Abstract
BackgroundLung immune prognostic index (LIPI) refers to a biomarker combining derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). Its prognostic effect on advanced small cell lung cancer (SCLC) patients receiving programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors plus chemotherapy as first-line treatment remains unclear. Our research investigated the relationship between pretreatment LIPI and the prognosis of patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy.MethodsAdvanced SCLC patients receiving PD-1/PD-L1 inhibitors plus chemotherapy as first-line treatment from Jan 2015 to Oct 2020 were included. Based on the values of dNLR and LDH, the study population was divided into two groups: LIPI good and LIPI intermediate/poor. The Kaplan-Meier method was used to compute the median survival time and the log-rank test was used to compare the two groups. Univariate and multivariate analyses were used to examine the correlation between the pretreatment LIPI and clinical outcomes.ResultsOne hundred patients were included in this study, of which, 64% were LIPI good (dNLR < 4.0 and LDH < 283 U/L), 11% were LIPI poor (dNLR ≥ 4.0 and LDH ≥ 283 U/L), and the remaining 25% were LIPI intermediate. The LIPI good group had better progression-free survival (PFS) (median: 8.4 vs 4.7 months, p = 0.02) and overall survival (OS) (median: 23.8 vs 13.3 months, p = 0.0006) than the LIPI intermediate/poor group. Multivariate analysis showed that pretreatment LIPI intermediate/poor was an independent risk factor for OS (HR: 2.34; 95%CI, 1.13, 4.86; p = 0.02). Subgroup analysis showed that pretreatment LIPI good was associated with better PFS and OS in males, extensive disease (ED), PD-1 inhibitor treatment, smokers, and liver metastasis (p < 0.05).ConclusionsPretreatment LIPI could serve as a prognostic biomarker for advanced SCLC patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy.
Highlights
Small-cell lung cancer (SCLC) constitutes 13 - 15% of total lung cancer cases, and is characterized by rapid progression and early distant metastasis [1, 2]
A meta analysis study found that both progressive disease (PD)-L1 inhibitors and PD1 inhibitors plus chemotherapy as first-line treatment could provide a significant improvement of survival time compared with chemotherapy alone for advanced SCLC patients [12]
The results showed that PD-L1 inhibitors (HR: 2.37; 95%confidence interval (CI), 1.10, 5.11; p = 0.03), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 (HR: 6.96; 95%CI, 2.25, 21.55; p = 0.001), liver metastasis (HR: 2.66; 95%CI, 1.19, 5.93; p = 0.02), bone metastasis (HR: 4.61; 95%CI, 2.01, 10.59; p < 0.001), and Lung immune prognostic index (LIPI) intermediate/poor (HR: 2.34; 95%CI, 1.13, 4.86; p = 0.02) were independent risk factors for overall survival (OS) (Table 4)
Summary
Small-cell lung cancer (SCLC) constitutes 13 - 15% of total lung cancer cases, and is characterized by rapid progression and early distant metastasis [1, 2]. The phase II EA5161 study has demonstrated the addition of nivolumab at first-line treatment significantly improved the progression-free survival (PFS) and OS of ES-SCLC patients (median PFS: 5.5 vs 4.6 months, p = 0.012; median OS: 11.3 vs 8.5 months, p = 0.038) [10]. The phase III KEYNOTE-604 study showed that advanced SCLC patients receiving first-line pembrolizumab plus chemotherapy had better OS compared with those receiving chemotherapy alone, but the difference did not meet the predefined statistical threshold [11]. A meta analysis study found that both PD-L1 inhibitors and PD1 inhibitors plus chemotherapy as first-line treatment could provide a significant improvement of survival time compared with chemotherapy alone for advanced SCLC patients [12]. Its prognostic effect on advanced small cell lung cancer (SCLC) patients receiving programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors plus chemotherapy as first-line treatment remains unclear. Our research investigated the relationship between pretreatment LIPI and the prognosis of patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy
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