What are the treatment approaches for non-small cell lung cancer (NSCLC) across all stages?

From the Guidelines

Treatment approaches for non-small cell lung cancer (NSCLC) should prioritize surgical resection for early-stage disease, multimodality approaches for locally advanced disease, and targeted therapies or immunotherapies for metastatic disease, considering patient performance status, comorbidities, and preferences to optimize morbidity, mortality, and quality of life outcomes. For early-stage disease (stages I-II), surgical resection is the primary treatment, typically involving lobectomy with lymph node sampling, as recommended by 1 and 1. Adjuvant chemotherapy with platinum-based regimens like cisplatin/vinorelbine for 4 cycles may be added for stage II and some high-risk stage IB patients, as suggested by 1 and 1. Stereotactic body radiation therapy (SBRT) is an option for medically inoperable early-stage patients, as indicated by 1 and 1. For locally advanced disease (stage III), a multimodality approach is used, combining chemotherapy (cisplatin/etoposide) with radiation therapy, followed by immunotherapy (durvalumab) for unresectable cases, although specific guidelines for this stage are not directly provided in the given evidence. In stage IV metastatic disease, treatment is guided by molecular testing, with patients having driver mutations receiving targeted therapies: osimertinib for EGFR mutations, alectinib or brigatinib for ALK rearrangements, and crizotinib for ROS1 alterations, as outlined in 1 and 1. For those without targetable mutations, immunotherapy (pembrolizumab, nivolumab, atezolizumab) is used, either alone for high PD-L1 expression or combined with chemotherapy, as recommended by 1. Platinum-based chemotherapy combinations remain important for patients without high PD-L1 expression or when immunotherapy is contraindicated, as noted in 1 and 1. Treatment selection considers the patient's performance status, comorbidities, and preferences, with supportive care integrated throughout all stages to manage symptoms and improve quality of life, emphasizing the importance of a multidisciplinary approach as suggested by 1, 1, and 1.

Some key points to consider in the treatment of NSCLC include:

• The role of surgical resection in early-stage disease
• The use of adjuvant chemotherapy in stage II and high-risk stage IB disease
• The application of SBRT for medically inoperable patients
• The importance of molecular testing in guiding treatment for metastatic disease
• The use of targeted therapies for patients with driver mutations
• The role of immunotherapy in patients without targetable mutations
• The integration of supportive care to manage symptoms and improve quality of life

Given the complexity and the stage-specific nature of NSCLC treatment, it is crucial to prioritize the most recent and highest quality evidence, such as 1, which provides comprehensive guidelines for the management of metastatic NSCLC, emphasizing personalized treatment approaches based on molecular characteristics and patient factors.

From the FDA Drug Label

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated: Non-Small Cell Lung Cancer (NSCLC) 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. for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. as a single agent, for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

The treatment approaches for non-small cell lung cancer (NSCLC) across all stages include:

• Combination therapy: pembrolizumab in combination with pemetrexed and platinum chemotherapy, or carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment for metastatic NSCLC.
• Single agent therapy: pembrolizumab as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1, or for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 with disease progression on or after platinum-containing chemotherapy.
• Neoadjuvant and adjuvant treatment: pembrolizumab in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery, for resectable NSCLC.
• Adjuvant treatment: pembrolizumab as a single agent, for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB, II, or IIIA NSCLC. Additionally, gemcitabine is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer (NSCLC) 2, 3.

From the Research

Treatment Approaches for Non-Small Cell Lung Cancer (NSCLC)

The treatment of NSCLC varies according to the stage of the disease. Here are the treatment approaches for NSCLC across all stages:

• For early-stage NSCLC (stage 1), surgical resection via lobectomy is the treatment of choice, with the goal of complete anatomic resection of the tumor and mediastinal lymph node evaluation 4.
• For patients with early-stage NSCLC who cannot undergo surgery due to comorbidities or patient preference, stereotactic ablative radiotherapy (SABR) is an alternative option 4.
• Adjuvant cisplatin-based chemotherapy is the standard of care for completely resected high-risk stage IB and stage II NSCLC 4.
• For locally advanced NSCLC (stage 3), the treatment is stratified according to resectability. Patients with resectable disease may require additional treatments such as chemotherapy and radiation, while patients with unresectable disease will require definitive chemoradiation therapy with adjuvant durvalumab 5.
• For patients with limited metastatic disease (stage 4), the combination of SBRT and systemic therapy is beneficial 5.
• Targeted therapies, such as KRAS-directed therapies, EGFR inhibitors, and ALK inhibitors, have changed the treatment landscape of NSCLC and led to improved patient survival across all stages of lung cancer 6.
• Chemotherapy, such as paclitaxel, is also used in the treatment of NSCLC, particularly in combination with platinum compounds 7.

Treatment Options by Stage

Here are the treatment options for NSCLC by stage:

• Stage 1: Surgery, SABR, adjuvant chemotherapy
• Stage 2: Surgery, adjuvant chemotherapy
• Stage 3: Surgery, chemotherapy, radiation, chemoradiation therapy
• Stage 4: Systemic therapy, targeted therapy, SBRT

Emerging Therapies

Emerging therapies, such as immunotherapy and molecularly targeted therapy, are being developed and tested for the treatment of NSCLC 8, 6. These therapies have shown promise in improving patient outcomes and are expected to play a larger role in the treatment of NSCLC in the future.