Immune Checkpoint Inhibitors With or Without Bone-Targeted Therapy in NSCLC Patients With Bone Metastases and Prognostic Significance of Neutrophil-to-Lymphocyte Ratio

Abstract

IntroductionBone metastases (BMs) are a negative prognostic factor in patients with non-small cell lung cancer (NSCLC). Although immune-checkpoint inhibitors (ICIs) have dramatically changed the therapeutic landscape of NSCLC, little information is available on BMs from NSCLC treated with ICIs alone or in association with bone-targeted therapy (BTT) such as zoledronate or denosumab.MethodsFrom 2014 to 2020, 111 of the 142 patients with BMs secondary to NSCLC extrapolated from the prospective multicenter Italian BM Database were eligible for analysis. Information on blood count, comorbidities, and toxicity was retrospectively collected. The neutrophil-to-lymphocyte ratio (NLR) pre- and post-treatment was calculated. Survival was analyzed using the Kaplan–Meier method, with statistical significance of survival differences assessed using the log-rank test.ResultsMedian age was 66 (range, 42–84) years. Performance status (PS) Eastern Cooperative Oncology Group (ECOG) was 0–1 in 79/111 patients. The majority of patients (89.2%) had adenocarcinoma histology. At a median follow-up of 47.4 months, median progression-free (mPFS) and overall survival (mOS) was 4.9 (95%CI, 2.8–10.0) and 11.9 (95%CI, 8.2–14.4) months, respectively. Forty-six (43.4%) patients with BM NSCLC underwent first- or further-line therapy with ICIs: 28 (60.8%) received nivolumab, 9 (19.6%) pembrolizumab, and 9 (19.6%) atezolizumab. Of the 46 patients treated with ICIs, 30 (65.2%) underwent BTT: 24 (80.0%) with zoledronate and 6 (20.0%) with denosumab. The ICI-alone group had an mOS of 15.8 months [95%CI, 8.2–not evaluable (NE)] vs. 21.8 months (95%CI, 14.5–not evaluable) for the ICI plus BTT group and 7.5 (95%CI, 6.1–10.9) months for the group receiving other treatments (p < 0.001). NLR ≤5 had a positive impact on OS.ConclusionBTT appears to have a synergistic effect when used in combination with ICIs, improving patient survival.

Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: A retrospective chart review

“…Our study results were partly supported by previous data from Bongiovanni et al. ( 15 ), whose work indicated a better mPFS (15.9 months; 95%CI, 5.1–not estimable) of patients receiving denosumab (n = 6) than those treated with ICIs alone or with ZA ( p = 0.068).…”

“…However, treatment with ZA was confounded in the study arm, so the synergistic effect of denosumab and immunotherapy could not be accurately assessed. Furthermore, it is possible that the additional prolongation of survival in the experimental group shown by the study results was due to the survival benefit of BTT by reducing SREs rather than synergy with immunotherapy ( 15 ). A summary of published data on the combination of denosumab and ICIs is demonstrated in Table 5 .…”

Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors

“…In recent years, dNLR has been used as a novel biomarker to predict response to immunotherapy in various cancers including NSCLC, melanoma and head and neck cancers ( 39 , 40 ). It has been shown that a high pre-treatment dNLR (indicating a high inflammatory state) is associated with poor OS and PFS in a variety of cancers ( 37 , 39 – 42 ). For instance, Bongiovanni et al, observed a positive association between OS and a NLR ≤ 5 ( 42 ).…”

Bone Metastasis and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC): Microenvironment and Possible Clinical Implications

“…The retrospective analysis of data on 111 NSCLC patients extrapolated from the prospective Italian register of bone metastasis (BMDB) (from 2014 to 2020) confirmed, despite a limited number of patients treated with ICIs (n = 46), that the use of BTT (30 patients) with ICI monotherapy increases OS from 15.8 months to 21.8 months [ 38 ]. Regarding the response on bone evaluated with the MD Anderson criteria, 43.5% of patients obtained a partial response following ICIs plus BTT, while the same response was obtained in only 16.7% of patients treated with ICIs alone.…”