resistance 5.

Potential Treatment Approaches

• Based on the available evidence, potential treatment approaches for the patient may include:

• Comprehensive genomics to identify other potential targets for therapy
• Targeted therapies, such as KRAS, ERBB2, MET, and RET inhibitors
• Combination of radiotherapy with targeted agents
• Chemotherapy, although this may not be the most effective option for all patients 2
• Clinical trials investigating new therapies to overcome resistance to TKIs 5