Two major real-world studies provide compelling evidence that immune checkpoint inhibitors (ICIs) deliver significant clinical benefits for non-small cell lung cancer (NSCLC) patients with poor performance status, a population traditionally excluded from clinical trials and facing limited treatment options.
Poor Performance Status Patients Show Survival Benefit
A comprehensive analysis of 1,395 NSCLC patients with ECOG performance status (PS) ≥2 from the Flatiron Health database revealed that ICI treatment provides substantial survival advantages compared to no treatment, regardless of PD-L1 expression levels. The study addressed a critical knowledge gap, as patients with PS ≥2 have historically been excluded from randomized controlled trials due to concerns about treatment tolerability and efficacy.
For patients with high PD-L1 expression (≥50%), pembrolizumab monotherapy demonstrated a median overall survival of 7.1 months compared to 2.7 months for patients receiving no documented treatment. After propensity score adjustment, the hazard ratio for death was 0.39 (95% CI: 0.32-0.47), representing a 61% reduction in mortality risk.
In the low PD-L1 expression cohort (<50%), both pembrolizumab monotherapy and combination pembrolizumab plus chemotherapy showed significant survival benefits compared to no treatment, with adjusted hazard ratios of 0.55 (95% CI: 0.41-0.70) and 0.39 (95% CI: 0.32-0.46), respectively.
Monotherapy Comparable to Combination Therapy in Poor PS Patients
A particularly noteworthy finding emerged when comparing treatment approaches in patients with low PD-L1 expression and poor performance status. The study found no statistically significant difference in overall survival (adjusted HR = 0.80, 95% CI: 0.53-1.10) or progression-free survival (adjusted HR = 0.99, 95% CI: 0.64-1.37) between pembrolizumab monotherapy and pembrolizumab plus chemotherapy.
The median survival times were 5.6 months for pembrolizumab monotherapy versus 7.9 months for combination therapy, while median progression-free survival was nearly identical at 7.7 months and 7.9 months, respectively. This suggests that for poor PS patients, ICI monotherapy may offer similar efficacy with potentially reduced toxicity burden.
Chinese Real-World Data Confirms ICI Efficacy Across Different Agents
Complementing these findings, a Chinese real-world study of 351 NSCLC patients treated with various ICIs between 2018-2021 found consistent efficacy across different PD-1 inhibitors. The overall cohort achieved a median progression-free survival of 9.5 months with an objective response rate of 47.3%.
The study compared five different ICIs: pembrolizumab (65.2% of patients), nivolumab (5.1%), camrelizumab (6.0%), tislelizumab (6.8%), and sintilimab (7.7%). Despite variations in median PFS ranging from 6.8 to 10.4 months and ORR from 45.0% to 54.2%, no statistically significant differences were observed between the various agents (P = 0.942).
In a subgroup analysis of stage IV patients with ECOG PS 0-1 receiving first-line ICI treatment, the median PFS was 10.6 months with an ORR of 51.5%, closely matching results from clinical trials of first-line ICI combinations.
Safety Profile Remains Manageable
The Chinese study documented immune-related adverse events (irAEs) requiring glucocorticoid intervention in 17.1% of patients, with 9.7% experiencing grade 3 or higher events. The most common serious irAE was checkpoint inhibitor pneumonitis, occurring in 11.1% of patients overall and 4.8% at grade 3 or above.
Importantly, patients who developed mild irAEs (grade 1-2) showed significantly better survival outcomes than those without irAEs, with median PFS of 17.4 months versus 8.7 months, supporting the concept that mild immune activation may serve as a positive prognostic indicator.
Clinical Implications for Treatment Decisions
These real-world findings have important implications for clinical practice. The data suggest that ECOG PS ≥2 should not automatically exclude NSCLC patients from ICI consideration, as the survival benefit appears substantial even in this challenging population.
For patients with high PD-L1 expression and poor PS, pembrolizumab monotherapy emerges as a clear treatment option. For those with low PD-L1 expression, the similar outcomes between monotherapy and combination therapy suggest that treatment decisions can be individualized based on patient tolerance and comorbidities.
The consistency of efficacy across different PD-1 inhibitors in the Chinese cohort also provides reassurance that treatment decisions can be guided by factors such as availability, cost, and patient preference rather than concerns about differential efficacy between agents.
These real-world studies collectively demonstrate that ICIs represent a valuable treatment option for NSCLC patients with poor performance status, a population with historically limited therapeutic options and poor prognosis.
