What is the prognosis for a patient with stage 4 non-small cell lung cancer (NSCLC)?

From the Guidelines

The prognosis for Stage 4 non-small cell lung cancer (NSCLC) is generally poor, with a 5-year survival rate of approximately 6% when patients receive historic cytotoxic chemotherapy regimens, but certain patients with metastatic NSCLC who are eligible for newer targeted therapies or immunotherapies are now surviving longer, with 5-year survival rates ranging from 15% to 50%, depending on the biomarker 1. At this advanced stage, cancer has spread from the lungs to distant organs such as the brain, bones, liver, or adrenal glands. Treatment typically focuses on extending life and improving quality of life rather than cure. Standard treatment approaches include systemic therapies like chemotherapy (often platinum-based combinations such as carboplatin/paclitaxel or cisplatin/pemetrexed), immunotherapy (pembrolizumab, nivolumab, atezolizumab), targeted therapies for specific genetic mutations (osimertinib for EGFR mutations, alectinib for ALK rearrangements, crizotinib for ROS1 mutations), and palliative radiation. Some key considerations in the management of Stage 4 NSCLC include:

• The importance of a multidisciplinary approach to care, including discussion of treatment options within a tumor board 1
• The role of palliative care in improving quality of life, with studies showing benefits in terms of symptom management, mood, and even overall survival 1
• The need for individualized treatment planning, taking into account factors such as performance status, extent of metastases, and specific genetic mutations present in the tumor
• The potential for targeted therapies and immunotherapies to significantly improve outcomes in patients with certain biomarkers Survival can vary significantly based on several factors including the patient's performance status, extent of metastases, specific genetic mutations present in the tumor, response to treatment, age, and comorbidities. Patients with certain driver mutations who receive appropriate targeted therapies may experience significantly longer survival than the average. Supportive care including pain management, nutritional support, and treatment of symptoms is essential throughout the disease course to maintain quality of life. Early integration of palliative care into standard oncologic care has been shown to improve quality of life, reduce symptoms, and even improve overall survival in patients with Stage 4 NSCLC 1.

From the FDA Drug Label

The median OS was 12.3 months vs. 10.3 months [HR 0.80 (95% CI: 0.68,0.94), final p-value of 0.013, stratified log-rank test]. The trial demonstrated a statistically significant improvement in OS for patients (PD-L1 TPS ≥50%, TPS ≥20%, TPS ≥1%) randomized to KEYTRUDA as compared with chemotherapy. Median OS was 16.7 (13.9,19.7) months for the pembrolizumab group and 12.1 (11.3,13.3) months in the chemotherapy group, with an HR of 0.81 (95% CI: 0.71,0.93) for TPS ≥1%

The prognosis for Stage 4 non small cell lung cancer is generally poor, but treatment with pembrolizumab or bevacizumab can improve overall survival (OS).

• The median OS for patients with TPS ≥1% was 16.7 months with pembrolizumab and 12.1 months with chemotherapy.
• The hazard ratio (HR) for OS was 0.81 (95% CI: 0.71,0.93) for TPS ≥1% and 0.80 (95% CI: 0.68,0.94) for bevacizumab with paclitaxel and carboplatin.
• Pembrolizumab and bevacizumab can be used as first-line treatment for patients with non-squamous NSCLC.
• The efficacy of these treatments may vary depending on patient characteristics, such as age, sex, and weight loss 2, 3.

From the Research

Stage 4 Non-Small Cell Lung Cancer Prognosis

• The prognosis for stage 4 non-small cell lung cancer (NSCLC) remains poor, with treatment focusing on improving quality of life and extending survival 4.
• Platinum-based doublets are a standard of care for patients with good performance status, although the addition of a third cytotoxic agent or most targeted/biological agents does not improve survival, except for bevacizumab in certain cases 4.
• For patients with poor performance status, pembrolizumab alone or in combination with low-dose chemotherapy may be considered, with some studies suggesting improved long-term survival compared to historical outcomes with platinum-based chemotherapy 5.

Treatment Options

• Pembrolizumab plus chemotherapy has been shown to significantly prolong overall survival in patients with metastatic, squamous NSCLC, with a median overall survival of 15.9 months compared to 11.3 months with placebo-combination therapy 6.
• The addition of pembrolizumab to chemotherapy has also been found to increase progression-free survival, with a median of 6.4 months compared to 4.8 months with chemotherapy alone 6.
• Platinum-based chemotherapy may increase PD-L1 expression on tumor cells, potentially affecting treatment outcomes and predicting poor clinical response 7.

Survival Outcomes

• Median overall survival for patients with stage 4 NSCLC treated with pembrolizumab or pembrolizumab plus chemotherapy has been reported to range from 12.5 months to 20.4 months 8.
• Patients with poor performance status may have shorter survival outcomes, although pembrolizumab-based therapies have shown improved long-term survival compared to historical controls 5.
• Overall survival benefits have been consistent regardless of PD-L1 expression levels, with some studies suggesting improved outcomes for patients with high PD-L1 expression 8, 6.