Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Abstract

Background: This study aimed to investigate the association of computed tomography (CT)-assessed sarcopenia and visceral adiposity with efficacy and prognosis of immune-checkpoint inhibitor (ICI) therapy for pretreated non-small cell lung cancer (NSCLC). Methods: We retrospectively collected 74 patients with pretreated NSCLC who had initiated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor monotherapy between December 2015 and November 2018 at our hospital. As CT-assessed pretreatment markers, we used psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), visceral-tosubcutaneous ratio (VSR) and visceral fat area (VFA) at lumbar vertebra L3 level. We divided 74 patients into high and low groups according to each Japanese sex-specific cutoff value. Using Kaplan-Meier curves and log-rank tests, we compared overall survival (OS) and progression-free survival (PFS). Adjusted by serum albumin, neutrophil-to-lymphocyte ratio, performance status and driver mutations, multivariate Cox proportional hazard analyses evaluated various variables as independent prognostic factors of OS and PFS. Results: We could not find significant difference in response rate (RR) and disease control rate (DCR) between low and high groups according to any factors. The OS of patients with body mass index (BMI) < 18.5 was significantly shorter than that of patients with BMI ≥ 18.5 (median 3.3 vs. 15.8 months, P < 0.01), while there was no significant difference in OS and PFS according to PMI, IMAC, VSR and VFA. Multivariate analyses detected no significant prognostic factor in OS and PFS, except for low IMAC (hazard ratio 0.43, 95% confidence interval 0.18-0.998, P = 0.0496) as a favorable prognostic factor of longer OS. Conclusions: Neither PMI nor VSR, VFA might be a significant prognostic factor of PFS and OS of ICI monotherapy for pretreated NSCLC. According to our multivariate analyses, IMAC was a significant prognostic factor of OS, but not of PFS. Thus, neither sarcopenia nor visceral adiposity may be associated with the efficacy of ICI therapy.

Sarcopenia and Visceral Adiposity Are Not Independent Prognostic Markers for Extensive Disease of Small-Cell Lung Cancer: A Single-Centered Retrospective Cohort Study

“…However, to our knowledge, ours was the first study that had directly focused on visceral adiposity in SCLC. Our results were consistent with our previous studies of NSCLCs treated with epidermal growth factor receptor-tyrosine kinase inhibitors [ 15 ] or with immune checkpoint inhibitor monotherapy [ 16 ]. Thus, our series of studies doubted visceral adiposity as a prognostic factor for various types of lung cancer.…”

“…We collected the following data: sex, age, BMI, smoking habits, Eastern Cooperative Oncology Group (ECOG) performance status (PS), distant metastases, venous blood test, treatment regimens, response of the first-line chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ 14 ], progression-free survival (PFS) and OS. Our definitions of response rate (RR), disease control rate (DCR), PFS and OS followed those in our previous studies [ 15 , 16 ]. The data was cut-off on December 31, 2019.…”

“…We also manually traced the bilateral multifidus muscles areas. The definitions and the Japanese sex-specific cut-off points of PMI [ 18 ], IMAC [ 19 ] and VSR [ 20 ] followed those of our previous studies [ 15 , 16 ].…”

Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

“…Likewise, while the role of low muscle quality in immunotherapy is currently a hot research topic, no conclusions have been drawn to date. While a previous study stated that decreased lumbar muscle density is predictive of inferior PFS in patients with metastatic melanoma treated with ipilimumab, 25 several other studies conducted in patients with metastatic NSCLC treated with PD‐1/PD‐L1 inhibitors were skeptical about its predictive value 10,17 . Cortellini et al retrospectively reviewed the impact of muscle quality on PFS in association with PD‐1/PD‐L1 inhibitor use in a mixed cancer population comprising 46 patients with advanced NSCLC and 54 patients with other advanced cancers including renal cell carcinoma and melanoma 14 .…”

“…They measured lumbar skeletal muscle density as an indicator of muscle quality and showed no association between muscle quality and PFS or ORR. Minami et al retrospectively reviewed 74 patients with pretreated and advanced NSCLC who had received PD‐1/PD‐L1 inhibitor therapy 17 . They used the intramuscular adipose tissue content in the multifidus muscle as an indicator of muscle quality and reported the absence of impact on PFS.…”