Immune Checkpoint Inhibition Plus Chemotherapy Did Not Improve Survival Among Older Patients With Advanced Non-Small Cell Lung Cancer

According to findings from a retrospective cohort study, immune checkpoint inhibition plus chemotherapy did not significantly improve overall survival (OS) or progression-free survival (PFS) compared to immune checkpoint inhibition alone among older patients with previously untreated, advanced non-small cell lung cancer (NSCLC). 

“[Immune checkpoint inhibition plus] chemotherapy is now a standard treatment for NSCLC without targetable oncogene alterations, but there are few data on [immune checkpoint inhibition plus] chemotherapy for patients 75 years and older,” stated Yoko Tsukita, MD, PhD, T ohoku University Graduate School of Medicine, Sendai, Japan, and coauthors. This study aimed “to inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of [immune checkpoint inhibition plus] chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC.” 

In this study, 1245 patients with postoperative or radiotherapy-recurrent NSCLC between 75 and 95 years were enrolled to receive first-line systemic therapy with either an immune checkpoint inhibitor plus chemotherapy (n = 354), an immune checkpoint inhibitor alone (n = 425), platinum-doublet chemotherapy (n = 311), or single-agent chemotherapy (n = 155). Patients treated in the first-line setting with molecular targeted drugs were excluded. Patients had PD-L1 expression < 1% (n = 268), PD-L1 expression 1% to 49% (n = 387), PD-L1 expression ≥50% (n = 410), or PD-L1 of unknown expression (n = 180). Primary end points included OS, PFS, and safety. 

At analysis, median OS was 20 months in the immune checkpoint inhibition plus chemotherapy arm, 19.8 months in the immune checkpoint inhibition alone arm, 12.8 months in the platinum-doublet chemotherapy arm, and 9.5 months in the single-agent chemotherapy arm. After propensity score matching, there were no differences found in OS and PFS regardless of the addition of chemotherapy. For patients with PD-L1 expression < 1%, median OS hazard ratio (HR) was 0.98 and the PFS HR was 0.92 (95% confidence interval [CI], 0.67-1.42; P = .90). Statistical significance was not reached for patients with PD-L1 expression 1% to 49% or PD-L1 expression ≥50%. Grade ≥ 3 immune-related adverse events occurred in 86 patients in the immune checkpoint inhibition plus chemotherapy arm and 76 patients in the ICI alone arm (P = .03).

“In this study, [immune checkpoint inhibitor plus] chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older,” concluded Dr Tsukita et al. “Based on these results, [immune checkpoint inhibition] alone may be recommended for older adult patients with PD-L1–positive NSCLC.”

Source: 

Tsukita Y, Tozuka T, Kushiro K, et al. Immunotherapy or chemoimmunotherapy in older adults with advanced non–small cell lung cancer. JAMA Oncol. Published online: March 7, 2024. doi:10.1001/jamaoncol.2023.6277