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Background Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy. Whether adding a neurokinin-1 receptor antagonist to a first-generation 5HT3 antagonist (1st-5HT3RA) and dexamethasone (DEX) is beneficial in patients on L-OHP-based chemotherapy is controversial. It is unclear whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV. We, therefore, investigated whether PALO+DEX (PALO group) or 1st-5HT3RA+DEX+APR (APR group) was more effective in controlling delayed CINV, as well as risk factors for delayed CINV, in patients with CRC treated with L-OHP-based chemotherapy. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial and compared the incidence of CINV between the PALO and APR groups using propensity score-matched analysis. Risk factors for CINV were identified using logistic regression models. Results Among the 404 eligible patients, those in the PALO group showed a higher incidence of delayed CINV than those in the APR group (nausea: 43.4% vs. 32.4%, P = 0.061; vomiting: 12.5% vs. 4.4%, P = 0.017). The logistic regression analysis identified alcohol consumption, motion sickness, and PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and PALO+DEX regimen as those for delayed vomiting. Conclusions Treatment with the three antiemetics, including APR, was more effective in controlling delayed CINV than prophylactic treatment with the two antiemetics, including PALO. Thus, patients with CRC receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Nrf2 is a transcription factor associated with cancer growth and chemotherapy resistance. Nrf2 expression levels may be associated with prognosis of lung cancer, but previous results have been inconsistent. Methods The expression of Nrf2 in 1037 surgically resected lung adenocarcinoma (LAD) specimens was evaluated by immunohistochemistry. Nrf2 positivity was defined based on the intensity of stained nucleus of tumor cells on the tissue microarray: negative, weakly positive and strongly positive. The correlations between the Nrf2 expression and the prognosis, clinicopathological features and driver oncogene alterations were analyzed. Results The Nrf2 expression was negative in 236 (23%) of 1037 tumors, weakly positive in 444 (43%) and strongly positive in 357 (34%). The proportion of Nrf2-positive tumors was significantly higher in patients with pathological stage I (81%), tumors with EGFR mutations (87%) or KRAS mutations (87%), tumors without ALK fusions (78%) or ROS1 fusions (78%). The Nrf2 expression was not associated with the age, gender and smoking status. In multivariate analysis (Logistic regression model), pathological stage I, positive EGFR or KRAS mutation status were significant predictors of Nrf2 positivity. The increased expression of Nrf2 was associated with longer overall survival regardless of driver oncogene status. In multivariate analysis (Cox proportional hazards model), advanced age, male gender, advanced pathological stage and negative EGFR mutation status were significant unfavorable prognostic factors. Conclusions LADs that positively express Nrf2 have unique clinicopathological features. The increased expression of Nrf2 is a favorable prognostic marker in surgically resected LAD. Legal entity responsible for the study The authors. Funding AMED. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan–Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors. • Acral melanoma is a distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. • We retrospectively examined advanced-stage acral melanoma patients treated with an anti-PD-1 antibody. • Anti-PD-1 antibodies have limited efficacy in Japanese acral melanoma patients. • Patients with nail apparatus melanoma had poorer response and survival than patients with palm and sole melanoma. [ABSTRACT FROM AUTHOR]

Background The emetogenic classification of antineoplastic agents has provided a framework for defining antiemetic treatment recommendations in international guidelines. The most widely used classification schema identified four emetic risk levels. However, information on the emetogenicity of each chemotherapeutic regimen is insufficient. We previously reported that the emetic risk of pemetrexed was higher than that of taxans. Risk factors for chemotherapy-induced nausea and vomiting (CINV) were also assessed in patients with lung cancer receiving carboplatin plus pemetrexed (CBDCA+PTX) or carboplatin plus paclitaxel (CBDCA+PEM), and the CINV incidence was compared between these two regimens. Methods Data were pooled from two prospective studies, and propensity score matching was used to compare the CINV incidence between CBDCA+PTX and CBDCA+PEM groups. Risk factors for CINV were identified using logistic regression models. The pattern of CINV occurrence was evaluated by 7-day patient diary for recording CINV after the commencement of chemotherapy. Results Among 240 evaluable patients, the CINV incidence was higher in the CBDCA+PEM group than in the CBDCA+PTX group at the delayed phase (nausea: 51.1% vs. 36.2%, P = 0.040; vomiting: 23.4% vs. 14.9%, P = 0.138). The pattern of delayed CINV occurrence peaked on days 5 and 4 for CBDCA+PEM and CBDCA+PTX regimens, respectively. Logistic regression analysis identified younger age, female sex, no alcohol consumption, two antiemetics, and CBDCA+PEM regimen as independent risk factors associated with delayed nausea, and female sex and two antiemetics for delayed vomiting. Conclusions The emetic risk of CDBCA+PEM regimen was higher than that of CBDCA+PTX regimen. More aggressive antiemetic prophylaxis such as quadruple therapy, including olanzapine, may be considered in patients receiving CDBCA+PEM regimen. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). Patients and methods: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m² or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). Results: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). Conclusion: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal stromal tumor (GIST) is a type of mesenchymal tumor and has KIT mutations in 80–90% of the cases. The development of tyrosine kinase inhibitors have greatly improved patient outcomes. We have previously described association between lower pfetin (KCTD12) expression and poor prognosis in the GIST patients (Ref 1. Suenara Y et al. Clin Cancer Res2008). In this study, to investigate the protein profiles of kit expression, we performed comprehensive protein expression analysis using the gastric tumor cell lines and surgical specimens in GIST. Methods We performed KITgene knockdown using siRNA inthe GIST cell line (T1 cell line) and generated the protein expression profiling data by i-TRAQ. Based on this i-TRAQ protein profiling data from the T1 cell line, we referenced our previously published protein expression analysis databases associated with GIST prognosis in the patient samples (Ref 1.) and compared the protein profile of KIT-associated proteins (T1 cell line) and prognosis-associated protein (patient samples). Results In our study, the i-TRAQ profiling method detected expression of approximately 1500–2000 proteins. In KITknockdown cells, 125 proteins were identified to have statistically different expression (p < 0.05). Based on our previously published GIST prognosis protein profile database (using 17 patient tissue samples), 25 proteins were identified to be statistically significant (p < 0.05). Upon comparing the prognosis database with theKIT knockdown database, 6 proteins were identified as common proteins.In particular, the heat shock protein (HSP) 90-beta, which has been previously shown to contribute to the growth of cancer cells, was identified as a critical protein in the biological behavior of GIST. Conclusions HSP 90-beta is currently considered as a therapeutic target for HSP 90 inhibitors against imatinib-resistant GIST. Our data suggests that the differentiation and cell growth of GIST may be enhanced by the identified proteins, which are in turn induced by KIT. We believe that our established protein profile data will help in improving the understanding of malignant behaviors in GIST. Clinical trial identification HSP 90-betaplay an important role in the tumor progression of GISTs. Legal entity responsible for the study Juntendo University. Funding This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19K22694, #19H03789 and #15KK0353 to Y.S. ; #17K08730 to T.S.; #17K10987to K.K.; #19K16753 to K.A.; #18K15329 to T.O. , # 18K16634 to Y.K.) and Leading Advanced Projects for Medical Innovation (LEAP) (Grant Number # JP18am0001009) and the Practical Research for Innovative Cancer Control (Grant Number # JP18ck0106252) from the Japan Agency for Medical Research and Development. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Chemotherapy-induced neutropenia (CIN) is a dose-limiting toxicity of many chemotherapy agents. Recently, CIN has been associated with longer survival time in various types of cancer, suggesting a role as a prognostic factor. However, no large-scale study has yet investigated the utility of CIN as a prognostic factor in small cell lung cancer. We therefore conducted this multicenter retrospective observational study to investigate the utility of CIN as a prognostic factor for overall survival (OS) in patients with extensive-disease small-cell lung cancer (ED-SCLC) treated with chemotherapy. Methods Clinical data, including data on CIN onset during chemotherapy, were collected from electronic medical records of patients with ED-SCLC who received standard-dose irinotecan and cisplatin (IP regimen) as primary therapy at 14 participating institutions across Japan between January 1, 2012 and December 31, 2016. Landmark analysis, with the association between OS and neutropenia as the primary endpoint was performed with 102 patients who completed all four cycles of the IP regimen and whose OS was ≥112 days. Univariate analysis using the log-rank test and multivariate analysis using the Cox proportional hazards model with factors previously identified as possible prognostic factors as covariates were also performed to examine the association between CIN and OS. Results Analysis of median OS by grade among patients who developed CIN revealed significantly longer survival in the group with grade 4 CIN (633 days, 95% confidence interval [CI]: 379–757) than in the group with grade 0 to 3 CIN (444 days, 95% CI: 360–505) (P = 0.0279). Multivariate analysis suggested that lactate dehydrogenase (LDH) of ≥ 230 IU/L (hazard ratio [HR]: 2.937; 95% CI: 1.739–4.958, P < 0.001) and grade 0 to 3 CIN (HR: 2.096; 95% CI: 1.151–3.818, P = 0.0156) are independent poor prognostic factors for ED-SCLC. Conclusions Onset of grade 4 CIN was associated with longer OS in patients with ED-SCLC. Our results also show that both LDH and CIN may be prognostic factors in patients treated using the IP regimen. Clinical trial identification This study was approved by the Institutional Review Board of our institution (approval no: T29-8-30-2-3). Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]