Background: Nivolumab is a second‐line chemotherapy for non‐small cell lung cancer (NSCLC). This study explored the impact of clinical biomarkers such as neutrophil:lymphocyte ratio (NLR), C‐reactive protein:albumin ratio (CAR), and modified Glasgow prognostic score on the efficacy and outcome of nivolumab monotherapy in previously treated NSCLC patients.Methods: We retrospectively analyzed advanced or postoperative recurrence of NSCLC in 113 patients in two Japanese facilities from January 2015 to December 2019. Optimal cutoff values of NLR and CAR were assessed by the area under the receiver operating characteristic curves predicting death events to conduct regression analysis. Baseline values and values collected eight weeks after nivolumab treatment were measured to investigate time‐series changes of these markers.Results: The patients showed median overall survival (OS) and progression‐free survival (PFS) of 14.0 months and 2.3 months, respectively, with both being significantly longer in patients with partial response (PR) than in patients with progressive disease (PD). Optimal cutoff levels for NLR and CAR were 5.8 and 0.83, with significant decrease in CAR (P = 0.002) from baseline levels in PR patients and significant increase in PD patients. Baseline CAR ≥0.83 was significantly associated with one‐year mortality events and overall survival (OS), and multivariate analysis showed significant association of age ≤70 years, an Eastern Cooperative Oncology Group performance status score of 2 or 3, and a baseline CAR ≥0.83 with inferior OS.Conclusions: For second‐line nivolumab therapy, evaluation of baseline CAR and subsequent changes in CAR may be predictive of therapeutic response to nivolumab and long‐term survival in NSCLC patients.Key points: Significant findings of the studyThe baseline value of C‐reactive protein:albumin ratio was significantly associated with one‐year mortality and overall survival in non‐small cell lung cancer patients treated with nivolumab.What this study addsTime‐series change of C‐reactive protein:albumin ratio may be useful for predicting the treatment efficacy in patients treated with nivolumab.

Background: The lung immune prognostic index (LIPI) is a marker that combines the derived neutrophil‐to‐lymphocyte ratio (dNLR) and serum lactate dehydrogenase (LDH) level and is a recently reported prognostic factor of immune checkpoint inhibitor therapy for non‐small cell lung cancer (NSCLC). However, there are no reports regarding the prognostic value of LIPI in small cell lung cancer (SCLC).Methods: We retrospectively enrolled 171 patients diagnosed with SCLC and treated at Shinshu University School of Medicine between January 2003 and November 2019. Progression‐free survival (PFS) and overall survival (OS) were compared according to LIPI, and we investigated whether LIPI could be a prognostic factor in SCLC using the Kaplan‐Meier method and univariate and multivariate Cox models.Results: The median OS of the LIPI 0 group was significantly longer than that of the LIPI 1 plus 2 group (21.0 vs. 11.6 months, P < 0.001). The multivariate analysis associated with OS indicated that LIPI 1 plus 2 was an independent unfavorable prognostic factor in addition to poor performance status (2–3), old age (≥ 75 years) and stage (extensive disease [ED]). However, PFS of the LIPI 0 group was not significantly different from that of the LIPI 1 plus 2 group. In ED‐SCLC patients, the median PFS and OS of the LIPI 0 group were significantly longer than those of the LIPI 2 group (6.6 vs. 4.0 months, P = 0.006 and 17.1 vs. 5.9 months, P < 0.001, respectively).Conclusions: We confirmed the prognostic value of LIPI in SCLC, especially ED‐SCLC.Key points: Significant findings of the study: The present study is the first to demonstrate that pretreatment lung immune prognostic index is an independent prognostic factor associated with overall survival for small cell lung cancer. What this study adds: The utility of the lung immune prognostic index as a prognostic factor for small cell lung cancer.

Background: The geriatric nutritional risk index (GNRI) is a simple and useful marker for predicting prognosis and treatment efficacy among patients with various cancers. However, to the best of our knowledge, there are no previous reports regarding the prognostic value of GNRI among patients with non‐small cell lung cancer (NSCLC) who were treated with immune checkpoint inhibitors (ICIs).Methods: We retrospectively evaluated 85 patients with previously treated advanced NSCLC who were administered ICIs at Shinshu University Hospital between February 2016 and October 2020. Progression‐free survival (PFS) and overall survival (OS) were compared between groups with high (≥89.5) and low (<89.5) GNRI values. We used univariate and multivariate Cox regression analyses to identify prognostic factors that were associated with PFS and OS.Results: The high and low GNRI groups included 61 and 24 patients, respectively. Relative to the low GNRI group, the high GNRI group had significantly longer median PFS (3.7 vs. 2.4 months, p = 0.041) and significantly longer median OS (14.2 vs. 6.1 months, p = 0.008). Multivariate analyses revealed that independent predictors of favorable OS were high GNRI, performance status of 0–1, and age of ≥70 years. The high GNRI group was significantly more likely to undergo subsequent therapy after immunotherapy (68.6 vs. 33.3%, p = 0.008).Conclusions: The present study revealed that high GNRI was associated with good outcomes among patients with previously treated NSCLC who were treated with ICIs.

Purpose: Similar to the neutrophil-to-lymphocyte ratio and lung immune prognostic index (LIPI), immune-related adverse events (irAEs) were favorable prognostic factors in several studies, for patients with non-small cell lung cancer who received immune checkpoint inhibitors (ICIs). However, few studies have investigated patient characteristics and markers that predict the development of irAEs, and factors predicting the development of irAEs have not been clarified. Thus, the present study aimed to examine the predictive factors correlated with the development of irAEs in non-small cell lung cancer (NSCLC) patients who received anti-programmed cell death protein 1/programmed cell death ligand 1 inhibitor monotherapy. Patients and Methods: The present study was retrospectively enrolled 113 advanced NSCLC patients who received ICIs between February 2016 and May 2021 and was conducted at Shinshu University Hospital. All patients were divided into two groups according to with or without of irAEs. We compared the clinical findings and laboratory data between the two groups and considered predictive factors correlated with the development of irAEs. Results: Forty-four (38.9%) patients developed irAEs of any grade. The most common irAEs were hypothyroidism (12.4%), followed by skin rash (7.1%) and interstitial lung disease (7.1%). The survival time in patients with irAEs was significantly more prolonged compared to those without irAEs (median progression-free survival: 6.8 vs 2.1 months, p < 0.001; median overall survival: 25.3 vs 9.6 months, p = 0.001). Multivariate analyses based on logistic regression revealed independent predictive factors that correlated with the development of irAEs to be first-line ICI treatment and a score of 0 or 1 on LIPI. Conclusion: The present study revealed that lines of immunotherapy and LIPI were correlated with the development of irAEs in NSCLC patients who received ICIs and can help clinicians who manage patients experiencing irAEs receiving ICIs.

Background: Combination immunotherapy (immune checkpoint inhibitors and cytotoxic anticancer agents) is widely used as first-line treatment for advanced non-small cell lung cancer (NSCLC). However, the therapeutic effect of combination immunotherapy has not been fully investigated. C-reactive protein, performance status, lactate dehydrogenase, albumin, and derived neutrophil-to-lymphocyte ratio (C-PLAN) are useful biomarkers for predicting the prognosis of NSCLC; however, there are no reports examining the C-PLAN index, which combines these five factors in a single prognostic factor.Methods: We retrospectively collected data from 178 patients with previously untreated advanced NSCLC who received combination immunotherapy at multicenter institutions in Nagano Prefecture between December 2018 and April 2022. We investigated the utility of the C-PLAN index as a prognostic factor using Cox regression analysis and correlated it with survival.Results: The good and poor C-PLAN index groups included 85 and 93 patients, respectively. The good C-PLAN index group had a longer median progression-free survival (PFS) (10.7 vs. 6.0 months; p = 0.022) and overall survival (OS) (25.3 vs. 16.5 months; p = 0.003) than the poor C-PLAN index group. The C-PLAN index was an independent favorable prognostic factor that correlated with PFS and OS in multivariate analysis. The good C-PLAN index group had a higher proportion of never-smokers (16.5 vs. 4.3%; p = 0.007) and stage III disease/postoperative recurrence (32.9 vs. 15.1%; p = 0.005) than the poor C-PLAN index group.Conclusion: The C-PLAN index is a useful prognostic factor for patients with previously untreated advanced NSCLC undergoing combination immunotherapy.

Backgrounds: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non–small cell lung cancer (LA‐NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation‐related parameters in patients with LA‐NSCLC treated with CCRT plus durvalumab.Methods: We recruited 76 LA‐NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein‐to‐albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre‐treatment) and 2 months after (post‐treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression‐free survival (PFS) after durvalumab therapy.Results: The median follow‐up time was 17 (range, 3.3–35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non‐infectious pneumonitis being the most common reason. Post‐treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not‐reached vs. 9.6 months. Log‐rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post‐treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003).Conclusions: This study suggests that post‐treatment CAR has predictive value for LA‐NSCLC patients treated with CCRT plus durvalumab consolidation therapy.