PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

Ran Zeng, Fang Liu, Chen Fang, Jin Yang, Lifeng Luo, Ping Yue, Beili Gao, Yuchao Dong, Yi Xiang, Ran Zeng, Fang Liu, Chen Fang, Jin Yang, Lifeng Luo, Ping Yue, Beili Gao, Yuchao Dong, Yi Xiang

Abstract

Objectives: The objective of this study is to evaluate whether PIV (Pan-Immune-Inflammation Value) and PILE [a score derived from PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)] can predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in patients with extensive-stage (ES) small cell lung cancer (SCLC).

Methods: A total of 53 patients with ES-SCLC in the control group of clinical trial (NCT03041311) were included in this study. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE scores were composited based on PIV, LDH levels, and ECOG PS. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. Moreover, the predictive ability of PIV and PILE was validated in an independent real-world group consisting of 84 patients.

Results: Patients in the low PIV group (PIV < median) had longer progression-free survival (PFS) and overall survival (OS) than those in the high PIV group (PIV ≥ median), along with the HR, which was 2.157 and 2.359, respectively (PFS HR 95% CI: 1.181-3.940, p = 0.012; OS HR 95% CI: 1.168-4.762, p = 0.020). High PILE score was observed relating to worse treatment efficacy (disease control rate (DCR): 84.21% vs. 100%, p = 0.047; durable clinical benefit (DCB) rate: 10% vs. 48.5%, p = 0.060) and poor clinical outcome (median PFS: 4.75 vs. 5.53 m, p = 0.043; median OS: 7.13 vs. 15.93 m, p = 0.002). Similar results were obtained about the predictive and prognostic abilities of PIV and PILE scores in the validation group.

Conclusions: High PIV and high PILE were correlated with worse clinical outcomes in ES-SCLC patients treated with anti-PD-1/PD-L1 inhibitor combined with chemotherapy, reflecting that PIV and PILE might be useful to identify patients unlikely to benefit from anti-PD-1/PD-L1 therapy.

Keywords: PILE; Pan-Immune-Inflammation Value; anti-PD-1/PD-L1 inhibitors; biomarker; small cell lung cancer.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Zeng, Liu, Fang, Yang, Luo, Yue, Gao, Dong and Xiang.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for PFS (A) and OS (B) according to baseline PIV in clinical trial group. Yellow lines indicate patients with low PIV (<581.95), and blue lines indicate patients with high PIV (≥581.95). mOS, median overall survival; mPFS, median progression-free survival; m, month; PIV, Pan-Immune-Inflammation Value.
Figure 2
Figure 2
Kaplan–Meier curves for PFS (A) and OS (B) according to baseline PILE in clinical trial group. Yellow lines indicate patients with low PILE (PLIE score = 0, 1); blue lines indicate patients with high PILE (PLIE score = 2, 3). mOS, median overall survival; mPFS, median progression-free survival; m, month.
Figure 3
Figure 3
The relations between PILE and clinical efficacy of immunotherapy. (A) Overall best response in low and high PILE groups. (B) DCB and NDB patients in low and high PILE groups. (C) DOR for patients in low PILE group and high PILE groups. CR, complete response; PR, partial response; SD, stable disease; PD, progression disease; ORR, objective response rate; DCR, disease control rate; DOR, duration of response; DCB, durable clinical benefit; NDB, non-durable clinical benefit.
Figure 4
Figure 4
Kaplan–Meier curves for PFS (A) and OS (B) according to baseline PIV in external validation group. Yellow lines indicate patients with low PIV (<581.95), and blue lines indicate patients with high PIV (≥581.95). mOS, median overall survival; mPFS, median progression-free survival; m month; PIV, Pan-Immune-Inflammation Value.
Figure 5
Figure 5
Kaplan–Meier curves for PFS (A) and OS (B) according to baseline PILE in external validation group. Yellow lines indicate patients with low PILE (PLIE score = 0, 1); blue lines indicate patients with high PILE (PLIE score = 2, 3). mOS, median overall survival; mPFS, median progression-free survival; m, month.

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