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Background Cancer-related fatigue is one of the most common and persistent issues experienced by cancer patients. Cancer-related fatigue is a distinct form of fatigue that is subjective, long-lasting and unalleviated by rest or sleep. Studies have shown that almost all cancer patients experience severe fatigue that disrupts the quality of life and physical function, but cancer-related fatigue remains under-addressed in clinical care, and only about half of all patients receive treatment. Methods To increase the awareness of cancer-related fatigue and improve current management, the Taiwan Society of Cancer Palliative Medicine and the Taiwan Oncology Nursing Society convened a consensus committee to develop recommendations for the screening, assessment and treatment of cancer-related fatigue. Results Thirteen consensus recommendations were subsequently developed based on the best available evidence and the clinical experience of committee members. Conclusions These recommendations are expected to facilitate the standardization of cancer-related fatigue management across Taiwan and may also serve as a reference for other clinicians.

Background This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP). Results In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26–0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ≥3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib. Conclusions Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression. Trial registration ClinicalTrials.gov NCT01988493.

Advanced breast cancer (ABC) has become a chronic disease. In such a situation, an effective therapy with low toxicities and economically acceptable is needed. Metronomic vinorelbine (mVNR) has been proved to be effective on the control of MBC. The aim of this study is to evaluate the efficacy and safety of mVNR as the salvage therapy for patients with ABC. Oral vinorelbine (VNR) was administered at 70 mg/m2, fractionated on days 1, 3, and 5, for 3 weeks on and 1 week off. Once the mVNR was combined with trastuzumab, or was combined with bevacizumab, the schedule was changed to 2 weeks on and 1 week off. Clinical data of patients with ABC who had received treatment with mVNR and tumor characteristics were collected and analyzed. From Mar. 2013 to Dec, 2020, there were 90 patients with ABC received mVNR. The overall response rate was 53.3% and overall disease control rate (DCR) was 78.9% in this study, including 4 (4.4%) cases reached complete response, 44 (48.9%) cases reached partial response and 23 (25.6%) cases were table disease. The median time to treatment failure (TTF) of the Lumina A patients was 13.3 months, Lumina B patients was 9.1 months, Her-2 enrich patients was 8.9 months, and triple negative breast cancer (TNBC) patients was 5.6 months. Median overall survival time for Lumina A, Lumina B, Her-2 enrich and TNBC were 54.6 months, 53.3 months, 59.5 months and 24.5 months separately. Side effects were minimal and manageable. Metronomic VNR can be an effective treatment for ABC either works as a switch maintenance or salvage therapy. In combination with target therapy or hormonal therapy, mVNR can further improve TTF and DCR with minimal toxicities. Further study should focus on the optimal dosage, schedule and combination regimen.

Background Cancer-related fatigue (CRF) is an emerging clinical issue, although its prevalence and impact on quality of life (QOL) in cancer patients in Taiwan remain unclear. The present nationwide cross-sectional study was conducted to provide a thorough overview of the prevalence, related factors and impact of CRF in Taiwan. Methods In this multi-center survey, data were collected using the International Classification of Diseases 10th Revision (ICD-10) Fatigue evaluation, Brief Fatigue Inventory–Taiwan (BFI-T), the Chinese version of the Symptom Distressed Scale and a fatigue experience survey. Logistic regression was used to determine the correlations between fatigue characteristics and the factors studied. Results A total of 1207 cancer patients were recruited from 23 hospitals in Taiwan. Fatigue was the most distressing symptom in Taiwanese cancer patients. The distress score was higher if CRF was diagnosed using ICD-10 compared with BFI-T. Rest and nutritional supplementation were the most common non-pharmacological treatments; blood transfusion was the most common pharmacological treatment. There were 45% of patients reported not receiving a timely intervention for fatigue. Conclusions Fatigue is the most bothersome symptom reported by Taiwanese cancer patients. Caregivers should be aware of the impact of CRF on QOL in cancer patients, constantly measure the severity of fatigue and provide appropriate interventions., Depending on the questionnaire used, the prevalence of fatigue in cancer patients in Taiwan ranges from 23.4 to 71.9%. Fatigue is the most bothersome symptom reported by cancer patients.

BackgroundThere are no randomized control trials comparing the efficacy of trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC). Herein, we conducted an observational study to compare the oncologic outcomes of trifluridine/tipiracil-containing regimen (TAS-102) and regorafenib-containing regimen (REG) in patients with mCRC.Material and methodPatients who were diagnosed to have mCRC in 2015 to 2021 and treated with TAS-102-containing regimen or REG-containing regimen were recruited. Monotherapy or combination therapy were all allowed in this study. Oncologic outcomes were presented with progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR).ResultsA total of 125 patients were enrolled into our study, accounting for 50 patients with TAS-102 and 75 patients with REG. Of these patients, 64% were treated with TAS-102 or REG monotherapy, while the remaining were treated with TAS-102 combination or REG combination. In general, the median PFS and OS were 3.7 versus 2.0 months (P = 0.006) and 9.2 versus 6.8 months (P = 0.048) in TAS-102 and REG, respectively. The ORR and DCR were 44% versus 20% (P < 0.001) and 72% versus 43% (P < 0.001) in TAS-102 and REG, respectively. As for treatment strategies, the survival were significantly longer in combination than in monotherapy, no matter in TAS-102 or REG group. Multivariate analysis showed TAS-102 and combination therapy were independent predictor associated with better survival.ConclusionsOur results suggested that TAS-102 had better oncologic outcomes than REG in patients with mCRC, especially in combination. Further prospective trials are warranted to confirm our results.

550 Background: TOPAZ-1 (NCT03875235) is a double-blind, Phase 3 study of durvalumab (D), an immune checkpoint inhibitor (ICI), + gemcitabine and cisplatin (GC) in participants (pts) with advanced biliary tract cancer (BTC). D + GC improved overall survival (OS) in pts with advanced BTC versus placebo (PBO) + GC (Oh et al. NEJM Evid 2022). Use of antibiotics during ICI treatment has been correlated with poorer OS and progression-free survival (PFS; Jiang et al. Front Oncol 2022). Methods: Pts were randomized 1:1 to receive D (1500 mg) or PBO on Day 1 every 3 weeks (Q3W), + G (1000 mg/m2) and C (25 mg/m2) on Days 1 and 8 Q3W, for ≤8 cycles, followed by D or PBO monotherapy Q4W. This exploratory subgroup analysis of TOPAZ-1 assessed OS and PFS by systemic antibiotic use during the study (≥1 dose 14 days before first D/PBO dose to 14 days after last D/PBO dose). Hazard ratios (HRs) were estimated using an unstratified Cox proportional hazards model, adjusting for disease status (initially unresectable or recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer). Data cut-off at primary analysis was Aug 11, 2021. Results: The number (%) of pts using antibiotics during the study (D + GC, 167/341 [49.0%]; PBO + GC, 167/344 [48.5%]) was similar between treatment arms. In the D + GC arm, median OS (95% CI) was similar regardless of antibiotics use: 12.6 (9.7–14.8) months in pts with antibiotics use vs 13.0 (10.8–14.7) months in pts without (Table). In the PBO + GC arm, median OS (95% CI) was 10.3 (8.7–12.5) in pts with antibiotics use vs 12.1 (11.0–13.8) in pts without. OS HRs (95% CI) in D + GC vs PBO + GC were 0.78 (0.59–1.02) in pts with antibiotics and 0.81 (0.62–1.07) in pts without. Median PFS (95% CI) was 7.3 (6.5–7.7) months in pts with antibiotics use vs 7.2 (5.9–7.4) months in pts without in the D + GC arm and 5.7 (5.4–6.6) months vs 6.1 (5.6–7.3) months, respectively, in the PBO + GC arm (Table). PFS HRs (95% CI) were 0.70 (0.55–0.89) in pts with antibiotics use and 0.82 (0.65–1.03) in pts without. Conclusions: In the TOPAZ-1 study of D in BTC, no meaningful difference was found in OS or PFS for participants who received antibiotics during the study period compared with those who did not, and results were consistent with the primary analysis. These results support that people receiving D may be treated with antibiotics when clinically indicated. Clinical trial information: NCT03875235 . [Table: see text]

The global, randomized NAPOLI‐1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal‐IRI) plus 5‐fluorouracil/leucovorin (nal‐IRI+5‐FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine‐based therapy. Median overall survival (OS) with nal‐IRI+5‐FU/LV was 6.1 vs 4.2 months with 5‐FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post‐hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal‐IRI+5‐FU/LV (n = 34) had significantly longer median OS versus 5‐FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal‐IRI+5‐FU/LV versus 5‐FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal‐IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5‐FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal‐IRI+5‐FU/LV versus 5‐FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal‐IRI+5‐FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine‐based therapy, with a safety profile agreeing with previous findings. The nal‐IRI+5‐FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506), The global NAPOLI‐1 phase 3 trial (NCT01494506) evaluated the safety and efficacy of liposomal irinotecan (nal‐IRI) and 5‐fluorouracil/leucovorin (5‐FU/LV) compared with 5‐FU/LV in patients with metastatic pancreatic adenocarcinoma that progressed following gemcitabine‐based therapy. We report data from a post‐hoc subgroup analysis focusing on Asian patients at centers in South Korea and Taiwan. Our findings are consistent with those from the primary analysis and show that, despite association with higher incidence of manageable grade 3‐4 neutropenia, the nal‐IRI+5‐FU/LV regimen is an effective treatment option in Asian patients with gemcitabine‐failed metastatic pancreatic cancer.

Objectives: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. Methods: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. Results: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84–5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11–3.65, p = 0.02) were independent prognostic factors. Conclusion: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.

Simple Summary Systemic therapies for advanced biliarty tract cancers (BTC) are limited. The combination of gemcitabine with cisplatin (GC) has been the standard first-line treatment for advanced BTC from 2010 until now. In order to improve therapeutic effect, especially response rate, we added a novel schedule and dosage of bevacizumab to standard GC regimen. In our real world date, we found this regimen could increase the overall response rate to 50.0%, and side effects were managable. For patients with advanced BTC, especially whose tumors need rapid response to treatment, our regimen can provide an alternative choice. Abstract Background: Biliary tract cancer (BTC) is a heterogenous collection of biliary tract cancer at different primary sites, and the prognosis of advanced BTC is dismal. Systemic chemotherapy with gemcitabine and cisplatin (GC) has been the reference regimen since 2010. How to improve therapeutic effects of GC regimen is an urgent mission at present. Methods: Bevacizumab with a reduced dosage and modified schedule (10 mg/Kg/triweekly, 1 day before GS at the first 2 cycles) was combined with standard GC for patients with advanced BTC. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 every 2 months. Kaplan–Meier curves were estimated for time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS). Result: A total of thirty cases of advanced BTC accepted this treatment, and the overall response rate (ORR) was 50.0%, and the disease control rate was 80.0% for all patients. The median TTF was 5.8 months, the median PFS was 8.4 months, and the median OS was 13.6 months. Most responses were noted at the first evaluation. Adverse effects (AEs) were mostly tolerable. Conclusions: After modifying the schedule, adding bevacizumab to a traditional GC regimen could increase the ORR with a shorter time-to-response, a better PFS and OS than GC alone but without the addition of AE. This regimen can be applied to patients with advanced BTC, especially those who are with a big tumor burden and who need a rapid response.

Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan. Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. The Brief Pain Inventory was used to assess pain intensity and QoL. Morisky’s four-item medication adherence scale was used to assess adherence to analgesic drugs. Clinical factors possibly associated with good adherence to analgesic drugs were analyzed using multivariate logistic regression analyses. Of the 897 patients, 26.9% met criteria for the good, 35.5% for the moderate, and 37.6% for the poor adherence groups. The good adherence group had significantly better QoL outcomes than the moderate and poor adherence groups (all p

Purpose Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. Methods 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1–14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1–14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. Results 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P Conclusion Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical trial registration NCT01808573

Our submission is the Correspondence to the text with the title of “Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis”. It was published in Br J Surg 2020; 107: 1811–1817.

Background: Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. Results: Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. Conclusions: Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

Background: Induction chemotherapy (IC) has a proven role in organ preservation and reducing distant failure. However, its ability to prolong survival remains controversy. Herein, we conducted a nationwide population‐based matched cohort study to investigate the association of primary tumor location with the role of IC in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) Methods: In this population based study, we retrospectively identified patients who aged 18 years and older with newly diagnosed LA-HNSCC between 2007 and 2016 from Taiwan National Health Insurance Research Database and Taiwan Cancer Registry. Patients were categorized into two group : IC group and definitive CCRT group. The primary tumor locations were classified into four part : oral cavity, oropharynx, hypopharynx and larynx. In order to reduce the selection bias, IC patients were individually matched at a ratio of 1 : 1 with the CCRT patients. The oncologic outcomes were presented with overall survival (OS). Findings: A total of 5547 patients were identified. After 1:1 matching, 1564 patients were analyzed for outcomes comparison, including 782 patients in each group. In general, median OS were 27.3 months versus 28.5 months in IC and CCRT group, respectively (p=0.6151). Patients were thereafter stratified by primary tumor location. For patients with oral cavity and laryngeal cancers, the median OS was significantly inferior in IC group than those in CCRT group, while for patients with oropharyngeal and hypopharyngeal cancer, the median OS was superior in IC group than those in CCRT group. Interpretation: IC has a divergent role in patients with different primary tumor location. Primary tumor location should be taken into consideration when facing the dilemma of IC followed by CCRT or definitive CCRT. Further prospective trials are warranted to confirm our results. Funding: This work was supported by the Room for Database Research of E-DA HEALTHCARE GROUP (grant no. EDCD2001) Declaration of Interest: The authors have nothing to declare Ethical Approval: This study was approved by the Institutional Review Board of the E-Da Cancer Hospital in Taiwan (EMRP-108-061), and the requirements for informed consent were waived.

Background PD-1/L1 inhibitors are treatment options for patients with HCC who have progressed after first-line sorafenib treatment. Tislelizumab, an anti-PD-1 monoclonal antibody, has demonstrated single-agent antitumor activity in patients with advanced, previously treated HCC in two early phase studies (NCT02407990, NCT04068519). Association of biomarkers, including PD-L1 expression and gene expression profiles (GEP), with response and resistance to tislelizumab were explored. Methods PD-L1 expression was evaluated on tumor cells (TC) using the VENTANA PD-L1 (SP263) assay in baseline tumor samples collected before or after sorafenib treatment. GEP were assessed using the 1392-gene HTG GEP EdgeSeq panel. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures (GS). Wilcoxon rank-sum test was used to analyze differential gene signatures (DEG); GS association with PFS and OS was evaluated using Cox proportional hazards models. Results Single-agent tislelizumab demonstrated antitumor activity in advanced, previously treated HCC (ORR=13%; CB [PR+SD >6 months]=31%, median PFS=3.3 months; median OS=13.3 months). PD-L1+ (TC≥1%) prevalence and GEP showed different patterns in samples collected before and after sorafenib exposure (figure 1). While non-exposed samples (n=16) were enriched for immune suppressive signatures, sorafenib-exposed samples (n=41) showed higher PD-L1+ prevalence (53.7% vs 25%; P=0.08) and immune-cell activation signatures along with co-inhibition molecules. In sorafenib-exposed samples, PD-L1 expression was positively correlated with CB (P=0.0027) and a trend of longer PFS (HR=0.56, 95% CI:0.28–1.13). ORR was higher in PD-L1+ than PD-L1− sorafenib-exposed samples (23.8% vs 0%; P=0.049). DEG analysis in sorafenib-exposed samples demonstrated that NK-mediated cytotoxicity GS was positively correlated with CB (P=0.03), as well as a trend of longer PFS (HR=0.43, 95% CI:0.17–1.06). Across the different analyses, no correlation with OS was observed. Patients considered non-responders (NRs) were found clustered into three distinct GEP subgroups (NR1, NR2, NR3). Compared with responders, NR1 had enhanced angiogenesis signatures (P=0.01), including TEK, KDR, HGF, and EGR1. Despite high inflamed tumor signatures, NR2 had increased expression of T-cell inhibition GS scores (P=0.01), including CD274, CTLA4, TIGIT, and CD96. The NR3 subgroup showed higher cell-cycle GS scores compared with responders (P=0.05), including E2F7, FOXA1, and FANCD2. Conclusions Prior sorafenib exposure appears to be associated with increased PD-L1 expression and tumor microenvironment-related GS, as well as response and PFS from tislelizumab in advanced HCC patients. Elevated angiogenesis, immune exhaustion, and cell-cycle GS levels may indicate resistance to single-agent PD-1 inhibitors and is suggestive of potential treatment strategies. Validation is warranted in future clinical trials (NCT03412773). Acknowledgements This study was sponsored by BeiGene, Ltd. Writing and editorial assistance was provided by Regina Switzer, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago. IL), and funded by the study sponsor. Trial Registration NCT02407990, NCT04068519

BackgroundThe programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.MethodsPatients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab’s safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.ResultsBetween May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1–2 severity; anemia (4.9%) was the most common grade 3–4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.ConclusionsTislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.Trial registration numberNCT02407990.

Aim To evaluate the prevalence of pain in cancer outpatients in Taiwan and to investigate the impact of pain on quality of life (QoL) and patient satisfaction. Results were compared to those of a similarly designed study conducted in 2008 to identify trends. Methods Adult patients with cancer treated as outpatients in hospitals throughout Taiwan were recruited. Pain intensity and the extent to which pain interfered with QoL were self-reported using a modified version of the Brief Pain Inventory. Patients also indicated their level of satisfaction with their physician, as well as with their pain control. Results A total of 2652 patients were enrolled from 16 sites. Of these, 1167 (44.0%) patients reported experiencing pain during the previous week. Prevalence and severity of pain were highest in patients with progressive disease. A higher pain severity score was significantly associated with greater interference in both physical and psychological functions. Overall, 86.0% of all participants expressed satisfaction with their physician and 84.8% were satisfied with their pain control; satisfaction rates were associated with pain severity. Compared with the findings from the 2008 study, pain prevalence was notably lower and patient satisfaction was significantly greater in the current study. Conclusions Prevalence and severity of pain were associated with disease stage. Pain interference on QoL correlated significantly with pain severity. Treatment of pain in cancer patients in Taiwan seems to have improved from 2008 to 2014, possibly attributable to new cancer pain treatment guidelines and the wider availability of novel analgesic therapies.

Background: Prognostic nutritional index (PNI) has been studied in various types of cancer which is significantly correlated with prognosis. The study aims to investigate the predictive role of PNI in patients with metastatic urothelial carcinoma (mUC) treated with systemic chemotherapy. Methods: We retrospectively reviewed 141 patients with mUC who received systemic chemotherapy. PNI was calculated as 10 × serum albumin concentration (g/dL) + 0.005 × lymphocyte count (number/mm2). The optimal cut-off value for PNI was estimated by using receiver operating curve analysis. Independent factors associated with progression-free survival (PFS) and overall survival (OS) were determined by Cox proportional regression models. Results: The recommended cut-off value for PNI was 40. Patients with a low PNI had more visceral metastases (p < 0.0001), leukocytosis (p = 0.006), and anemia (p < 0.0001). On univariate analysis, patients with a low PNI had poor OS than those with a high PNI (p < 0.0001). The multivariate analysis showed PNI was an independent factor to predict OS (p = 0.001). Conclusions: Our study showed PNI is an independent prognostic factor in patients with mUC. Our work is clinically useful for anticipation of outcomes, risks stratification in clinical studies as well as patients counseling.

Although cancer patients were satisfied with their physicians, treatment of cancer pain was still suboptimal. Guidelines should be revised to improve pain assessment and control in patients with cancer., Background We have limited knowledge about cancer patients’ pain control satisfaction in outpatient departments in Taiwan and doctors’ practice of adjusting analgesics according to their pain status. This survey examined pain management and satisfaction among cancer outpatients with pain and obtained information on their quality of life and treatment management for different pain intensities. Methods The Short version of the Brief Pain Inventory was used as the outcome questionnaire. Participants comprised 2075 patients with different cancers and disease statuses at 14 oncological outpatient departments, of which 1051 reported pain within the week prior to testing. The impact of pain management on physical and psychological functioning, and satisfaction with doctors were evaluated. Information about doctors’ prescriptions was collected. Logistic regression analyses were conducted to evaluate whether the interference scale performed identically in the different analgesic ladders. Results Pain was significantly linked to disease status and affected patients’ physical and psychiatric functioning. Almost 100% of patients were satisfied with their pain control, but more than 70% of doctors did not change analgesics based on patients’ current pain status. The results show that although patients were satisfied with their physicians, treatment of cancer pain was still suboptimal. Conclusion Pain assessment and treatment need to be more thorough and management guidelines should be revised to improve pain control in patients with cancer.

Neoadjuvant chemotherapy (NAC) is a widely‑used treatment for breast cancer, as it may render unresecta-ble breast tumors to become resectable. In addition, NAC provides the unique opportunity to assess response to treatments within months rather than years of follow‑up. However, predictive markers of tumor response to NAC are lacking. Therefore, the present study aimed to investigate the expression of endoglin, a marker of angiogenesis, and its association with pathologic responses to NAC. Samples from 34 breast cancer patients were obtained prior to and following NAC treatment. Immunohistochemical staining for endoglin and the mechanistic target of rapamycin (mTOR) was performed, and the correlation between the expression of these markers and pathologic response was examined. The overall response rate to NAC of these 34 patients was 67.6%. A mean microvascular density value of 14 served as a threshold score for the increased expression of endoglin. Increased expression of endoglin in primary tumors prior to NAC correlated with improved response in primary tumors (P=0.019) or in primary tumors and regional lymph nodes (P=0.014), when compared with reduced expression of endoglin. Increased expression of mTOR following NAC was additionally correlated with improved response to NAC. The results of the present study demonstrated that the expression of endoglin in breast tumor samples prior to NAC may be a predictor of treatment response. Long‑term follow‑up of clinical outcome is required to explain the elevation of mTOR expression levels following NAC treatment in responsive tumors.

Sorafenib is not recommended for advanced hepatocellular carcinoma (HCC) patients with Vp4 (portal invasion at the main trunk) by the Japan Society of Hepatology (JSH) due to a risk of hepatic failure. This study aimed to elucidate the safety and efficacy of sorafenib monotherapy on HCC with macro-vascular invasion (MVI). A total of 415 consecutive advanced HCC patients received sorafenib in our hospital. Patients with only MVI and sorafenib monotherapy were retrospectively enrolled. We enrolled 113 (27.2%) patients, including 56 (49.5%) Vp3 (portal invasion at the first branch) and 57 (50.5%) Vp4. Their median intervals of follow-up and sorafenib-use were 7.8 months and 2.7 months respectively. Using sorafenib, more Vp4 had hepatic decompensation (HD) (37% VS 18.2%, p = 0.028) than Vp3 patients. The multivariate analysis showed Vp4 (Odds ratio: 2.91; 95% CI: 1.02–8.3, p = 0.041) and baseline alpha-fetoprotein (AFP) ≥ 200 ng/ml were associated with HD. Dividing our patients into four subgroups as Vp3 + AFP < 200 ng/ml, Vp3 + AFP ≥ 200 ng/ml, Vp4 + AFP < 200 ng/ml and Vp4 + AFP ≥ 200 ng/ml, the proportions of HD were 16.7%, 19.4%, 16.7% and 55.2% respectively (p = 0.002). The overall survival rates were distributed with a significant decreasing trend as 10.2 ± 4.4 months, 6.5 ± 1.0 months, 6.0 ± 1.3 months and 2.5 ± 0.5 months (p = 0.001). We found only Vp4 plus AFP ≥ 200 ng/ml could induce more HD and a poorer prognosis than Vp3 patients. Hence, in Vp4 patients with higher AFP, sorafenib should not be the first-line treatment due to its limited survival benefit.

The emergence of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) caused a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). Although several clinicopathologic factors to predict the response to and survival on EGFR-TKI were recognized, its efficacy has not been confirmed for patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD). We conducted the study to evaluate the impact of COPD on survival for NSCLC patients that underwent EGFR-TKI treatment. The nationwide study obtained clinicopathologic data from the National Health Insurance Research Database in Taiwan between 1995 and 2013. Patients receiving EGRR-TKI were divided into COPD and non-COPD groups, and adjusted for age, sex, comorbidities, premium level and cancer treatments. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan&ndash, Meier analysis. In total, 21,026 NSCLC patients were enrolled, of which 47.6% had COPD. After propensity score (PS) matching, all covariates were adjusted and balanced except for age (p &lt, 0.001). In the survival analysis, the median OS (2.04 vs. 2.28 years, p &lt, 0.001) and PFS (0.62 vs. 0.69 years, p &lt, 0.001) of lung cancer with COPD were significantly worse than those without COPD. Lung cancer patients on EGFR-TKI treatment had a worse survival outcome if patients had pre-existing COPD.

Fatigue is a common and debilitating symptom in patients with advanced cancer, resulting in poor quality of life and reduced treatment efficacy. Phytotherapeutic agents have shown potential effects to relieve cancer-related fatigue in these patients. The aim of this study was to evaluate the efficacy and safety of Astragalus Polysaccharides injection and identify predictive factors associated with this treatment. Patients with advanced cancer receiving palliative care with moderate to severe cancer-related fatigue were enrolled in this study for two treatment cycles. Fatigue improvement response rates were analyzed as the primary endpoint at the end of the first cycle to determine treatment efficacy. The drug safety profile was evaluated by the reporting of adverse events. Three hundred and ten patients were enrolled in this study and 214 patients were included ITT population. Improvement in fatigue scores by at least 10% was observed in greater than 65% of subjects after one treatment cycle compared to scores at baseline. Patients with higher Karnofsky Performance Status (KPS) responded better to the Astragalus Polysaccharides injection. Drug-related adverse event rates were less than 9%. This study identified KPS as a promising predictive factor for the therapeutic efficacy of Astragalus Polysaccharides injection.

Background: Patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations have poor prognosis. We aimed to establish the efficacy of ramucirumab in patients with advanced hepatocellular carcinoma and α-fetoprotein concentrations of 400 ng/mL or higher. Methods: REACH-2 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 92 hospitals, clinics, and medical centres in 20 countries. Eligible patients were aged 18 years or older and had histologically or cytologically confirmed hepatocellular carcinoma, or diagnosed cirrhosis and hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage B or C disease, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group (ECOG) performance statuses of 0 or 1, α-fetoprotein concentrations of 400 ng/mL or greater, and had previously received first-line sorafenib. Participants were randomly assigned (2:1) via an interactive web response system with a computer-generated random sequence to 8 mg/kg intravenous ramucirumab every 2 weeks or placebo. All patients received best supportive care. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8), and time to deterioration in ECOG performance status. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with α-fetoprotein concentrations of 400 ng/mL or greater. Efficacy analyses were by intention to treat, whereas safety analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02435433. Findings: Between July 26, 2015, and Aug 30, 2017, 292 patients were randomly assigned, 197 to the ramucirumab group and 95 to the placebo group. At a median follow-up of 7·6 months (IQR 4·0–12·5), median overall survival (8·5 months [95% CI 7·0–10·6] vs 7·3 months [5·4–9·1]; hazard ratio [HR] 0·710 [95% CI 0·531–0·949]; p=0·0199) and progression-free survival (2·8 months [2·8–4·1] vs 1·6 months [1·5–2·7]; 0·452 [0·339–0·603]; p

Hung-Chih Hsu,1,2 Wen-Chi Chou,1,2 Feng-Che Kuan,2,3 Kuan-Der Lee,4 Kun-Ming Rau,2,5 Jen-Seng Huang,2,6 Tsai-Sheng Yang1,2 1Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Guishan, Taoyuan, Taiwan, Republic of China; 2College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, Republic of China; 3Division of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Puzi City, Taiwan, Republic of China; 4Division of Hematology and Oncology, Department of Medicine, Taipei Medical University Hospital and Taipei Medical University, Taipei, Taiwan, Republic of China; 5Division of Hematology and Oncology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; 6Division of Hematology and Oncology, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China Purpose: Fewer treatment options are available for refractory metastatic colorectal cancer (mCRC). In early trials, S-1 monotherapy was effective for mCRC patients after chemotherapy failure and its combination with oral leucovorin therapy offers promising results in untreated mCRC. Hence, we conduct a Phase II trial to assess the efficacy of S-1 plus oral leucovorin (SL) in refractory mCRC that progressed after multiple prior standard therapies.Methods: In this open-label, single-arm study, we enrolled the refractory mCRC patients who received fluoropyrimidine, oxaliplatin, and irinotecan treatment and at least one targeted therapy previously. The doses of SL were 40–60 and 30mg twice daily separately. They were administered for 7days in a 2-week cycle. Treatment was continued until disease progression.Results: Of the 41 enrolled patients, 36 patients were evaluable with 61.1% disease control rate. The median progression-free survival and overall survival were 2.55 and 7.63months, respectively. Regression change in tumor size stayed 10%–20% in five patients (13.9%) through 18weeks after treatment, and two patients continued free from tumor progression at 30 and 42weeks. Compared with moderate heavily pretreated mCRC patient subgroup (≤4 prior regimens), the severe heavily pretreated subgroup (≥5 prior regimens) showed similar disease control rate and survival benefit. Grade 3 or higher toxicities were documented only in 11 patients (26.8%).Conclusion: SL shows potential as a salvage regimen in refractory mCRC patients especially in the severe heavily pretreated setting and is well tolerated in these patients. Keywords: refractory metastatic colorectal cancer, S-1, oral leucovorin, Phase II, survival and safety

Objective Despite the significant role played by cancer patients' families in medical decision-making in Asian countries, inconsistencies have hitherto not been evaluated between patients' and families' preferences and doctors' actual practices with regard to cancer truth telling. Methods For this quantitative comparative study of cancer patients' and families' truth-telling preferences and their experiences of doctors' practices, 532 patients, 551 family members, and 127 doctors (N = 1 210) were enrolled from five hospitals across Taiwan over 2 years. Truth telling was assessed using the Taiwanese version of a modified Japanese truth-telling scale. Results Patients' truth-telling preferences and their experiences of doctors' truth-telling practices differed significantly in scores on the overall truth-telling scale and each subscale, including method of disclosure, emotional support, additional information, and setting (P

Objectives To create a novel prognostic model to predict survival in metastatic upper tract urothelial carcinoma patients treated with cisplatin-based chemotherapy. Methods After institutional review board approval, patients who had metastatic upper tract urothelial carcinoma and were treated with cisplatin based chemotherapy from 2000 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regress analyses. Kaplan–Meier curves were plotted to estimate overall survival. Several prognostic models were validated by using our cohort, and Harrell's c-index was calculated to evaluate their predicting performances. Results The present study consisted of 136 patients with a median age of 62 years and a median follow-up visit of 13.6 months. Multivariate analyses showed that renal function, performance status, liver metastasis and number of metastatic sites was independently related to survival. Based on these four variables, we constructed a prognostic model “renal function, performance status, liver metastasis, number of metastatic sites” with significantly different survival (P < 0.001). C-index results were renal function, performance status, liver metastasis, number of metastatic sites model 0.80 (0.69–0.90), Bajorin model 0.72 (0.61–0.83), Taguchi model 0.77 (0.67–0.87) and Tanaka model 0.78 (0.69–0.88). Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model achieved the highest c-index in this study. Conclusions Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model could be useful for providing prognostic information on survival in patients with metastatic upper tract urothelial carcinoma.

Background: Fluoropyrimidine- and platinum-based doublet regimen is the standard treatment of adjuvant chemotherapy (AC) for gastric cancer (GC). Our study aims to compare S1 with doublet regimens as AC in patients with advanced GC after radical surgery with D2 dissection. Methods: Patients who were diagnosed with GC and underwent a curative surgery with D2 dissection followed by AC were enrolled into our study. A propensity score matching analysis was performed to reduce the selection bias. Kaplan&ndash, Meier curves were estimated for recurrence-free survival (RFS) and overall survival (OS). Cox regression models were conducted for survival. Results: After propensity sore matching, 64 patients with S1 and 64 patients with doublet regimens were identified. The median RFS (p = 0.355) and OS (p = 0.309) were both insignificant between S1 and ST. Cox regression analysis demonstrated that pathologic stage and lymph node ratio (LNR) were independently correlated with survival. Patients were then stratified into low risk and high risk groups. The median RFS (p &lt, 0.001) and OS (p &lt, 0.001) had significant differences between low risk and high risk. In the high-risk group, doublet regimens were strongly associated with survival (p = 0.020) as compared with S1. While in the low-risk group, doublet regimen and S1 did not have statistically different survival benefits. Conclusions: Our study demonstrated that doublet regimens are superior to S1 in high-risk groups, and that survival outcomes are similar between doublet regimens and S1 in low-risk groups. Our prognostic model might have clinical implications for AC.

1082 Background: Our previous study ( Clin Cancer Res. 2015;21(8):1851) demonstrated that bevacizumab preconditioning followed by etoposide and cisplatin (BEEP) is a highly effective treatment for breast cancer (BC) patients (pts) with brain metastases (BM) progressing from WBRT. We conducted a randomized phase II study A-PLUS (NCT02185352) to test whether using BEEP as an induction therapy could enhance the efficacy of WBRT and provide systemic control. Methods: BC pts with measurable BM not suitable for surgery/radiosurgery and had not received WBRT were randomized (2:1) to experimental arm: induction BEEP for 3 cycles (~2 months [ms]) followed by WBRT or control arm: upfront WBRT. The BEEP regimen consists of bevacizumab 15 mg/kg on day 1, and etoposide 70 mg/m2/day on days 2-4, cisplatin 70 mg/m2 on day 2, followed by prophylaxis GCSF, every 21 days. After WBRT in both arms, pts received treatment of physician’s choice except BEEP until BM progression. Stratification was based on the Graded Prognostic Assessment score. Primary endpoint was brain-specific progression free survival (BS-PFS) based on RECIST 1.1, with a total of 108 pts, power of 0.8 at the 2-sided α level of 0.2. Results: Of 112 enrolled pts, 74 were in experimental arm and 38 in control arm. Baseline patient characteristics were generally balanced between arms. With median follow up of 28.7 ms, median BS-PFS was 8.1 vs. 6.5 ms ( p= 0.146; HR 0.71 [95% CI 0.44-1.13]), which met the primary endpoint (pre-defined α level of 0.2). Results of preplanned analysis included: 2-month brain-specific objective response rate of BEEP alone vs. WBRT was 41.9% vs. 52.6% ( p= 0.613); 8-month BS-PFS rate was 48.7% vs. 26.3% ( p= 0.027); median PFS was 6.4 vs. 4.7 ms ( p= 0.071; HR 0.67 [95% CI 0.43-1.04]), and extra-BM PFS was 7.9 vs. 5.0 ms ( p= 0.141; HR 0.71 [95% CI 0.46-1.12]). Median overall survival was 15.6 vs. 13.6 ms ( p= 0.855; HR 0.96 [95% CI 0.59-1.55]), with 31.6% of pts in control arm received BEEP regimen treatment after BM progression. The most common all-grade adverse events (AEs) in experimental arm were neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%). Most AEs were mild to moderate in severity. Two pts discontinued BEEP treatment due to grade 4 nephrotoxicity and grade 3 infection, respectively. Conclusions: BEEP as induction treatment followed by WBRT for BC pts with BM may improve control of both BM and systemic disease. Further validation by a phase III study is necessary. Clinical trial information: NCT02185352 .

549 Background: Intermediate-stage HCC, as defined as Barcelona Clinic Liver Cancer (BCLC) Stage B, is a heterogeneous disease in terms of liver function and tumor load. REACH (NCT01140347) and REACH-2 (NCT02435433) investigated ramucirumab (RAM) in patients (pts) with HCC after prior sorafenib (SOR), with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: All pts had HCC (BCLC stage C or B disease refractory/not amenable to locoregional therapy), Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or Placebo (P) Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was performed. Prognosis of BCLC staging in overall survival (OS) was evaluated by multivariate Cox PH model (adjusted for baseline AFP and treatment (trt) arm); Trt effects in BCLC stage B and C by Cox PH model; median OS/PFS were estimated by Kaplan-Meier method. Objective response rate (ORR) per RECIST v1.1, disease control rate (DCR), and adverse events (AEs) were also reported by BCLC. Liver function was assessed at baseline and prior to each trt with the Albumin-Bilirubin (ALBI) linear predictor. Results: Baseline characteristics were generally balanced between trt arms in each BCLC stage. BCLC staging trended as an independent prognosis factor for OS [B v C; HR = 0.756 (0.546, 1.046)]. A consistent trt benefit for RAM v P was observed across staging (Table). Grade ≥3 AEs were consistent with observations from both individual studies; hypertension was the most frequent grade ≥3 AE. No difference in liver function, as measured by ALBI, was observed between trt arms in either BCLC stage. Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit irrespective of BCLC stage. RAM was well tolerated and did not alter liver function compared to P. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]

Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.

Purpose The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. Methods This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. Results The survival rate at 24 months was 57.2% (95% CI 51.0–62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45–3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients’ tumors with the luminal A subtype had a significantly better objective response rate. Kaplan–Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p

The purpose of this study is to investigate the prevalence of pain, pain management, and impact of recent pain on daily functioning in patients with head and neck cancer (HNC) and patients with other cancers. This multi-center survey was conducted by using Brief Pain Inventory questionnaire to evaluate pain status and its impact on daily functioning. A total of 3289 patients were analyzed including 708 HNC patients and 2581 patients with other cancers. The overall pain prevalence was 69.17%. A higher percentage of HNC patients had recent pain (60.59 vs. 44.01%, P

Objective To investigate the prevalence of pain in cancer patients at different disease statuses, the impact of pain on physical and psychiatric functions of patients and the satisfaction of pain control of patients at outpatient clinic department in Taiwan. Methods Short form of the Brief Pain Inventory was used as the outcome questionnaire. Unselected patients of different cancers and different disease statuses at outpatient clinic department were included. The impacts of their current pain control on physical function, psychiatric function and the satisfaction of doctors were evaluated. Logistic regression analyses were performed to evaluate whether the interference scale performed identically in the different analgesic ladders. The dependent variables were satisfaction toward physician and treatment. Results A total of 14 sites enrolled 2075 patients in the study. One thousand and fifty-one patients reported pain within the last 1 week. In patients whose diseases deteriorated, >60% of them need analgesics for pain control. Pain influenced physical and psychiatric functions of patients, especially in the deteriorated status. More than 80% of patients were satisfied about current pain control, satisfaction rate related to disease status, pain intensities and treatments for pain. Conclusion Our study found that different cancers at different statuses had pain at variable severity. Pain can influence physical and psychological functions significantly. More than 75% of subjects reported satisfaction over physician and pain management in outpatient clinic department patients with cancer pain in Taiwan.

Purpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC). Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m2/day; days 2–4) and cisplatin (70 mg/m2; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)–objective response rate according to volumetric response criteria. Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33–75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9–89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a ≥80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5–8.1) and 10.5 months (95% CI, 7.8–13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%). Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. Clin Cancer Res; 21(8); 1851–8. ©2015 AACR.

To examine the effect of physical activity on the physical and psychosocial symptoms of lung cancer survivors. A longitudinal design was used in this study. Participants were recruited from the chest and surgical departments of medical centers in Taiwan. The instruments used were the Godin Leisure-Time Exercise Questionnaire and the Taiwanese version of the M.D. Anderson Symptom Inventory. In total, 185 survivors were followed up for 6 months (response rate 66 %). Disturbed sleep was the most prevalent symptom in the participants. A generalized estimating equation (GEE) method was employed to analyze the relationships among intensity of physical activity, symptom severity, and symptom interference in the daily life of the participants. Regarding symptom severity, significant differences were observed in fatigue, drowsiness, and disturbed sleep between the participants who engaged in moderate physical activity and those who did not engage in any physical activity. Regarding symptom interference, the participants who engaged in light physical activity experienced a significantly lower level of symptom interference than did those with a sedentary lifestyle. This is the first study to explore the role of physical activity in alleviating symptoms in lung cancer survivors by using the GEE method. The results suggest that physical activity plays an essential role in alleviating the physical and psychological symptoms of lung cancer survivors.

Background Males and females have significant differences in certain medical outcomes. However, little research has explored the gender differences in cancer patient perceptions of analgesics, the relationship between gender and analgesic adherence, or the effectiveness of pain management. Objective The objectives of this study were to compare gender differences associated with hesitancy to use analgesics, analgesic adherence, or pain management effectiveness and to examine whether gender can precisely predict analgesic adherence. Methods The study was conducted in the outpatient oncology department of a medical center in Taiwan. A descriptive and cross-sectional design was used. The study samples were collected from 362 cancer patients. The participants completed the short version of the Barriers Questionnaire-Taiwan, the Morisky Analgesics Adherence Measure-Taiwan version, the Brief Pain Inventory-Chinese version, the Pain Management Index, and a demographic and disease questionnaire. Results The pain intensity and hesitancy to use analgesics scores were significantly higher among females than among males. The Pain Management Index results indicated that a larger percentage of males had adequate pain management. In addition, being male was a significant predictor of higher analgesic adherence (odds ratio, 1.93; P Conclusions Gender could precisely predict cancer patients' medication adherence. Women experienced significantly greater pain than did men but also had more hesitancy to use analgesics, lower adherence, and inadequate pain management. Implications for practice Healthcare professionals should consider women as a high-risk group for inadequate pain control. It is crucial for health providers to consider the gender discrepancy when attempting to improve cancer pain management.

Purpose We developed a novel inflammation-based model (NPS), which consisted of a neutrophil to lymphocyte ratio (NLR) and platelet count (PC), for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC). Materials and Methods We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS) by using Kaplan–Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS. Results In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001) or PC (P < .0001). The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001). Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20–2.24, P = .002). Conclusion The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

Background Hospice care has been proved to result in changes to the medical behaviors of terminally ill patients. The aim of this study was to evaluate the effects and medical behavior changes of hospice-shared care intervention among terminally ill gastric cancer patients. Methods A total of 174 patients who died of gastric cancer between 2012 and 2014 were identified. These patients were divided into two groups: a hospice-shared care group (n = 93) and a control group (n = 81). Results Among the 174 patients, 84% had advanced stage (stage III or stage IV) cancer. The females and the patients cared by medical oncologists had a higher percentage of hospice-shared care than the males (71% vs 44%, p = 0.001) and those cared by other physicians (63% vs 41%, p = 0.004). Compared to the control group, the hospice-shared care group underwent lower incidence of life sustaining or aggressive medical treatments, including intensive care unit admission (2% vs 26%, p

Background.The EACH study assessed the efficacy of oxaliplatin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) compared with doxorubicin alone in terms of overall survival (OS), progression-free survival (PFS), and safety in patients with advanced hepatocellular carcinoma (HCC). We present the results of this study in Chinese patients. Methods. In a multicenter, open-label, randomized, phase III study (NCT00471965), 371 patients (279 patients from the People’s Republic of China) were randomized 1:1 to receive either FOLFOX4 or doxorubicin until disease progression, intolerable toxicity, death, or surgical resection. Results. BaselinecharacteristicsoftheChinesepatientsenrolled in the study were similar for the 2 treatment groups and in comparison with the whole EACH cohort. Median OS at the prespecified time point of treatment was 5.7 months with FOLFOX4 and 4.3 months with doxorubicin (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.55–0.98; p 5 .03). At the end of the follow-up period, median OS was 5.9 months with FOLFOX4 and 4.3 months with doxorubicin (HR: 0.75; 95% CI: 0.58–0.98;p5.03).MedianPFSwas2.4 monthsand1.7 months in the FOLFOX4 and doxorubicin groups, respectively (HR: 0.55; 95%CI: 0.45–0.78;p5.0002).Theresponserate(RR)anddisease controlrate(DCR)weresignificantlyhigherintheFOLFOX4group thaninthedoxorubicingroup(RR:8.6%vs.1.4%,p5.006;DCR: 47.1% vs. 26.6%, p 5 .0004). Hematological toxicity was more frequently reported in the FOLFOX4 group. Conclusion. For Chinese HCC patients enrolled in the EACH study, FOLFOX4 significantly improved the RR and DCR and prolonged survival compared with doxorubicin. Systemic chemotherapy with oxaliplatin-based regimens may play an important role in the treatment of Chinese patients with advanced HCC.The Oncologist 2014;19:1169–1178 Implications for Practice: We report the results of the EACH study for the subgroup of Chinese patients with advanced hepatocellularcarcinoma(HCC)whoareineligibleforcurativeresectionorlocaltreatment.Weshowedthatanoxaliplatin-based chemotherapy regimen (FOLFOX4; oxaliplatin, 5-fluorouracil, and leucovorin) significantly improved the response rate and the disease controlrate and prolonged survival compared with doxorubicin in Chinese patients. Oxaliplatin was approved by the ChinaFoodandDrugAdministrationforsystemicchemotherapyofHCC.TheFOLFOX4regimenisanaffordabletreatmentoption for most advanced HCC patients in the People’s Republic of China, and it may play an important role in the treatment of these patients.

Background. To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-2 and N1 disease. Patients and methods. A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling. Results. With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI. Conclusions. For patients with T1-2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.

4073 Background: Oral multikinase inhibitors that have shown improvements in overall survival (OS) in HCC are associated with clinically important toxicities that commonly require dose adjustment or discontinuation (D/C) due to intolerance. REACH and REACH-2 studied RAM in patients (pts) with HCC who progressed on or were intolerant to sorafenib (SOR), and REACH-2 only enrolled pts with baseline AFP ≥400 ng/mL. In REACH-2 RAM treatment (trt) improved OS compared to placebo (P), supporting findings in REACH pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by reason for D/C of SOR was performed. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or P Q2W. A pooled independent pt data analysis (stratified by study) of REACH-2 and REACH pts (AFP ≥400 mg/mL) was performed. Results are reported by reason for SOR D/C (intolerance or disease progression). OS and PFS were evaluated using Kaplan-Meier method and Cox proportional hazard model. Objective response rate (ORR), disease control rate (DCR) and safety are reported. Results: Baseline characteristics in the pooled population were generally balanced between trt arms in each subgroup. Median durations of prior SOR were 2.5 mo for SOR intolerant (n = 70) and 4.0 mo for SOR progressors (n = 472). Median OS (RAM v P) was 10.2 v 6.7 mo for SOR intolerant and 8.0 v 4.7 mo for SOR progressors (Table). Rates of D/C due to trt-related adverse events (AEs) (Table) (7% in each subgroup), and Grade ≥3 AEs (most frequently hypertension) were consistent with those observed in each study. Conclusions: Acknowledging limitations of sample size, the RAM trt benefit in SOR intolerant pts was consistent with that in the ITT population. RAM was well tolerated in SOR intolerant pts with low rates of D/C due to related-AEs. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]

326 Background: REACH-2 (NCT02435433) demonstrated a significant survival benefit with RAM vs placebo in the second-line treatment of patients with advanced HCC and AFP ≥ 400 ng/mL. This analysis investigated changes in AFP during treatment, as well as potential relationships with survival or progression. Methods: Patients were randomized (2:1) to RAM 8 mg/kg IV or placebo Q2W plus best supportive care until disease progression or unacceptable toxicity. Serum AFP levels were measured at baseline and every 3 cycles. Percent change in AFP from baseline was analyzed at each time point up to Cycle 12 with descriptive statistics and Wilcoxon rank sum test between treatment arms. AFP response was defined as ≥ 20% decrease from baseline. The association between AFP progression and radiographic progression in each time interval was assessed by odds ratio [OR] and Fisher’s exact test. Time to AFP progression and time to radiographic progression (TTP) were evaluated by the Kaplan-Meier method and compared between treatment arms using a stratified log-rank test. AFP progression was defined as ≥ 20% increase from baseline. Hazard ratio (HR) was generated using a stratified Cox regression model. Results: AFP response was significantly higher with RAM compared with placebo (42.1% vs 10.5%, p < 0.0001). Overall survival (OS) was longer in patients with AFP response (13.5 months) than in patients without (6.7 months), irrespective of treatment (HR 0.470, p < 0.0001). The median percent increase in AFP level from baseline was smaller in the patient population treated with RAM (0.4%, 6.1%, 15.4%, 10.8%) than with placebo (45.7%, 98.5%, 122.2%, 91.3%) at Cycles 3, 6, 9 and 12, respectively. Time to AFP progression (HR 0.422, p < 0.0001) and TTP (HR 0.427, p < 0.0001) favored a RAM benefit; subsequent analyses demonstrated a strong association between AFP progression and radiographic progression at 6 weeks (OR 2.44, p < 0.0084) and at 12 weeks (OR 1.89, p = 0.0430). Conclusions: Changes in AFP levels were associated with TTP and OS. RAM prolonged time to AFP progression and radiographic TTP, and slowed the rate of AFP increase during treatment. Clinical trial information: NCT02435433.

317 Background: In the phase 3 REFLECT study, lenvatinib (LEN) demonstrated a treatment effect on overall survival (OS) by statistical confirmation of non-inferiority to sorafenib (SOR) in patients (pts) with unresectable hepatocellular carcinoma (uHCC), who had not received prior treatment for advanced disease (Kudo M et al, Lancet 2018). Lenvatinib is approved in several major markets for the first line systemic treatment of uHCC. The most common adverse events (AEs) in pts treated with LEN were hypertension and diarrhea. In addition, LEN showed a different AE profile from that of SOR. Pts who received LEN experienced more instances of hypertension, proteinuria, dysphonia, and hypothyroidism than patients who received SOR. Recently, hypertension in LEN-treated pts with differentiated thyroid cancer was shown to be correlated with improved efficacy. Here we report the post hoc analysis exploring whether AEs associated with LEN were correlated with longer OS in REFLECT. Methods: 478 Pts were randomized to receive LEN (12 mg/d for actual body weight ≥ 60 kg or 8 mg/d for actual body weight < 60 kg). Subgroup analyses were conducted based on whether pts treated with LEN experienced any-grade AEs of interest (AEIs). OS was estimated by the Kaplan-Meier method. Results: The AEIs in pts treated with LEN were hypertension (42%), diarrhea (38%), proteinuria (24%), dysphonia (24%), and hypothyroidism (16%). OS was longer in pts who had several AEs of interest than in those who did not (table). Conclusions: In pts treated with LEN, the occurrence of hypertension, diarrhea, proteinuria, or hypothyroidism was generally associated with longer OS in pts with uHCC in this post hoc exploratory analysis. The potential confounding factors at baseline should be further investigated. Clinical trial information: NCT01761266. [Table: see text]

OBJECTIVES: Metachronous oesophageal squamous cell carcinoma (OSCC) has been increasing in long-term survivors of upper aerodigestive tract (UADT) cancers in recent years, but the treatment of such cases is not well established. The aim of this study was to compare the prognosis between patients with metachronous OSCC who had antecedent UADT cancers and patients with isolated OSCC. METHODS: From January 1995 to December 2009, we retrospectively compared the data from 84 patients with metachronous OSCC who had antecedent UADT cancers (metachronous group) with the data from 527 patients with isolated OSCC (isolated group) according to their treatment modalities at Kaohsiung Chang Gung Memorial Hospital. RESULTS: Overall, the metachronous group had significantly (P= 0.03) worse overall survival than the isolated group. For patients receiving surgery or preoperative chemoradiotherapy followed by surgery, the overall survival rates and incidence of postoperative complications were not significantly different. For patients receiving definite chemoradiotherapy or radiotherapy alone, the metachronous group had significantly (P= 0.02) inferior overall survival compared with the isolated group. CONCLUSIONS: Offering a radical approach for the treatment of patients with metachronous OSCC who had antecedent UADT cancers is justifiable, with survival rates similar to those of patients with isolated OSCC.

The outcomes of patients with metastatic gastric cancer (mGC) are poor. Recent studies have identified the prognostic impact of inflammatory response and nutritional status on survival for patients with gastric cancer. This study aims to create a prognostic model using inflammatory- and nutrition-based scores to predict survival in patients with mGC treated with chemotherapy. After institutional review board approval, patients who had mGC and were treated with chemotherapy from 2007 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regression analyses. Based on these variables, a prognostic model using inflammatory- and nutrition-based scores was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The c-statistic values with 95% confidence interval (CI) were also calculated to access their predicting performances. Our study consisted of 256 patients with a median age of 60 years and a median follow-up visit of 18.5 months. Multivariate analyses showed that neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and Patient-Generated Subjective Global Assessment (PG-SGA) were independently related to survival. After computing these scores, patients were classified into favorable-, intermediate-, and poor-risk groups. The median overall survival were 27.6 versus 13.2 versus 8.2 months in favorable, intermediate, and poor-risk groups, respectively. The 2-year survival rate was 52% versus 16% versus 3% in favorable-, intermediate-, and poor-risk groups, respectively. (P

Objectives The clinical characteristics and survival of very young (≤40 years) and very old ( > 80 years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients’ clinical characteristics and prognosis. Materials and methods Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included. Patients were divided into the following groups according to age: young (≤40 years), lower medium (41–60 years), higher medium (61–80 years), and very old (>80 years). Results Of the 555 patients, 20 (3.6%) patients were aged ≤40 years and 60 (10.8%) patients were aged >80 years. Young NSCLC patients had a lower BMI (p = 0.003), more brain (p = 0.016) and bone metastases (p = 0.002) Very young lung cancer patients still have poor prognosis even they were EGFR mutant. (EGFR mutant vs. wild type patients, OS: 12 vs. 7.3 months, p = 0.215) Very old NSCLC patients had a lower BMI (p = 0.003) and poor ECOG PS (p = 0.028). Positive EGFR mutation test reverses poor prognosis of elderly NSCLC patients. (EGFR mutant vs. wild type patients, OS: 13.2 vs. 4.9 months, p = 0.003) Conclusion We observed EGFR mutations reverse the poor prognosis of old patients with NSCLC. However, young patients with lung cancer have a poor prognosis even if they harbor EGFR mutations.