Lower tumor volume is associated with increased benefit from immune checkpoint inhibitors in patients with advanced non‐small‐cell lung cancer

Abstract

Aim: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced nonsmall-cell lung cancer (NSCLC), yet many patients do not benefit from Programmed cell death protein 1 (PD-1) axis inhibitors, emphasizing the need for additional markers for better patient selection. Our aim was to evaluate the association between tumor volume and response to ICI. Methods: This retrospective ethically-approved study included all consecutive patients with advanced NSCLC who were evaluated with a fluorodeoxyglucose-positron emission tomography scan, prior to the first administration of a single-agent ICI between 1/2016 and 6/2017. Tumor burden was calculated based on total body metabolic tumor volume and sum of all measurable lesions (SOML). Results: Median SOML was 88 mm, and was inversely and significantly associated with progression-free survival (PFS) (hazard ratio [HR] 2, CI 1.28-3.37, P = .003) and overall survival (OS) (HR 2.36, CI 1.13-4.94, P = .02). SOML≤80 mm had a significantly longer PFS compared to patients with a SOML≥80 mm (median PFS 9.7 vs 3.7 months, respectively, HR for progression 2.26, CI 1.1-4.5, P = .02). Patients with a SOML≤80 also had longer median OS compared to patients with SOML≥80 (median OS 12 vs 9.8 months, respectively, HR for death 3.1, CI 1.2-8, P = .018). Conclusions: Low tumor burden was associated with higher response rates (RR), and better PFS and OS in advanced NSCLC patients treated with ICI. These results may improve the selection of patients for treatment with single-agent ICI, as opposed to the combination with chemotherapy, which might be more appropriate for patients with high tumor burden. Prospective analysis is warranted.

Predictive value of baseline metabolic tumor volume for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis

“…Four studies were conducted in France ( 20 , 22 , 26 , 27 ), followed by three in Italy ( 16 , 18 , 21 ) and three in Japan ( 16 , 18 , 21 ). We also identified a single study in the United States ( 19 ), Israel ( 24 ) and Belgium ( 28 ). Two studies were of a prospective design ( 18 , 20 ).…”

“…Two studies were of a prospective design ( 18 , 20 ). SUV, MTV and TLG were measured in four studies ( 18 , 20 , 25 , 28 ) and MTV alone was measured in five studies ( 17 , 19 , 21 , 22 , 24 ).…”

“…Patients were divided into high or low SUV/MTV/TLG groups in each study based on the cut-off values, and their PFS/OS were analyzed. And eleven of the thirteen studies used median MTV/TLG as cut-off values (16,(18)(19)(20)(21)(22)(24)(25)(26)(27)(28). The left two used log-rank test (23) and receiver operating characteristic (ROC) curve analysis (17) to determine cut-off values, respectively.…”

“…Thirteen studies (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) analyzed the relationship between MTV and PFS/OS, as shown in Figure 5. The cut-off values of MTV ranged from 5.0 to 268.0cm 3 , so we performed a subgroup analysis based on the cut-off values, dividing them into three groups: MTV < 50cm 3 , MTV between 50-100cm 3 , and MTV >100cm 3 .…”

Predictive Value of Baseline FDG-PET/CT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors

“…Thirteen original manuscripts have been published between 2020 and 2022 on the predictive value of FDG-PET/CT in NSCLC patients, along with a meta-analysis [ 4 , 12 , 15 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Our study is different in many aspects from these previously published data.…”