Oligoprogression (OPD) of non-small-cell lung cancer (NSCLC) occurs in approximately half of patients under targeted compounds (TKI) and facilitates use of regional therapies that can prolong survival. In order to characterize OPD in immunotherapy (IO)-treated NSCLC, we analyzed the failure pattern under PD-1/PD-L1 inhibitors (n = 297) or chemoimmunotherapy (n = 75). Under IO monotherapy, OPD was more frequent (20% vs. 10%, p < 0.05), occurred later (median 11 vs. 5 months, p < 0.01), affected fewer sites (mean 1.1 vs. 1.5, p < 0.05), and involved fewer lesions (1.4 vs. 2.3, p < 0.05) in the first compared to later lines. Lymph nodes (42%, mainly mediastinal) and the brain (39%) were mostly affected, followed by the lung (24%) and other organs. Compared to multifocal progression, OPD occurred later (11 vs. 4 months, p < 0.001) and was associated with longer survival (26 vs. 13 months, p < 0.001) and higher tumor PD-L1 expression (p < 0.001). Chemoimmunotherapy showed a similar incidence of OPD as IO monotherapy (13% vs. 11% at 2 years). Local treatments were applied regularly for brain but only in 50% for extracranial lesions. Thus, NSCLC oligoprogression is less common under IO than under TKI, but also favorable. Since its frequency drops later in the disease, regular restaging and multidisciplinary evaluation are essential in order to exploit the full therapeutic potential.
Background: The advanced lung cancer inflammation index [ALI: body mass index  serum albumin/neutrophil-tolymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). Patients and methods: This retrospective study included 672 stage IV NSCLC patients treated with programmed deathligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. Results: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) ¼ 0.402, P < 0.0001, n ¼ 460], but not chemo-immunotherapy (HR ¼ 0.624, P ¼ 0.111, n ¼ 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P ¼ 0.008) and time-on-treatment (HR ¼ 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR ¼ 0.694, P ¼ 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor
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