What are the treatment options for non-small cell lung cancer (NSCLC)?

From the Guidelines

Treatment options for non-small cell lung cancer (NSCLC) should be guided by the cancer stage, molecular characteristics, and patient factors, with a focus on improving morbidity, mortality, and quality of life. For early-stage disease (stages I-II), surgical resection is the primary treatment, often followed by adjuvant chemotherapy with platinum-based regimens like cisplatin/carboplatin combined with pemetrexed, vinorelbine, or paclitaxel for 4 cycles, as recommended by the American College of Chest Physicians evidence-based clinical practice guidelines 1. Some key points to consider in the treatment of NSCLC include:

• For locally advanced disease (stage III), a multimodal approach combining chemotherapy, radiation, and possibly surgery is used, with concurrent chemoradiotherapy (cCRT) being the standard curative-intent treatment for patients with unresectable stage III NSCLC 1.
• In stage IV metastatic disease, treatment is guided by molecular testing, with patients with driver mutations receiving targeted therapies such as osimertinib (80mg daily) for EGFR mutations, alectinib (600mg twice daily) for ALK rearrangements, and entrectinib or crizotinib for ROS1 fusions.
• For those without targetable mutations, immunotherapy with pembrolizumab (200mg every 3 weeks), nivolumab, or atezolizumab is standard, either alone or combined with chemotherapy depending on PD-L1 expression.
• Radiation therapy is used for symptom palliation in advanced disease or definitively in earlier stages.
• Treatment selection is based on molecular profiling, which identifies specific genetic alterations that can be targeted with precision therapies, offering better outcomes and fewer side effects than traditional chemotherapy for eligible patients 1. It's worth noting that patient-related and tumor-related factors can influence the balance of risks vs benefits, and patient preferences should also play a significant role in treatment decisions, as highlighted in a review of patients presenting with stage III NSCLC 1. Overall, the treatment of NSCLC requires a comprehensive and multidisciplinary approach, taking into account the latest evidence and guidelines to optimize patient outcomes.

From the FDA Drug Label

KEYTRUDA is indicated:

• in combination with pemetrexed and platinum chemotherapy, as first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations.
• in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of patients with metastatic squamous NSCLC.
• as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is: Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.
• as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. CYRAMZA, in combination with erlotinib, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations CYRAMZA, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy

The treatment options for non-small cell lung cancer (NSCLC) are:

• First-line treatment:
  • Pembrolizumab in combination with pemetrexed and platinum chemotherapy for metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations 2
  • Pembrolizumab in combination with carboplatin and either paclitaxel or paclitaxel protein-bound for metastatic squamous NSCLC 2
  • Pembrolizumab as a single agent for NSCLC expressing PD-L1 (TPS ≥1%) with no EGFR or ALK genomic tumor aberrations, and is Stage III or metastatic 2
  • Ramucirumab in combination with erlotinib for metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations 3
• Second-line treatment:
  • Pembrolizumab as a single agent for metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) with disease progression on or after platinum-containing chemotherapy 2
  • Ramucirumab in combination with docetaxel for metastatic NSCLC with disease progression on or after platinum-based chemotherapy 3

From the Research

Treatment Guidelines for Early and Advanced NSCLC

• For early-stage NSCLC, surgical resection remains the standard of care for functionally operable patients, with the goal of obtaining a complete resection 4.
• Adjuvant chemotherapy with cisplatin and a vinca alkaloid can improve the 5-year survival rate by a few percentage points among patients who undergo surgical resection for NSCLC, but it also increases the risk of serious adverse effects 5.
• For patients with resected stage II or III NSCLC, cisplatin-based adjuvant chemotherapy is the standard of care, but biomarker-informed clinical trials are exploring the use of targeted and immunotherapies to improve outcomes 6.
• Neoadjuvant chemoimmunotherapy with chemotherapy plus nivolumab can be effective in locally advanced stage IIIA NSCLC, with high rates of complete resection and downstaging 7.

Treatment Options for Advanced and Metastatic NSCLC

• There is ongoing uncertainty in comparing surgical and nonsurgical therapies, with or without systemic options, in heterogeneous early-stage NSCLC without lymph node involvement 8.
• Adjuvant targeted therapy (ATKI) and stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (I-SBRT) may be superior approaches for patients with early-stage NSCLC-N0, depending on the genomic mutation status and patient tolerability 8.
• The choice of treatment for advanced and metastatic NSCLC depends on various factors, including the patient's overall health, tumor characteristics, and genetic mutations, and may involve a combination of systemic therapies such as chemotherapy, targeted therapy, and immunotherapy.

Key Considerations

• The role of invasive staging and restaging techniques is currently being debated, but they provide the largest biopsy samples which allow for precise mediastinal staging 4.
• Quality-of-life parameters and surgical quality indicators become increasingly important to determine the short-term and long-term impact of a surgical procedure 4.
• Centralisation of care has been shown to improve results, and evidence-based guidelines should be further developed to provide optimal staging and therapeutic algorithms 4.