Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations.

Introduction: Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, is the standard treatment for patients with naive EGFR-mutant NSCLC. Nevertheless, information on how the mutation subtype affects disease progression after the failure of OSI treatment is scarce. Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC who received OSI as a first-line treatment between April 2015 and December 2021. Results: This study included 229 patients. The objective response rate was 71%, with intracranial and extracranial response rates of 71% and 90%, respectively. The median progression-free survival was 23.3 mo (95% confidence interval [CI]: 19.6-26.7), and the median overall survival was 33.7 mo (95% CI: 31.3-58.6). Multivariate analysis revealed that the EGFR exon 21 L858R point mutation (L858R) (hazard ratio [HR] = 1.56, 95% CI: 1.04-2.34, p = 0.0328) and liver metastasis (HR = 2.63, 95% CI: 1.53-4.49, p = 0.0004) were significant predictors of progression-free survival in OSI treatment. The concomitant disease progression involving the central nervous system metastasis was significantly more common in patients with L858R (p = 0.048), whereas concomitant disease progression involving primary lesions was significantly more common in patients with exon 19 deletion mutation (p = 0.01). In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, p = 0.027). Conclusions: The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations.

Investigation of a practical assessment index to capture the clinical presentation of cachexia in patients with lung cancer.

OBJECTIVE: Cancer cachexia constitutes a poor prognostic factor in patients with lung cancer. However, the factors associated with cancer cachexia remain unclear. This study aimed to identify factors that influence cancer cachexia in patients with lung cancer. METHODS: In this retrospective observational study conducted at the Kansai Medical University, 76 patients with lung cancer were evaluated for physical function, nutritional status (Mini Nutritional Assessment-Short Form) and physical activity (International Physical Activity Questionnaire-Short Form) at the first visit to the rehabilitation outpatient clinic. The patients were divided into cachexia and noncachexia groups. The log-rank tests and Cox proportional hazards model were used to investigate the relationship between cachexia and prognosis. To examine the factors that influence cachexia, multivariate regression analysis with significant (P < 0.05) variables in the univariate logistic regression analysis was performed. Spearman's correlation analysis was performed to investigate the association between International Physical Activity Questionnaire-Short Form and performance status. RESULTS: Overall, 42 patients (55.2%) had cachexia associated with survival time since their first visit to the outpatient rehabilitation clinic, even after confounders adjustment (hazard ratio: 3.24, 95% confidence interval: 1.12-9.45, P = 0.031). In the multivariate analysis, Mini Nutritional Assessment-Short Form (odds ratio: 20.34, 95% confidence interval: 4.18-99.02, P < 0.001) and International Physical Activity Questionnaire-Short Form (odds ratio: 4.63, 95% confidence interval: 1.20-17.89, P = 0.026) were identified as independent factors for cachexia. There was no correlation between International Physical Activity Questionnaire-Short Form and performance status (r = 0.155, P = 0.181). CONCLUSION: Malnutrition and low physical activity were associated with cachexia in patients with lung cancer. The International Physical Activity Questionnaire-Short Form may be a useful indicator of physical activity in cachexia. Regularly assessing these factors and identifying suitable interventions for cachexia remain challenges to be addressed in the future.

Distinct metastatic spread and progression patterns in patients treated with crizotinib for ROS1- and ALK-rearranged non-small cell lung cancer: a single-center retrospective study.

Background: Crizotinib has been approved for C-ros oncogene 1 (ROS1)- and anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients. Few studies have examined the differences in crizotinib treatment outcomes between these patients and the progression sites during treatment. We investigated the metastatic spread, crizotinib efficacy, and progression patterns during crizotinib treatment in ROS1- and ALK-rearranged NSCLC patients. Methods: We retrospectively reviewed crizotinib-treated ROS1- and ALK-rearranged NSCLC patients between January 2011 and March 2021. Patient characteristics, clinical outcomes, and progression patterns during treatment were collected from medical records. The metastasis extent, crizotinib response, and progression patterns between the groups were compared. Results: We identified 26 patients with ROS1- and 42 with ALK-positive NSCLC. The baseline proportion of central nervous system (CNS) metastases did not differ between the groups (12% vs. 29%, P=0.10), but the proportion of extrathoracic metastases, including CNS metastases, was significantly higher in ALK-positive than in ROS1-positive NSCLC patients (35% vs. 71%, P=0.003). Regarding the response to crizotinib, the objective response rate (ORR), progression-free survival (PFS), or overall survival (OS) did not significantly differ between the groups (ROS1 vs. ALK, ORR: 69% vs. 69%, P=0.987; PFS: median 10.9 vs. 10.7 months, P=0.232; median OS: not reached vs. 67.7 months, P=0.495). The CNS was the most common metastasis site in both groups [ROS1 vs. ALK, 69% (11/16) vs. 46% (17/37), P=0.127], and the cumulative incidence of CNS metastasis did not differ between the groups (P=0.914). Conclusions: Crizotinib treatment outcomes, including progression patterns, were similar between ROS1- and ALK-positive NSCLC patients.

Disease progression status during initial immune checkpoint inhibitor (ICI) affects the clinical outcome of ICI retreatment in advanced non-small cell lung cancer patients.

BACKGROUND: It is still unclear whether patients with advanced non-small cell lung cancer (NSCLC), with disease progression after initial immune checkpoint inhibitor (ICI) therapy, would benefit from ICIs readministration. PATIENTS AND METHODS: We retrospectively collected data from patients with advanced NSCLC who received ICI retreatment. Depending on the disease status at the discontinuation of the initial ICI therapy, the patients were divided into two groups: with disease progression (PD group) and without disease progression (Without PD group). Patients in the Without PD group were required to experience disease progression during the treatment-free period. Efficacy was assessed by measuring the objective response rate (ORR) and progression-free survival in retreatment (PFS-R), while safety was assessed using the incidence of immune-related adverse events (irAEs). RESULTS: 30 (46.7%) of 64 eligible patients were included in the PD group and 34 (53.1%) in the Without PD group. Patients in the Without PD group had better clinical outcomes than those in the PD group (ORR, 29.4% vs. 6.7%; p = 0.03, median PFS-R, 4.1 months vs. 2.2 months, hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.36-1.04; p = 0.07). Multivariate Cox regression analysis showed that patients in the Without PD group had significantly longer PFS-R than those in the PD group (HR 0.42, 95% CI, 0.21-0.85; p = 0.015). In terms of safety, 28.1% of patients observed irAEs during ICI retreatment, and the incidence rate of grade 3 or higher irAEs was 7.8%. Specifically, of the 28 patients who discontinued their initial ICI treatment because of irAEs, 35.7% developed irAEs, and 28.6% experienced relapsed irAEs during ICI retreatment. CONCLUSION: Immune checkpoint inhibitor retreatment demonstrated efficacy in patients who discontinued initial ICI therapy for reasons other than disease progression. However, ICI retreatment was ineffective in patients with disease progression during the initial ICI treatment.

Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer.

OBJECTIVES: Ramucirumab, an anti-vascular endothelial growth factor receptor-2 antibody, has been approved for the treatment of non-small cell lung cancer (NSCLC); however, its pharmacokinetic properties in clinical practice are unknown. We aimed to measure ramucirumab concentrations and conduct a retrospective pharmacokinetic analysis using real-world data. MATERIALS AND METHODS: Patients with stage III-IV and recurrent NSCLC who received ramucirumab plus docetaxel were evaluated in this study. After the first administration, the ramucirumab trough concentration (Ctrough) was measured using liquid chromatography-mass spectrometry. Patient characteristics, adverse events, tumor response, and survival time were retrospectively extracted from medical records from August 2, 2016 to July 16, 2021. RESULTS: A total of 131 patients were examined to assess serum ramucirumab concentrations. Ctrough ranged from below the lower limit of quantification (BLQ) to 48.8 µg/mL (BLQ ≤ 1st quartile (Q1) ≤ 7.34, 7.34 < 2nd quartile (Q2) ≤ 14.7, 14.7 < 3rd quartile (Q3) ≤ 21.9 and 21.9 < 4th quartile (Q4) ≤ 48.8 µg/mL). The overall response rate was significantly higher in Q2-4 than that in Q1 (p = 0.011). The median progression-free survival was marginally longer, and overall survival was significantly longer in Q2-4 (p = 0.009). The Glasgow prognostic score (GPS) in Q1 was significantly higher than in Q2-4 (p = 0.034) and associated with Ctrough (p = 0.002). CONCLUSION: Patients with higher ramucirumab exposure had a high ORR and prolonged survival time, whereas patients with lower ramucirumab exposure were characterized by a high GPS and poor prognosis. Cachexia may reduce the exposure level of ramucirumab in certain patients, reducing the clinical benefits of ramucirumab treatment.

Prognostic role of modified Glasgow Prognostic score in elderly non-small cell lung cancer patients treated with anti-PD-1 antibodies.

BACKGROUND: This study aimed to investigate whether the immunosenescence-related score is a critical prognostic predictor of anti-programmed cell death protein 1 (PD-1) axis inhibitors in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: We reviewed 51 patients with advanced NSCLC aged ≥75 years, who were treated with nivolumab or pembrolizumab at the National Cancer Center Hospital between December 2015 and April 2019. Factors such as modified Glasgow prognostic score (mGPS), Neutrophil-to-lymphocyte ratio (NLR), and Charlson comorbidity index (CCI) were used to assess immunosenescence. RESULTS: The objective response rate (ORR) and disease control rate (DCR) of all patients were 25.4% (95% confidence interval [CI]: 14.3-39.6) and 52.9% (95% CI: 38.5-67.1), respectively. High mGPS (score of 2) was associated with low DCR compared to low mGPS (score of 0-1) (26.0% vs. 54.0%, p = 0.03). However, none of these scores were significantly related to the ORR. High mGPS was significantly linked to shorter median progression-free survival (mPFS) (4.2 mos. vs. 12.7 mos, p < 0.01), and median overall survival (mOS) (4.8 mos. vs. 28.1 mos, p = 0.03). However, neither CCI nor NLR was associated with prognosis. Multivariate regression analysis identified high mGPS as a significant prognostic factor for mOS (hazard ratio, HR: 0.31 [95% CI: 0.13-0.71], p < 0.01). CONCLUSIONS: High mGPS scores significantly impaired DCR, mPFS, and mOS in patients with advanced NSCLC treated with anti-PD-1 antibodies.

End-of-life impact of concurrent diabetes mellitus and adrenal insufficiency as immune-related adverse events in an advanced non-small cell lung cancer patient.

A 49-year-old man diagnosed with metastatic non-small cell lung cancer was treated with immune checkpoint inhibitor (ICI) combination therapy (nivolumab + ipilimumab) as first-line therapy. During the treatment course, the patient developed ICI-associated diabetes mellitus and adrenal insufficiency, and insulin and hydrocortisone replacement therapy (10 mg/day) were initiated for endocrine toxicity. Despite systemic treatment, the disease progressed. Near the end of the patient's life, he was repeatedly hospitalized for diabetic ketoacidosis and adrenal crisis because he could not physically administer insulin subcutaneously or self-administer oral hydrocortisone due to the deterioration of his general condition as a result of disease progression. This case report demonstrates that it is necessary to evaluate not only the impact of immune-related adverse events on short-term quality of life during ICI treatment but also on the patient's end-of-life care.

Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib.

Introduction: Lorlatinib (LOR) or pemetrexed-based chemotherapy (PEM) is the standard treatment after failure of a second-generation ALK tyrosine kinase inhibitor, such as alectinib, in patients with ALK-positive NSCLC. Nevertheless, there have been few data on the clinical outcomes of these treatments after alectinib failure. Methods: We retrospectively analyzed patients with ALK-rearranged NSCLC who received LOR (LOR group) or PEM (PEM group) as post-treatment after alectinib failure between December 2012 and August 2020. Results: Among 90 patients who experienced disease progression during alectinib treatment, 38 of them received either PEM (n = 22) or LOR (n = 16) as subsequent treatment. The objective response rate and the median progression-free survival were similar in the PEM and LOR groups (objective response rate: 45% versus 44%, p = 0.92; median progression-free survival: 6.9 mo versus 6.2 mo, p = 0.83, respectively). Disease progression during treatment occurred in 22 patients with PEM and 14 patients with LOR. The central nervous system (CNS) was the most common site of progression in both groups. In patients without CNS metastasis at baseline, the cumulative incidence rate of CNS progression was lower over time in the LOR group compared with the PEM group (p = 0.045), whereas in patients with CNS metastasis at baseline, there were no significant differences in cumulative incidence rate of CNS progression between both groups (p = 0.43). Conclusions: Clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC.

Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments.

The balance of programmed death-1 (PD-1)-expressing CD8+ T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) determines the clinical efficacy of PD-1 blockade therapy through the competition of their reactivation. However, factors that determine this balance remain unknown. Here, we show that Treg cells gain higher PD-1 expression than effector T cells in highly glycolytic tumors, including MYC-amplified tumors and liver tumors. Under low-glucose environments via glucose consumption by tumor cells, Treg cells actively absorbed lactic acid (LA) through monocarboxylate transporter 1 (MCT1), promoting NFAT1 translocation into the nucleus, thereby enhancing the expression of PD-1, whereas PD-1 expression by effector T cells was dampened. PD-1 blockade invigorated the PD-1-expressing Treg cells, resulting in treatment failure. We propose that LA in the highly glycolytic TME is an active checkpoint for the function of Treg cells in the TME via upregulation of PD-1 expression.

The Impact of Core Tissues on Successful Next-Generation Sequencing Analysis of Specimens Obtained through Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

The success rate of next-generation sequencing (NGS) with specimens obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) among patients with lung cancer as well as the related clinical factors remain unclear. We aimed to determine the optimal number of punctures and core tissues during EBUS-TBNA for NGS in patients with non-small-cell lung cancer (NSCLC) as well as the association of chest computed tomography (CT) and EBUS findings with successful NGS. We retrospectively reviewed 156 consecutive patients with NSCLC who underwent EBUS-TBNA for NGS (OncomineTM Dx Target Test). Using the receiver operating characteristic curve, we calculated the optimal numbers of punctures and core tissues for NGS and evaluated CT and EBUS findings suggestive of necrosis and vascular pattern within the lesion. The success rate of NGS was 83.3%. The cut-off value for the number of core tissues was 4, and the sensitivity and specificity of successful NGS were 73.8% and 61.5%, respectively. Logistic regression analysis revealed that the number of core tissues (≥4) was the sole predictor of successful NGS. CT and EBUS findings were not associated with successful NGS. Bronchoscopists should obtain sufficient core tissues for successful NGS using EBUS-TBNA specimens.

Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors.

PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene in non-small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare ALK-rearranged tumors. PATIENTS AND METHODS: Between April 2012 and April 2019, clinical outcomes and characteristics of patients with ALK-rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression. RESULTS: We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. CONCLUSION: This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

Feasibility of next-generation sequencing (Oncomine™ DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients.

BACKGROUND: The Oncomine™ Dx Target Test based on next-generation sequencing has been approved for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. METHODS: We assessed the tissue sample factors that affect the success rate of Oncomine™ Dx Target Test companion diagnostics and the feasibility of using biopsy specimens for Oncomine™ Dx Target Test companion diagnostics in advanced non-small-cell lung cancer patients. RESULTS: Ninety-nine biopsy samples were subjected to genetic testing using the Oncomine™ Dx Target Test companion diagnostics to detect v-raf murine sarcoma viral oncogene homologue B1 mutations (Cohort 1), and 136 biopsy samples were examined using Oncomine™ Dx Target Test companion diagnostics for the detection of multiple oncogenic mutations (Cohort 2) between July 2018 and April 2020. We retrospectively collected clinical and pathological data, including tissue size and tumour cell content. The success rate was 77% (76/99) in Cohort 1 and 93% (127/136) in Cohort 2. In Cohort 1, the success rate was significantly associated with the tumour cell content: the success rate was 63% for samples with a tumour cell content of <20%, whereas it was 83% for samples with a tumour cell content of 20% or higher (P = 0.0446). The tissue size also affected the success rate: a success rate of 57% was obtained for tissue sizes <4 mm2, whereas a success rate of 95% was obtained for tissue sizes of 4 mm2 or larger (P < 0.0001). In Cohort 2, the success rate was 100% when tumour specimens with a tissue size of 4 mm2 or larger were used. CONCLUSIONS: Tissue size and tumour cell content were significantly associated with the success rate of Oncomine™ Dx Target Test companion diagnostics.

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC.

BACKGROUND: Pembrolizumab has shown significantly better efficacy than platinum doublet chemotherapy in patients with programmed cell death ligand 1 (PD-L1) strongly positive (tumor proportion score ≥ 50%) non-small-cell lung cancer (NSCLC). However, the predictors of response to pembrolizumab have not yet been fully elucidated for patients with PD-L1 strongly positive NSCLC. PATIENTS AND METHODS: We retrospectively analyzed 145 patients who had been treated with pembrolizumab for PD-L1 strongly positive (TPS ≥ 50%) NSCLC without an EGFR (epidermal growth factor receptor) mutation or ALK rearrangement from February 2017 to March 2020. Various clinical characteristics, including Eastern Cooperative Oncology Group performance status, treatment line, PD-L1 expression, C-reactive protein level, neutrophil/lymphocyte ratio, and metastatic sites, and the clinical outcome of pembrolizumab treatment were examined. RESULTS: Patients with higher PD-L1 expression (≥ 75%; n = 90) had a higher objective response rate (ORR) and longer progression-free survival (PFS) compared with those with lower expression (50%-74%; n = 55; ORR, 51% vs. 33%; P = .0305; median PFS, 13.9 months vs. 5.2 months; P = .0111). In addition, 15 patients with liver metastasis (LM) had a significantly lower ORR and shorter PFS than the 130 patients without LM (ORR, 20% vs. 47%; P = .0468; median PFS, 3.4 months vs. 9.4 months; P = .0018). A multivariate analysis indicated that PD-L1 expression and LM were significant predictors of PFS after pembrolizumab treatment (higher PD-L1 expression: hazard ratio, 0.58; 95% confidence interval, 0.38-0.91; P = .0183; presence of LM: hazard ratio, 2.05; 95% confidence interval, 1.03-3.82; P = .0420). CONCLUSION: PD-L1 expression and LM status were predictors of the efficacy of pembrolizumab in patients with PD-L1 strongly positive NSCLC.

Comparative study of programmed cell death ligand-1 immunohistochemistry assays using 22C3 and 28-8 antibodies for non-small cell lung cancer: Analysis of 420 surgical specimens from Japanese patients.

OBJECTIVES: Multiple programmed cell death ligand-1 (PD-L1) immunohistochemistry assays are currently used as companion or complementary diagnostic tools for anti-programmed cell death-1 immunotherapies. We aimed to characterize two PD-L1 immunohistochemistry assays (Dako 22C3 and 28-8) for non-small cell lung cancer (NSCLC) in clinical laboratories. MATERIALS AND METHODS: Surgical specimens from 420 patients with pathological stages IA to IIIA NSCLC were investigated. The archived samples were freshly cut into 5-µm-thick sections stained with antibodies 22C3 and 28-8, and tumoral PD-L1 expression was evaluated in two clinical laboratories, respectively. Overall, positive, and negative percent agreement (OPA, PPA, and NPA, respectively) at specified PD-L1 cutoffs were calculated to assess the concordance between 22C3 and 28-8 assays. RESULTS: Tumoral PD-L1 expression of ≥ 1% was detected by either 22C3 or 28-8 assays in 176 cases (41.9%), whereas 22C3 revealed a significantly higher tumoral PD-L1 expression compared to 28-8 (median 30% vs. 10%, p < 0.0001). OPA was 89.0, 90.2, and 91.9% at 1, 25, and 50% cutoff levels. When 22C3 was compared to a standard assay 28-8, the PPA was 85.5, 98.3, and 94.9%, whereas NPA was 91.0, 89.0, and 91.6% at 1, 25, and 50%. On the other hand, when 28-8 was compared to 22C3, PPA was 84.4% at 1%, but it decreased to 58.3 and 53.6% at 25 and 50%; whereas NPA remained high (91.7, 99.7, and 99.4% at 1, 25 and 50%, respectively). CONCLUSION: Our analysis revealed that, despite the high OPA, there was discordance in the PPA between 22C3 as a standard assay and 28-8 as a comparator assay at 25% and 50% PD-L1 cutoff levels, indicating that the results of 28-8 could be translated to those of 22C3 but not vice versa.

Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with advanced non-small-cell lung cancer treated with nivolumab.

BACKGROUND: There is an unmet need to identify markers that predict the response to nivolumab in patients with non-small-cell lung cancer (NSCLC). The neutrophil-to-lymphocyte ratio (NLR) was recently recognized as an indicator of a poor prognosis in patients with various cancers. In the present study, we quantified the predictive impact of NLR in patients with NSCLC treated with nivolumab. METHODS: We retrospectively analyzed 101 patients with advanced NSCLC treated with nivolumab at Kansai Medical University Hospital from December 2015 to December 2016. Patients were administered nivolumab at a dose of 3 mg/kg every 2 weeks. The predictive value of NLR for disease progression before treatment and 2 and 4 weeks after nivolumab treatment was assessed. RESULTS: The median progression-free survival (PFS) of patients with an NLR of < 3 before treatment was 3.4 months, whereas that of patients with an NLR of ≥ 3 was 2.9 months (p = 0.484). The median PFS of patients with an NLR of < 3 at 2 weeks after treatment was 5.3 months, whereas that of patients with an NLR of ≥ 3 was 2.1 months (p = 0.00528). The median PFS of patients with an NLR of < 3 at 4 weeks after treatment was 5.3 months, whereas that of patients with an NLR of ≥ 3 was 2.0 months (p = 0.00515). CONCLUSION: The NLR at 2 and 4 weeks after treatment might be a useful marker for the prediction of the treatment response or disease progression in patients with advanced NSCLC receiving nivolumab.

Tyrosine kinase inhibitor and rituximab-CHOP treatment for concurrent chronic myeloid leukemia and non-Hodgkin lymphoma: a case report.

Non-Hodgkin lymphoma can occur concurrently with chronic phase-chronic myeloid leukemia (CML) at initial diagnosis. Combination treatment with second-generation tyrosine kinase inhibitors and rituximab-CHOP for patients newly diagnosed with CML and non-Hodgkin lymphoma is effective for both diseases. However, we found that this treatment combination may induce severe myelosuppression.

Retrospective analysis of single-agent nab-paclitaxel in patients with platinum-resistant non-small cell lung cancer.

A retrospective study was conducted to investigate the efficacy and toxicity of single-agent nab-paclitaxel in 67 patients with platinum-resistant non-small cell lung cancer in Kansai Medical University Hospital from August 2013 to December 2015. Overall, 25% of patients experienced disease progression, 48% exhibited a partial response, 27% had stable disease and 0% had a complete response. The median progression-free survival (PFS) time was 4.8 months and the median overall survival time was 18.2 months. There was no statistically significant difference in PFS between patients with non-squamous carcinoma and squamous carcinoma, or between second-line use and post-second-line use. The most common severe adverse event was neutropenia, followed by interstitial lung disease, infection and fatigue. The results revealed that single agent nab-paclitaxel was associated with an acceptable level of toxicity and a favorable response. This regimen has been developed recently, thus it has not been sufficiently evaluated its toxicity and efficacy. Additional studies to evaluate these parameters in non-small cell lung cancer are warranted.

Interstitial Lung Disease Following Single-Agent Nanoparticle Albumin-Bound Paclitaxel Treatment in Patients with Advanced Non-Small Cell Lung Cancer.

Interstitial lung disease (ILD) is a serious and potentially fatal adverse event in lung cancer therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel, solvent-free formulation of paclitaxel (PTX). Although the incidence of nab-PTX-induced ILD is not clear, it is generally considered that this formulation presents a similar risk of developing ILD as PTX. Here, we report 3 patients who developed severe ILD following treatment with nab-PTX. We draw attention to the risk of developing drug-induced ILD following nab-PTX treatment, and highlight that this novel formulation might therefore not be as safe as PTX with respect to the development of ILD.

Phase I/II study of erlotinib, carboplatin, pemetrexed, and bevacizumab in chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer harboring epidermal growth factor receptor mutation.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors significantly prolong the progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth and their prognosis remains poor. A new treatment strategy for NSCLC harboring EGFR mutation is therefore necessary. METHODS: In phase I, eligible patients were administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and bevacizumab until progressive disease was observed. The dose of erlotinib was 100 mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed, carboplatin, and bevacizumab were fixed at 500 mg/m2, area under the concentration-time curve of 6 mg/mL · min, and 15 mg/kg, respectively. The dose-limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4 leukopenia lasting for ≥7 days, grade 4 thrombocytopenia, grade 3/4 uncontrollable nonhematological toxicity, and delayed administration of the subsequent cycle by >2 weeks because of adverse events. RESULTS: Six patients were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the induction phase, grade 3 neutropenia without fever was observed in one patient at dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients at dose level 1 and dose level 2, respectively. CONCLUSION: Four-drug combination therapy is a feasible and promising.