Glasgow prognostic score predicts efficacy and prognosis in patients with advanced non-small cell lung cancer receiving EGFR-TKI treatment.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations, some patients experience little or no response. The Glasgow prognostic score (GPS) is an inflammation-related score based on C-reactive protein (CRP) and albumin concentrations, and has prognostic value in various cancer settings. This study aimed to evaluate whether GPS could predict response of NSCLC to EGFR-TKIs. METHODS: This retrospective multicenter study evaluated patients with NSCLC harboring EGFR mutations who received EGFR-TKI monotherapy from October 2006 to December 2016. GPS values were determined using CRP and albumin concentrations from before initiation of EGFR-TKIs. The Kaplan-Meier method and Cox proportional hazard models were used to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: In 214 patients, 141, 43, and two patients had GPS values of 0, 1, and 2, respectively. The GPS independently predicted the efficacy of EGFR-TKIs; good GPS (0-1) conferred significantly better PFS (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.38-0.96, P = 0.03) and OS (HR: 0.56, 95% CI: 0.33-0.96, P = 0.03). Multivariate analysis confirmed that a good GPS (0-1) independently predicted good PFS and OS among patients who had PS of 0-1. Good GPS (0-1) independently predicted good OS among patients receiving treatment in first-line settings. CONCLUSIONS: The GPS independently predicted the efficacy of EGFR-TKIs for EGFR-mutated NSCLC; however, further studies are needed to validate our findings. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Glasgow prognostic score (GPS) independently predicted the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutated NSCLC. WHAT THIS STUDY ADDS: The findings presented in this paper will help to identify patients who will be expected to experience limited or no response to EGFR-TKI treatment by using GPS.

Administration of docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte colony-stimulating factor for pretreated non-small cell lung cancer: a phase II study.

PURPOSE: Although docetaxel plus ramucirumab has shown superior treatment efficacy over docetaxel monotherapy for patients with non-small cell lung cancer (NSCLC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to validate the primary prophylactic use of pegfilgrastim with docetaxel and ramucirumab treatment in Japanese patients with NSCLC. METHODS: Patients with NSCLC with progression after at least one round of chemotherapy were enrolled and administered docetaxel (60 mg/m2) plus ramucirumab (10 mg/kg) intravenously on day 1, followed by pegylated-granulocyte colony-stimulating factor (3.6 mg) on day 2 of a 21-day treatment cycle. The primary study endpoint was the percentage of patients who developed FN. Secondary endpoints included overall survival, progression-free survival, overall response rate, and safety. RESULTS: Overall, 20 patients (15 men and 5 women) were enrolled, of whom one developed FN, resulting in an overall FN rate of 5%. The response and disease control rates were 40% and 85%, respectively. The median progression-free survival was 6.6 (95% confidence interval [CI], 0.5-NR) months. The median overall survival was 18.4 (95% CI, 2.2-11.0) months. Six patients aged over 75 years were included in this study, and although most adverse events were durable, ramucirumab-associated adverse events occurred more frequently in these patients. CONCLUSIONS: We observed a 5% FN rate using primary prophylactic pegylated-granulocyte colony-stimulating factor with docetaxel plus ramucirumab in Japanese patients with NSCLC. While most adverse events were durable, elderly patients should be closely monitored.

An Exploratory Randomized Phase II Trial Comparing CDDP Plus S-1 With Bevacizumab and CDDP Plus Pemetrexed With Bevacizumab Against Patients With Advanced Non-squamous Non-small Cell Lung Cancer.

BACKGROUND/AIM: It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naïve patients received S-1 (80 mg/m2) from day 1 to day 14 plus cisplatin (80 mg/m2) on day 1 with bevacizumab (15 mg/kg) on day 1, followed by maintenance with bevacizumab plus S-1 (SCB) on day 1 every 3 weeks and pemetrexed (500 mg/m2) on day 1 plus cisplatin (75 mg/m2) on day 1 with bevacizumab (15 mg/kg) on day 1 followed by maintenance bevacizumab plus pemetrexed (PCB) on day 1 every 3 weeks. The expression of thymidylate synthase (TS) was analyzed using immunohistochemistry. RESULTS: Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS. CONCLUSION: The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC.

Dual inhibition of MEK and p38 impairs tumor growth in KRAS-mutated non-small cell lung cancer.

Despite the high frequency of KRAS mutations in non-small cell lung cancer (NSCLC), therapeutic modalities targeting KRAS-mutated NSCLC have not been established. Based on our previous findings that mutant KRAS knockdown sensitized NSCLC cells to a p38 inhibitor, the growth-inhibitory effect of dual MEK and p38 inhibition on tumor growth in NSCLC cells harboring KRAS mutations was investigated. In KRAS-mutated NSCLC cells, the MEK inhibitor, selumetinib, inhibited cell growth in a dose-dependent manner, and its growth-inhibitory effect was enhanced by combined treatment with the p38 inhibitor LY2228820. Similarly, another pair of MEK and p38 inhibitors also exhibited antitumor activity. Small interfering RNAs (siRNAs) against MAPK14, which encodes p38α MAPK, enhanced the growth-inhibitory effect of the MEK inhibitors in NSCLC cells with KRAS mutations. Notably, MEK inhibitors reduced p38 expression levels but increased p38 phosphorylation levels, resulting in sensitization to p38 inhibitors in KRAS-mutated NSCLC cells. These results provide evidence that dual MEK and p38 inhibition could be a potent therapeutic strategy against oncogenic KRAS-driven NSCLC.

Post-treatment Glasgow Prognostic Score Predicts Efficacy in Advanced Non-small-cell Lung Cancer Treated With Anti-PD1.

BACKGROUND/AIM: No definitive biomarker exists for predicting treatment efficacy or response to therapy with antibody to programmed cell death-1 (PD1) for patients with advanced non-small cell lung cancer (NSCLC). Hence, we investigated whether the Glasgow prognostic score (GPS) predicted anti-PD1 treatment response for advanced NSCLC. PATIENTS AND METHODS: This study retrospectively identified 47 patients with NSCLC treated with anti-PD1 and assessed the prognostic value of the GPS. The GPS was calculated using C-reactive protein and albumin concentrations 1 month after starting anti-PD1 treatment. Kaplan-Meier method and Cox proportional hazard models were used to examine differences in progression-free (PFS) and overall (OS) survival, and clinical response. RESULTS: The post-treatment GPS independently predicted anti-PD1 treatment efficacy, as a good post-treatment GPS (GPS 0-1) was significantly associated with improved PFS. Intra-treatment GPS change was associated with clinical response. CONCLUSION: The post-treatment GPS independently predicted efficacy of anti-PD1 treatment for NSCLC.

Small Cell Lung Cancer with Sarcoidosis in Spontaneous Remission: A Case Report.

A 69-year-old woman was diagnosed with sarcoidosis, which was not treated with corticosteroid therapy. Her levels of angiotensin converting enzyme decreased significantly over 4 years and a mass lesion was detected near the lower part of her left main bronchus, and diagnosed as small cell lung cancer (SCLC). Treatment of the SCLC with a series of chemotherapeutic agents produced excellent results. The pulmonary sarcoidosis did not show any deterioration despite the frequent use of amrubicin, which is known to be a cause of interstitial pneumonia. This is a case report of SCLC complicated with sarcoidosis in a stage of spontaneous remission, possibly suggesting an association between sarcoidosis and tumor immunity, since recent reports have suggested that immune checkpoint inhibitors might be involved in the development of sarcoidosis.

The Onset of Eosinophilic Pneumonia Preceding Anti-synthetase Syndrome.

A 66-year-old man had been treated with prednisolone for eosinophilic pneumonia for 8 years. His slowly progressing cough and dyspnea were accompanied by elevated levels of fibrotic serological markers and an increased reticular shadow on chest computed tomography images. The patient had recently tested positive for anti-EJ antibodies, a type of anti-aminoacyl-tRNA synthetase antibody; therefore, we diagnosed him with an exacerbation of interstitial pneumonia due to anti-synthetase syndrome (ASS). He was treated with tacrolimus and an increased prednisolone dosage. We herein present the first reported case of eosinophilic pneumonia preceding anti-EJ antibody-positive ASS.

Isoniazid-induced Pure Red Cell Aplasia in a Patient with Sarcoidosis: A Patient Summary and Review of the Literature.

A 41-year-old woman treated with isoniazid (INH) for latent tuberculosis infection and an oral corticosteroid for sarcoidosis developed severe anemia two months after initiating INH. A bone marrow examination showed erythroblastopenia, and a diagnosis of INH-induced pure red cell aplasia (PRCA) was made. Her reticulocyte count and hemoglobin levels improved two weeks after discontinuation of INH. A literature review of INH-induced PRCA shows that it occurs very rarely in the context of autoimmune disorders. This report describes a case of INH-induced PRCA occurring in a patient with sarcoidosis.

An Autopsy Case of Fulminant Hepatitis in a Patient with Multiple Sclerosis Treated by Interferon-Beta-1a.

A 44-year-old woman with multiple sclerosis (MS) receiving interferon (IFN)-beta-1a treatment was admitted to a local hospital for severe icterus and liver injury. She was transferred to our university hospital because fulminant hepatitis (FH) was suspected. She was diagnosed with acute-type FH based on hepatic coma, severe liver injury and liver failure, and she received plasma exchange and continuous hemodiafiltration therapy. On hospital day 6, she died from liver failure despite intensive care. An autopsy revealed histological findings consistent with FH. Physicians should monitor the hepatic function of MS patients receiving IFN-beta-1a treatment, as serious events can occur in rare cases.