What are the initial treatment options for non-small cell lung cancer?

From the Guidelines

The initial treatment options for non-small cell lung cancer (NSCLC) should prioritize molecular testing for driver mutations and PD-L1 expression, with pembrolizumab being a standard first-line option for patients with PS 0-1, tumour PD-L1 ≥50%, and without contraindication for immunotherapy, as recommended by the most recent guidelines 1.

Treatment Approach

The treatment approach for NSCLC depends on the cancer stage, patient's overall health, and specific tumor characteristics.

• For early-stage NSCLC, surgical resection is the preferred treatment.
• For locally advanced disease, a multimodality approach combining chemotherapy, radiation, and sometimes surgery is recommended.
• For advanced or metastatic NSCLC, treatment selection is guided by molecular testing for driver mutations like EGFR, ALK, ROS1, and BRAF, as well as PD-L1 expression.

Molecular Testing and Targeted Therapies

Patients with targetable mutations receive specific tyrosine kinase inhibitors (TKIs) like osimertinib for EGFR mutations or alectinib for ALK rearrangements, as supported by recent guidelines 1.

• EGFR-mutated NSCLC patients should receive first-line EGFR TKIs, including erlotinib, gefitinib, or afatinib.
• Osimertinib is now considered one of the options for patients with sensitising EGFR mutations.

Immunotherapy

Those without targetable mutations but with high PD-L1 expression often receive immunotherapy such as pembrolizumab (200mg IV every 3 weeks) 1.

• Pembrolizumab is considered a standard first-line option for patients with PS 0-1, tumour PD-L1 ≥50%, and without contraindication for immunotherapy.
• Atezolizumab and cemiplimab are alternative options for patients with similar characteristics.

Chemotherapy and Combination Therapies

Patients with low or no PD-L1 expression typically receive chemotherapy plus immunotherapy combinations, as recommended by recent guidelines 1.

• Chemotherapy should be considered for all stage IV NSCLC patients with EGFR- and ALK-negative disease, in the case of a contraindication to immunotherapy, and who are without major comorbidities and PS 0–2.
• Combination of atezolizumab and bevacizumab with carboplatin and paclitaxel should be considered as a therapeutic option in patients with PS 0-1 and metastatic non-squamous NSCLC.

From the FDA Drug Label

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. (1.2) in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of patients with metastatic squamous NSCLC. (1. 2) 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. (1.2. 1)

Las opciones de tratamiento inicial para el cáncer de pulmón de células no pequeñas (NSCLC) son:

• Terapia combinada: pembrolizumab en combinación con pemetrexed y quimioterapia con platino para pacientes con NSCLC metastásico no escamoso sin aberraciones genómicas EGFR o ALK 2.
• Terapia combinada: pembrolizumab en combinación con carboplatino y paclitaxel o paclitaxel unido a proteínas para pacientes con NSCLC metastásico escamoso 2.
• Terapia con un solo agente: pembrolizumab como tratamiento de primera línea para pacientes con NSCLC que expresan PD-L1 (TPS ≥1%) sin aberraciones genómicas EGFR o ALK 2.
• Terapia combinada: ramucirumab en combinación con erlotinib para el tratamiento de primera línea del NSCLC metastásico con deleciones del exón 19 o mutaciones del exón 21 (L858R) de EGFR 3.
• Terapia combinada: ramucirumab en combinación con docetaxel para el tratamiento del NSCLC metastásico con progresión de la enfermedad después de la quimioterapia con platino 3.

From the Research

Initial Treatment Options for Non-Small Cell Lung Cancer

The initial treatment options for non-small cell lung cancer (NSCLC) depend on various factors, including the stage of the disease, the presence of targetable mutations, and the patient's overall health.

• For patients with advanced NSCLC that lacks targetable mutations, platinum-based chemotherapy is a common first-line therapy 4.
• However, for patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice 5.
• The addition of pembrolizumab to chemotherapy has been shown to result in significantly higher rates of response and longer progression-free survival than chemotherapy alone in patients with metastatic nonsquamous NSCLC 4.
• In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel has been shown to result in significantly longer overall survival and progression-free survival than chemotherapy alone 6.
• Other treatment options for NSCLC include anatomical resection and systematic lymph node dissection for early-stage disease, stereotactic body radiotherapy (SBRT) for non-operable patients, and a combination of chemotherapy, radiotherapy, and immunotherapy for locally advanced disease 7.
• Targeted therapies, such as anti-epidermal growth factor receptor (EGFR) therapy and anaplastic lymphoma kinase (ALK) inhibitors, are also available for patients with specific molecular tumor characteristics 8.

Factors Influencing Treatment Choice

The choice of treatment for NSCLC depends on several factors, including:

• The stage of the disease
• The presence of targetable mutations, such as EGFR or ALK mutations
• The level of PD-L1 expression
• The patient's overall health and performance status
• The presence of any comorbidities or contraindications to certain treatments 4, 5, 6, 7, 8.

Emerging Trends and Future Perspectives

Research is ongoing to investigate the efficacy of new treatments, including immunotherapy and targeted therapy, in early-stage NSCLC 7. The development of new target therapies, such as third-generation tyrosine kinase inhibitors (TKIs) and ALK inhibitors, is also an area of active research 8.