What does the research say about using chemotherapy versus immunotherapy for advanced Non-Small Cell Lung Cancer?

For advanced non-small cell lung cancer (NSCLC), the choice between chemotherapy and immunotherapy depends on tumor characteristics like PD-L1 expression and genetic mutations. In general, immunotherapy (such as PD-1/PD-L1 inhibitors) has become a standard first-line treatment for patients with high PD-L1 levels (≥50%), while chemotherapy is still used alone or in combination with immunotherapy. Research shows that immunotherapy can improve survival, but not all patients benefit equally.

What the research says

A real-world meta-analysis of pembrolizumab monotherapy in advanced NSCLC with PD-L1 ≥50% found a pooled mean overall survival of 21.0 months and a 60-month survival rate of 29%, with any-grade adverse events in 52% of patients ⁸. This supports pembrolizumab as a standard first-line option for this subgroup. For patients with lower PD-L1 or without targetable mutations, chemotherapy combined with immunotherapy (neoadjuvant immunochemotherapy) has shown promise. A meta-analysis of neoadjuvant anti-PD-1/PD-L1 plus chemotherapy in resectable NSCLC reported high resection and pathological response rates, though it focused on earlier-stage disease ⁴. In advanced NSCLC, sequential therapy may be considered: a case report described a patient with MET exon 14 skipping mutation and high PD-L1 who received a PD-1 inhibitor followed by a MET inhibitor, achieving disease control ³. Additionally, the timing of immunotherapy administration may matter: a meta-analysis found that early time-of-day immune checkpoint inhibitor administration was associated with improved overall survival in advanced solid tumors, including NSCLC ⁶. For patients with EGFR mutations, targeted therapy (e.g., lazertinib plus amivantamab) is preferred over immunotherapy, as PD-1 inhibitors are less effective in EGFR-mutant NSCLC ⁵. Overall, the evidence indicates that immunotherapy is a powerful tool for advanced NSCLC, especially in PD-L1 high tumors, but chemotherapy remains important, and combining or sequencing treatments can be beneficial.

What to ask your doctor

• What is my tumor's PD-L1 expression level, and does it make me a good candidate for immunotherapy?
• Do I have any genetic mutations (like EGFR or MET) that would affect whether immunotherapy or targeted therapy is best for me?
• Would combining chemotherapy with immunotherapy be more effective than either alone for my stage of cancer?
• Are there any data on the best time of day to receive immunotherapy infusions to improve outcomes?
• What are the possible side effects of immunotherapy compared to chemotherapy, and how are they managed?