Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel.

INTRODUCTION: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.

Efficacy and safety of amrubicin monotherapy after atezolizumab plus carboplatin and etoposide in patients with relapsed small-cell lung cancer.

This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with atezolizumab plus carboplatin and etoposide (AteCE). This retrospective study evaluated patients with relapsed SCLC who were treated with previously AteCE combination therapy followed by amrubicin monotherapy between August 2019 and May 2021. Clinical efficacy and toxicity were analyzed. Overall, 40 patients were included: 12 and 28 patients had sensitive and refractory relapse, respectively. The response rate was 32.5% (25.0% in the sensitive group and 35.7% in the refractory group). The median progression-free survival (PFS) and overall survival (OS) from the first amrubicin treatment was 3.4 months (95% CI: 1.9-4.9 months) and 9.9 months (95% CI: 4.5-11.5 months), respectively. There was no significant between-group difference in median PFS (3.6 months vs. 3.2 months, p = 0.42) or median OS (11.2 months vs. 7.3 months, p = 0.78). Grade ≥ 3 hematological adverse events occurred as follows: decreased white blood cells in 52.5% of patients; decreased neutrophil count in 57.5%; and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. There were no treatment-related deaths. Amrubicin is feasible and effective for relapsed SCLC patients previously treated with AteCE therapy. Although immune checkpoint inhibitor treatment (ICI) does not improve the effect of amrubicin, the toxicity is not increased, suggesting that amrubicin remains effective even after ICI administration. Thus, amrubicin after AteCE could be the preferred standard chemotherapeutic choice in patients with relapsed SCLC.

Efficacy and Safety of First-line Pembrolizumab Plus Platinum and Pemetrexed in Elderly Patients with Non-squamous Non-small-cell Lung Cancer.

Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer.

PURPOSE: The aim of this study was to assess the effectiveness and tolerability of atezolizumab plus carboplatin and etoposide combination chemotherapy in elderly patients with extensive-disease (ED) small-cell lung cancer (SCLC). METHODS: This retrospective study evaluated 65 SCLC patients who received atezolizumab, carboplatin, and etoposide for ED-SCLC in nine study institutions between August 2019 and September 2020. Clinical efficacy, assessed according to response rate and survival, and toxicity were compared between the elderly (n = 36 patients; median age: 74 years [range: 70-89 years]) and the non-elderly group (n = 29 patients; median age: 67 years [range: 43-69 years]). RESULTS: The response rate was 73.8% (80.5% in the elderly group and 65.5% in the non-elderly group). There was no significant difference in both the median progression-free survival (5.5 months vs. 4.9 months, p = 0.18) and the median overall survival (15.4 months vs. 15.9 months, p = 0.24) between the elderly group and the non-elderly group. The frequencies of grade ≥3 hematological adverse events in the elderly patients were as follows: decreased white blood cells, 36.1%; decreased neutrophil count, 61.1%; decreased platelet count, 8.3%; and febrile neutropenia, 8.3%. One treatment-related death due to lung infection occurred in the elderly group. CONCLUSION: Despite hematologic toxicities, especially decreased neutrophil count, atezolizumab, carboplatin, and etoposide combination chemotherapy demonstrates favorable effectiveness and acceptable toxicity in elderly patients. Thus, atezolizumab plus carboplatin and etoposide could be the preferred standard treatment modality for elderly patients with ED-SCLC.

Using the neutrophil-to-lymphocyte ratio to predict the outcome of individuals with nonsquamous non-small cell lung cancer receiving pembrolizumab plus platinum and pemetrexed.

BACKGROUND: Factors predicting the response to pembrolizumab plus platinum and pemetrexed combination therapy (Pemb-Plt-PEM) in nonsquamous non-small cell lung cancer (non-sq NSCLC) are unclear. We investigated the Glasgow Prognostic (GP) score, neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) as predictors of response to initial treatment with combination therapy in individuals with advanced non-sq NSCLC. METHODS: We retrospectively reviewed 236 patients who received initial treatment with combination therapy for non-sq NSCLC at 13 institutions between December 2018 and December 2020. The usefulness of the GP score, NLR, and BMI as prognostic indicators was assessed. Cox proportional hazard models and the Kaplan-Meier method were used to compare progression-free survival (PFS) and overall survival (OS). RESULTS: The response rate was 51.2% (95% CI: 44.9-57.5%). The median PFS and OS after beginning Pemb-Plt-PEM were 8.8 (95% CI: 7.0-11.9) months and 23.6 (95% CI: 18.7-28.6) months, respectively. The NLR independently predicted the efficacy of Pemb-Plt-PEM-the PFS and OS were more prolonged in individuals with NLR <5 than in those with NLR ≥5 (PFS: 12.8 vs. 5.3 months, p = 0.0002; OS: 29.4 vs. 12.0 months, p < 0.0001). BMI predicted the treatment response-individuals with BMI ≥22.0 kg/m2 had longer OS than did those with BMI < 22.0 kg/m2 (OS: 28.4 vs. 18.4 months, p = 0.0086). CONCLUSIONS: The NLR significantly predicted PFS and OS, whereas BMI predicted OS, in individuals who initially received Pemb-Plt-PEM for non-sq NSCLC. These factors might be prognosis predictors in non-sq NSCLC.

Predictive value of post-treatment C-reactive protein-to-albumin ratio in locally advanced non-small cell lung cancer patients receiving durvalumab after chemoradiotherapy.

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.

Post-progression survival after atezolizumab plus carboplatin and etoposide as first-line chemotherapy in small cell lung cancer has a significant impact on overall survival.

BACKGROUND: The effect of first-line chemotherapy on overall survival (OS) may be significantly influenced by subsequent therapy for patients with extensive disease small cell lung cancer (ED-SCLC). Therefore, we evaluated the relationship between progression-free survival (PFS), post-progression survival (PPS), and OS of ED-SCLC patients treated with atezolizumab plus carboplatin and etoposide as first-line therapy. METHODS: We analyzed the data of 57 patients with relapsed ED-SCLC treated with atezolizumab plus carboplatin and etoposide (AteCE) as first-line chemotherapy between August 2019 and September 2020. The respective correlations between PFS-OS and PPS-OS following first-line AteCE treatment were examined at the individual patient level. RESULTS: Spearman's rank correlation analysis and linear regression analysis showed that PPS strongly correlated with OS (r = 0.93, p < 0.05, R2  = 0.85) and that PFS moderately correlated with OS (r = 0.55, p < 0.05, R2  = 0.28). Performance status at relapse (0-1/≥2), number of cycles of atezolizumab maintenance therapy (<3/≥3), and platinum rechallenge chemotherapy all significantly positively correlated with PPS (p < 0.05). CONCLUSIONS: Upon comparing OS-PFS and OS-PPS in this patient population, OS and PPS were found to have a stronger correlation. These results suggest that performance status at relapse, atezolizumab maintenance, or chemotherapy rechallenge could affect PPS.

Pretreatment glasgow prognostic score predicts survival among patients administered first-line atezolizumab plus carboplatin and etoposide for small cell lung cancer.

Background: There are no established predictive biomarkers for the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with small-cell lung cancer (SCLC). Therefore, the current study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC. Methods: We reviewed data from 84 patients who received first-line atezolizumab plus carboplatin and etoposide therapy for SCLC at nine Japanese institutions between August 2019 and May 2021. Further, we evaluated the prognostic value of the GPS, NLR, and BMI. The Kaplan-Meier and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). Moreover, the GPS, NLR, and BMI consisted of C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively. Results: The response rate was 72.6% (95% confidence interval: 63.0-82.1%). The median PFS and OS from the initiation of treatment were 5.4 (95% CI: 4.9-5.9) months and 15.4 (95% CI: 11.4-16.8) months, respectively. The GPS independently predicted the effectiveness of first-line atezolizumab plus carboplatin and etoposide treatment, as a favorable GPS (GPS 0-1) was correlated with significantly better PFS and OS rates compared to a poor GPS (GPS 2) (PFS: 5.8 vs. 3.8 months, p = 0.0005; OS: 16.5 vs. 8.4 months, p<0.0001). Conclusions: This is the first analysis to evaluate the association between the GPS, NLR, and BMI and the treatment effectiveness of survival among patients receiving first-line atezolizumab plus carboplatin and etoposide therapy for SCLC. Among patients receiving this treatment for SCLC, GPS was significantly associated with the PFS and OS rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients.

Beneficial impact of weight loss on respiratory function in interstitial lung disease patients with obesity.

BACKGROUND: Interstitial lung disease (ILD) patients commonly become obese or overweight due to deteriorated daily living activities and the adverse effects of prednisolone. This study aimed to clarify the effect of weight loss on pulmonary function test (PFT) in ILD patients with obesity. METHODS: Among all consecutive ILD patients with a body mass index (BMI) ≥ 27 kg/m2 who received nutrition education for improving obesity between June 2014 and December 2018, we retrospectively included patients who successfully decreased their body weight by over 2 kg and underwent follow-up PFT within 6 months. The results of PFT at baseline and follow-up and the level of Krebs von den Lungen-6 (KL-6) were compared. RESULTS: Eleven patients (5 men and 6 women; median BMI of 34.1 kg/m2), were enrolled. For PFT at baseline, the percentages of forced vital capacity (%FVC), functional residual capacity (%FRC), and diffusing capacity of the lung for carbon monoxide (%DLCO) were 69.3%, 59.9%, and 54%, respectively. The median KL-6 was 1035 U/mL. The median interval from baseline to the follow-up PFTs was 41 days. Compared to the baseline results of PFT, %FVC, %FRC, and %DLCO significantly increased (p = 0.018, 0.0006, and 0.024, respectively), and the changes in body weight and FVC were strongly correlated (p = 0.0004). In addition, the median serum level of KL-6 at follow-up tended to decrease by 206.5 U/mL (p = 0.083). CONCLUSION: In ILD patients with obesity, weight loss is important and potentially improves their disease course.

Efficacy and safety of S-1 monotherapy in previously treated elderly patients (aged ≥75 years) with non-small cell lung cancer: A retrospective analysis.

BACKGROUND: S-1 monotherapy is effective and feasible for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, it is not clear whether its effectiveness and tolerability in elderly patients are equivalent to those in younger patients. Hence, this study aimed to evaluate the efficacy and feasibility of S-1 monotherapy in elderly patients with NSCLC who had previously received other treatments. METHODS: We included 96 elderly patients (aged ≥75 years) with advanced NSCLC treated with S-1 alone as a subsequent-line treatment at 12 medical facilities between January 2005 and March 2018 in this study. The baseline characteristics of the patients, response to S-1 monotherapy, and adverse events (AEs) were investigated, retrospectively. RESULTS: A total of 68 male and 28 female patients (median age, 78 [range: 75-86] years) were analyzed. In elderly patients who were treated with S-1 monotherapy as a subsequent-line treatment, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 8.3%, 43.8%, 3.4 months, and 9.6 months, respectively. Observed AEs included anorexia, anemia, nausea, fatigue, reduced platelet count, and skin hyperpigmentation. Treatment-related death was observed in one patient because of pneumonitis. In patients who experienced no progressive disease, subsequent-line S-1 alone was associated with longer PFS and OS. CONCLUSIONS: S-1 monotherapy is effective and feasible as a subsequent-line treatment in elderly patients who were previously treated for NSCLC, and it produces results. S-1 monotherapy could be one of the treatment choices for elderly patients with previously treated NSCLC.

Efficacy and safety of first-line pembrolizumab monotherapy in elderly patients (aged ≥ 75 years) with non-small cell lung cancer.

PURPOSE: Pembrolizumab is an effective front-line treatment for advanced non-small cell lung cancer (NSCLC) in patients expressing high levels of programmed death-ligand 1 (PD-L1). However, it is unclear whether first-line pembrolizumab has similar efficacy among elderly (aged ≥ 75 years) and younger patients. This study aimed to investigate the safety and efficacy of front-line pembrolizumab monotherapy in older adults with NSCLC expressing high PD-L1. METHODS: A total of 128 patients with advanced NSCLC expressing high PD-L1, including 47 older adults, received first-line pembrolizumab monotherapy at ten institutions in Japan, between February 2017 and February 2018. Data related to patient characteristics, efficacy of pembrolizumab therapy, and the type and severity of adverse events were recorded. RESULTS: Overall, 47 patients [40 men and 7 women; median age 79 (range 75-88) years] were included in our analysis. In patients who received first-line pembrolizumab monotherapy, overall response, disease control rates, median progression-free survival (PFS), and median overall survival (OS) were 53.1%, 74.4%, 7.0 months, and not reached, respectively. Common adverse events included anorexia, fatigue, skin rash, and hypothyroidism. Two treatment-related deaths were noted, due to pneumonitis and infection. First-line pembrolizumab monotherapy was associated with improved PFS in patients with non-progressive disease (PD). In patients with non-PD and good performance status (PS), pembrolizumab monotherapy improved OS. CONCLUSIONS: Elderly patients with NSCLC expressing high PD-L1 tolerated front-line pembrolizumab monotherapy well. Their survival outcomes were equivalent to those of younger patients. In patients with non-PD, first-line pembrolizumab monotherapy may improve PFS; in conjunction with good PS, it additionally improves OS.

Efficacy and safety of immune checkpoint inhibitor monotherapy in pretreated elderly patients with non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibitors (ICIs) are an effective subsequent-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether the efficacy and safety of subsequent-line ICI monotherapy in elderly patients (aged ≥ 75 years) are similar to that in non-elderly patients. Therefore, we aimed to investigate the efficacy and safety of ICI monotherapy in pretreated elderly patients with NSCLC. METHODS: Between January 2016 and February 2018, 131 elderly patients with advanced NSCLC who received subsequent-line ICI monotherapy at 13 Japanese institutions were enrolled in this study. Baseline characteristics, the efficacy of ICI treatment, and adverse events were evaluated. RESULTS: Ninety-eight men and 33 women (median age 77 [range 75-87] years) were enrolled. Among those who received subsequent-line ICI monotherapy, the overall response, disease control rates, median progression-free survival (PFS), and overall survival (OS) were 27.4%, 61.8%, 4.5 months, and 16.0 months, respectively. Adverse events such as anorexia, fatigue, pneumonitis, and hypothyroidism were observed. There were two treatment-related deaths due to pneumonitis and thrombocytopenia. Subsequent-line ICI monotherapy in patients with good performance status (PS), receiving steroids for immune-related adverse events (irAEs), and exhibiting partial response (PR) was associated with improved PFS, as well as OS in patients with good PS and PR. CONCLUSIONS: Subsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition.