Evolving Strategies for Treating Advanced NSCLC in Elderly Patients: The Role of PD-1/PD-L1 Inhibitors

Managing advanced non-small cell lung cancer in patients over 70 presents a therapeutic paradox: how to harness immunotherapy’s power without tipping the balance toward intolerable toxicity.

Oncologists face mounting evidence that elderly NSCLC treatment requires greater nuance than younger cohorts. Performance status declines and polypharmacy often preclude aggressive regimens, yet PD-1 inhibitors remain the most promising immunotherapy for durable responses. The question becomes how to reconcile efficacy and safety when considering monotherapy versus combination therapy with PD-1 inhibitors or PD-L1 inhibitors.

A recent real-world study and nomogram for survival prognosis highlights that PD-1/PD-L1 inhibitor monotherapy delivers significant survival gains in elderly patients with advanced NSCLC, especially those with minimal comorbidities. However, the study's retrospective design and specific selection criteria may limit the generalizability of these findings. In the referenced study, the median overall survival for patients with ECOG 0–1 was 18.5 months (95% CI: 16.2–20.8), based on a cohort of 150 patients.

Specifically, the incidence of grade ≥3 adverse events increased from 15% with monotherapy to 35% with combination therapy, while median overall survival remained similar at approximately 12 months in both groups. These earlier findings suggest that adding agents beyond PD-1 inhibitors amplifies toxicity and hospitalizations, eroding the potential quality-of-life gains that immunotherapy alone can offer.

Prognostic factors such as baseline performance status, neutrophil-to-lymphocyte ratio (NLR), and tumor PD-L1 expression emerge as critical for tailoring treatment. NLR is a measure of systemic inflammation calculated by dividing the number of neutrophils by the number of lymphocytes in the blood, while PD-L1 expression refers to the presence of the programmed death-ligand 1 protein on tumor cells, which can predict response to certain immunotherapies. Biomarkers inform risk stratification, identifying those elderly patients most likely to derive meaningful benefit from monotherapy protocols. Personalized oncology treatment decisions increasingly hinge on these real-world parameters.

Consider an 82-year-old patient with high PD-L1 tumor proportion score (TPS) and preserved performance status: monotherapy with a PD-L1 inhibitor achieved durable disease control while avoiding cytopenias and neuropathy associated with platinum-based combinations. This illustrative case mirrors outcomes modeled by the nomogram, which integrates clinical variables to project survival probabilities at six, twelve and eighteen months.

Incorporating a nomogram for prognosis into tumor board discussions offers a structured approach to estimate individualized survival and weigh trade-offs between efficacy and toxicity. Such a tool enhances shared decision-making, guiding physicians and patients through complex immunotherapy choices.

Optimizing treatment regimens for advanced NSCLC in the elderly thus demands reassessment of combination strategies and greater reliance on predictive scoring systems. As immunotherapy indications expand, sharpening patient selection through biomarkers and prognostic models will be vital to improving outcomes without compromising safety.

Key Takeaways:

• Monotherapy with PD-1/PD-L1 inhibitors presents a favorable benefit–risk balance for elderly NSCLC patients.
• Combination therapy increases adverse events without clear survival benefits in this demographic.
• Prognostic factors, including performance status and biomarker expression, guide personalized immunotherapy decisions.
• Nomograms enhance the precision of survival predictions and treatment planning.