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Aim: To describe real-world treatment sequences of ramucirumab relative to immune checkpoint inhibitors (ICIs) in patients with advanced gastroesophageal cancer. Methods: Retrospective, observational study including adult patients treated with ramucirumab (April 2014–June 2020) from a nationwide health-record database. Results: In 1117 eligible patients, ramucirumab + paclitaxel was the most common ramucirumab-containing regimen (72.0%). A total of 217 patients also received an ICI. For ramucirumab then ICI (n = 148) and ICI then ramucirumab (n = 50), ramucirumab + taxane and ICI monotherapy were the most frequent approaches, most commonly observed as second- and third-line (2L and 3L). Median time on ramucirumab in 2L and 3L was similar regardless of sequence with ICI. Conclusion: Most patients with advanced gastroesophageal cancer received ramucirumab before ICI, with ramucirumab + paclitaxel as the most common ramucirumab-based regimen.

BACKGROUND: Gastric or gastroesophageal junction (GEJ) adenocarcinoma is the most common form of gastric cancer diagnosed in the United States (US) each year. Diagnosis typically is in later stages of disease when it has advanced. Patients have been treated with a variety of regimens. METHODS: The goal of this retrospective study was to understand if treatment patterns were becoming more homogeneous or remaining heterogeneous using the Herfindahl-Hirschman index (HHI) and if treatments were becoming more concordant to treatment guidelines published by the National Comprehensive Cancer Network (NCCN). HHI scores were calculated for each site by 2-year increments. Trend analyses were conducted for HHI scores over time using a linear regression model. Concordance to Category 1 and any category NCCN guidelines was determined based on the date treatment was initiated with the version of the NCCN guidelines at that time. Time trend analyses were conducted using linear regression models. This study utilized data from the Flatiron Advanced Gastric/Esophageal cohort. This study also examined overall survival (OS) rates estimated by the Kaplan-Meier method by line of therapy. RESULTS: There were no statistically significant differences in HHI scores in the first-line setting over time, suggesting heterogeneity has not improved. Concordance to NCCN treatment guidelines for any category significantly increased over time, however Category 1 regimen concordance remained low in the first-line setting. Concordance over time improved in second-line treatment. Median OS from the start of first-line therapy was 13.57 months. There was no relationship between OS time from initiation of first-line therapy and HHI score, concordance with NCCN guidelines, or concordance with NCCN Category 1 guidelines in the first-line setting. CONCLUSIONS: Treatment heterogeneity persists in gastric cancer care, though there is a significant association between heterogeneity and concordance with both Category 1 and any category in the NCCN treatment guidelines, and that concordance has increased over time.

Background: Despite the good prognosis with treatment for most patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) early breast cancer (EBC), ~ 20–30% of patients experience locoregional or distant disease recurrence. To assist in value assessments of novel therapies in the adjuvant setting, this study aimed to determine the costs of treated breast cancer recurrence following treated EBC. Methods: This retrospective study analyzed linked patient data from the US Surveillance Epidemiology and End Results (SEER) registry (2010-2014) and Medicare claims (2009 to 2019, which included data from Part A, B, and Prescription Drug Events [Part D]). Data were analyzed for patients aged ≥65 years with HR+, HER2-, node-positive EBC at high risk of recurrence (consistent with monarchE trial high risk criteria). Treated recurrences were defined based on treatment events/procedure codes, including surgery, radiation and systemic therapy, after a 90-day gap following the last treatment for initial EBC. Recurrences were classified based on Medicare claim diagnosis codes or SEER registry data. Extra cost was defined as cost attributable to treated recurrence. Cumulative extra costs were estimated by calculating cost differences between patients with treated vs non/untreated recurrence. Cumulative extra costs were analyzed over the first 6 years following first treated recurrence, a duration which ensured adequate sample size. Costs were inflated to 2021-US$. Results: We identified 3081 eligible patients (mean age at diagnosis 74.5±7.1 years, 97.4% female, 87.8% White). We identified 964 patients with treated recurrence (distant=432, locoregional=128, contralateral=9, unclassified=347) and 2117 patients with non/untreated recurrence. Six-year cumulative extra costs were higher for patients with distant recurrences ($168,656) than for patients with locoregional recurrences ($96,465) (Table 1). Conclusions: Cost of recurrence in patients with high risk EBC is considerable, particularly in patients with distant recurrences. Most patients who recurred in this population experienced distant recurrence. Delaying or preventing recurrence may reduce long term costs in these high risk EBC patients. Table 1. Mean cumulative extra costs attributable to treated recurrence. Citation Format: Alexandra S. Vitko, Pamela A. Martin, Sheng Zhang, Adam F. Johnston, Robert L. Ohsfeldt, Shen Zheng, Astra M. Liepa. Costs of breast cancer recurrence after initial treatment for high risk early breast cancer using SEER-Medicare linked data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-07-01.

Background Weight loss is common in advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA); however, the prognostic implications of weight loss during the first cycle (C1) of chemotherapy remain poorly characterized. In this study, we investigated the impact of early weight loss during systemic treatment as a potential prognostic factor for overall survival (OS) in patients with advanced G/GEA. Materials and Methods We performed a post hoc analysis of three phase III studies of ramucirumab. Patients were categorized into two groups: weight loss of ≥3% and, This article analyzes the impact of early weight loss during systemic therapy as a potential prognostic factor for overall survival in patients with gastric and gastroesophageal junction adenocarcinoma.

341 Background: The objective was to describe the safety of ramucirumab (Ram) for previously treated advanced gastric cancer under real-world conditions in Europe and North America. Methods: This was a non-interventional, descriptive study of adult patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease had progressed after first-line chemotherapy (I4T-MC-JVDD). Data collection began in December 2015 and was completed in August 2021. Patients were followed up to 12 months after initiation of Ram. Safety outcomes included adverse events (AEs)/serious AEs (SAEs), and AEs leading to dose adjustment or death. Subgroups of interest were elderly, patients with cardiac comorbidities, hepatic, or renal impairment. Results: 606 patients were classified in 3 cohorts: Ram monotherapy (Ram Mono, N=51); Ram plus paclitaxel (Ram+PTX, N=547); or Ram plus other anti-cancer agents (N=8). Most patients were male (70%), white (97%) and aged ≥65 (55%); 22% of the population was ≥75 years old. Metastatic cancer was reported in 552 patients (96%); primary tumor location was gastric in 417 patients (69%) and in the gastroesophageal junction in 189 patients (31%). Patients were previously treated mainly with platinum (97%) and fluoropyrimidine (96%). Hypertension was the most frequently reported historical medical condition (25%). At baseline, 23% patients had documented cardiac comorbidities, 11% hepatic impairment and 6% renal impairment. The median duration of Ram was 8 weeks (IQR=4.0-10.6) in Ram Mono and 15 weeks (IQR=8.4-26.7) in Ram+PTX. Regardless of causality, 98% of patients experienced ≥1 AE; most commonly fatigue (31%) and abdominal pain (20%) in Ram Mono cohort; and fatigue (46%) and neuropathy (31%) in Ram+PTX cohort. In total, 40% experienced ≥1 AE of special interest; most commonly bleeding/hemorrhage (21% [mainly epistaxis]) and hypertension (11%). In total, 33 patients (5%) died due to AEs that occurred on, or within 90 days of last dose of Ram, 9 (2%) were related to Ram treatment as per physician’s assessment. Conclusions: The observed safety profile of Ram in the real-world setting was manageable and consistent with the established safety profile of Ram identified from clinical trials. No new safety concerns or notable findings were observed overall or in the subgroups of interest. Clinical trial information: ENCEPP/SDPP/9400 . [Table: see text]

Background As real-world data resources expand and improve, there will increasingly be opportunities to study the effectiveness of interventions. There is a need to ensure that study designs explore potential sources of bias and either acknowledge or mitigate them, in order to improve the accuracy of findings. The objective of this study was to understand newly approved drug utilization patterns in real-world clinical settings over time. Methods This retrospective study included three sources of real-world data (claims, electronic health records, and recoded data from a quality care program) collected from patients diagnosed with gastric cancer who initiated therapy with either trastuzumab or ramucirumab. Linear regression was used to investigate trends in the use of these drugs for the care of patients with gastric cancer over time from Food and Drug Administration (FDA) approval. Results Eligible patients (n=1700) had consistent demographic and clinical characteristics over time. After regulatory approval, trastuzumab was used in later lines of therapy and then shifted to earlier lines (p=0.002), while ramucirumab utilization remained consistent over time after FDA approval (p=0.49). Ramucirumab augmentation, defined as the addition of the drug after initiation of a line of therapy, decreased over time (p=0.03), and trastuzumab augmentation remained consistent over time (p=0.58). Conclusion Since treatment effectiveness may change across lines of treatment, bias may arise if there are changes in the use of the drug (such as line migration) during the time period of analysis using real-world data.

Background Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonistplus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial.Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m 2 (60 mg/m 2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues.Findings Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7.4 months (IQR 3.5-13.9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4.1 months [95% CI 3.3-4.8] vs 2.8 months [2.6-2.9]; HR 0.696 [95% CI 0.573-0.845]; p=0.0002). Median overall survival was 9.4 months (95% CI 7.9-11.4) in the ramucirumab group versus 7.9 months (7.0-9.3) in the placebo group (stratified HR 0.887 [95% CI 0.724-1.086]; p=0.25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group.Interpretation Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Background Platinum and fluoropyrimidine combinations typically comprise first‐line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), although controversy exists regarding the use of 5doublet versus triplet cytotoxic regimens. Historically, second‐line (2L) and third‐line or later (3L+) therapy has been fragmented. Recent trials have increased the need for optimal treatment sequencing in advanced G/GEA. Materials and Methods We conducted a systematic search of peer‐reviewed manuscripts of randomized clinical trials examining 1L, 2L, and 3L+ therapy for advanced G/GEA published from 2009 through November 19, 2019. When available, overall survival, progression‐free survival, time to progression, overall response rate, and toxicity were extracted from each and compared descriptively. Results In 1L therapy, chemotherapy triplets demonstrated variable efficacy improvements with invariable increased toxicity compared with platinum/fluoropyrimidine doublets. Currently, the only published report of positive outcomes using biologics in 1L describes adding trastuzumab in HER2‐overexpressing advanced G/GEA. In 2L, doublet chemotherapy regimens are not uniformly more efficacious than single‐agent taxanes or irinotecan, and ramucirumab has demonstrated improved outcomes both as monotherapy and in combination. Conclusion For advanced G/GEA, review of trial results from 2009–2019 support 1L therapy with platinum and fluoropyrimidine and sequencing with taxanes or irinotecan in combination with biologics as effective 2L options. Escalating to a triplet may add some efficacy at the expense of added toxicity. Implications for Practice The rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first‐line platinum‐based regimens, identification of those with the best benefit‐to‐risk ratio may provide guidance on treatment sequencing strategies. This article presents findings from the published literature of randomized controlled trials that included a first‐line platinum/fluoropyrimidine combination and, for second‐line trials, patients with platinum/fluoropyrimidine‐refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first‐line regimen(s) followed by a strategy for subsequent regimens., This review evaluates evidence‐based treatment sequencing strategies for advanced gastric cancer and gastroesophageal junction adenocarcinoma, focusing on randomized controlled trials in which the commonly recommended platinum/fluoropyrimidine‐backbone was used in first‐line treatment and, for second‐line treatment, included a prior platinum and/or fluoropyrimidine.

This study was designed to describe health care resource utilization (HCRU) of patients with metastatic colorectal cancer (CRC) or gastric cancer to test the hypothesis that greater treatment variability would be associated with increased HCRU.A retrospective observational study using Marketscan claims data was conducted. Eligible patients had a first diagnosis of metastatic CRC or gastric cancer between 2004 and 2015 and must have received systemic anti-cancer therapy after diagnosis. Treatment variability was measured using the Herfindahl-Hirschman Index (HHI). HHI scores were stratified by quartile. HCRU variables were evaluated throughout the follow-up period and described by 6-month periods. Chi-square test was used for categorical variables and ANOVA for continuous variables.A total of 55,403 CRC and 9,073 gastric cancer patients were eligible. First-line HHI scores ranged from 0.1304-0.2778 for CRC and 0.0383-0.1778 for gastric cancer by state of residence. Statistically significant differences by HHI quartiles for HCRU in CRC included hospitalizations (Large sample sizes could lead to statistical significance without being clinically meaningful. High treatment heterogeneity in the gastric cancer cohort and lack of a homogeneous quartile for comparisons limited the ability to evaluate HCRU by different levels of treatment variability.Statistically significant relationships were observed between treatment variability as measured by HHI and increased HCRU, but no consistent directional trends in HCRU variables were observed. Therefore, this study failed to reject the null hypothesis of equivalent HCRU by level of treatment variability.

Background: Previous work has demonstrated treatment (tx) heterogeneity in the care of patients with aGC/GEJ. This study was designed to examine heterogeneity temporal trends and OS in patients with aGC/aGEJ in the United States from 2011 to 2018. Methods: The Flatiron Advanced/metastatic gastric/esophageal cohort electronic medical records (EMR) data were used for this study. Eligible patients were adults receiving anticancer therapy for aGC/GEJ during the study period. Tx patterns were summarized by line of therapy. Drugs were grouped by class. Heterogeneity was measured using the Herfindahl-Hirschman index (HHI); HHI scores range from 0.0000 (complete heterogeneity) to 1.0000 (complete homogeneity). A difference of 0.1000 in HHI scores is considered to be practically meaningful. HHI scores were calculated for each clinic with ≥10 patients. OS was estimated using Kaplan-Meier method. Trend analyses were conducted for HHI scores over time using a linear regression model. Results: There were 2,912 patients who met eligibility criteria. The median age of the study cohort was 67 years; majority were male (70.9%) and white (61.1%). aGC patients comprised the majority (n=1,630, 55.9%). Median OS from the start of first-line (1L) therapy was 12.7 months (95% CI: 12.07, 13.6). The most common 1L regimens were fluoropyrimidine + oxaliplatin (n=651, 22.4%), platinum (ie, cisplatin or carboplatin) + taxane (n=511, 17.5%), and single-agent fluoropyrimidine (n=280, 9.6%). 1,230 patients received second line (2L) and the most common regimens were ramucirumab + taxane (n=203, 16.5%), fluoropyrimidine + oxaliplatin (n=155, 12.6%), and platinum + taxane (n=101, 8.2%). Overall median HHI for 1L was 0.1728 (min/max: 0.0926–0.4380). Median 1L HHI for 2011–2012 was 0.21665 (min/max: 0.1626–0.3156) and was 0.2419 (min/max 0.1716–0.4583) for 2017–2018. There were no significant differences in HHI score over time (P=.078). Overall median HHI for 2L was 0.1309 (min/max: 0.0694–0.2400). Due to small number of sites with ≥10 patients, data in 2L were too limited to conduct time trend analyses. Conclusions: Heterogeneity in 1L treatment of gastric/GEJ cancer persists, despite the continued refinement of guidelines and approval of new drugs in subsequent lines of therapy. Further analyses are needed to examine the relationship between heterogeneity, guideline adherence, and patient outcomes. These future data will shed light on the persistence of heterogeneous treatment patterns observed in the United States.

Background In the intent-to-treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation. Materials and Methods Tumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR. Results In both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation. Conclusion Treatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. NCT01170663. Implications for Practice Ramucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first-line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.

Background and Objective Gastric cancer has been associated with notable geographic heterogeneity in previous multi-regional studies. In particular, patients from Japan have better outcomes compared with patients from other regions. Here, we assess patient-focused outcomes for the subgroup of Japanese patients in the global RAINBOW study. Methods Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) at baseline and 6-week intervals. Investigators assessed performance status before each 4-week cycle. Time-to-deterioration in each QLQ-C30 scale was defined as randomization to first worsening of ≥ 10 points (on a 100-point scale). Time-to-deterioration in performance status was defined as first worsening to ≥ 2. Hazard ratios were estimated using Cox proportional hazards models. Results The Japan subgroup contained 140 patients (ramucirumab plus paclitaxel, n = 68; placebo plus paclitaxel, n = 72); baseline QoL data were available for all patients. At baseline, QLQ-C30 scores were similar between study arms. Of the 15 QLQ-C30 scales, nine had a hazard ratio < 1, indicating similar or numerically longer time-to-deterioration in QoL for ramucirumab plus paclitaxel; all 95% confidence intervals included 1. Best mean change from baseline numerically favored ramucirumab plus paclitaxel in most QoL scales. The hazard ratios for time-to-deterioration of performance status to ≥ 2 were 0.64 in the Japan subgroup and 0.88 in the non-Asian subgroup. The Japan subgroup had better QoL at baseline compared with the non-Asian subgroup. Conclusions Treatment with ramucirumab plus paclitaxel maintained QoL and performance status over time compared with placebo plus paclitaxel in the Japan subgroup of the RAINBOW trial. These data suggest that the heterogeneity in gastric cancer between geographic regions includes multiple measures of QoL. Trial registration number NCT01170663 (first submitted 21 July, 2010). Electronic supplementary material The online version of this article (10.1007/s40261-020-00979-3) contains supplementary material, which is available to authorized users.

255 Background: With the advent of immunotherapy as an option for gastric, gastroesophageal junction (GEJ), or esophageal cancer, guidelines recommend testing for mismatch repair (MMR) or microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) at time of advanced cancer diagnosis. However, little real-world information is available on testing patterns and results for MMR/MSI and PD-L1. Methods: This study used the nationwide Flatiron Health electronic health record-derived de-identified database. Starting with a subset of 1594 patients (pts) from the Advanced Gastric/ Esophageal Cancer database who had initiated first-line (1L) treatment 01Jan2017-31Aug2020 and for whom additional abstraction for details on MMR/MSI and PD-L1 testing was conducted, adult pts with ≥3 months (mos) of follow-up were selected. 1L initiation was index date. For each biomarker, pts were classified as tested vs not. Pt and disease characteristics and test results were summarized. Testing relative to line of therapy and PD-1 inhibitor use were evaluated (data will be presented later). Results: Of 1142 eligible pts, 88% were initially diagnosed with advanced disease and 92% treated in community practice. 582 (51%) were tested for MMR/MSI and 571 (50%) for PD-L1; 451 pts were tested for both. MMR/MSI testing rates were 59% for gastric, 51% for GEJ, and 46% for esophageal. PD-L1 testing rates were similar across primary tumor sites (48-54%), but lower in those with squamous histology (38% for esophageal/GEJ). For both, testing increased over time with ̃40% in 2017 and 60% in 2020. For both, median number of tests per pt was 1 (range 1-6 for MMR/MSI, 1-4 for PD-L1). For both, mean time from initial diagnosis to first test was approximately 4 mos (> 5 mos in pts in 2017 and < 2 mos for those in 2020). Majority (> 68%) of all tests used tissue from primary tumor site. 46% of all MMR/MSI tests were performed with immunohistochemistry and 43% with next-generation sequencing; 5% were dMMR/MSI-H. 71% of all PD-L1 tests were performed using the commercial 22C3 assay. Reported composite positive score (CPS) results are summarized below. Conclusions: Rates of MMR/MSI and PD-L1 biomarker testing are increasing and time relative to initial diagnosis is shortening. A high proportion of pts tested positive for PD-L1 with CPS > 1. PD-L1 CPS varies by primary tumor site, histology, and tissue collection site. In the new era of 1L immunotherapy, increased rates of testing and reduced time to testing are likely to make more meaningful impact on treatment decisions.[Table: see text]

BackgroundTo evaluate patient-reported outcomes with ramucirumab plus docetaxel, a regimen which improved progression-free survival in platinum-refractory advanced urothelial carcinoma (aUC).MethodsRANGE—a randomized, double-blinded, phase 3 trial in patients with platinum-refractory aUC. Ramucirumab (10 mg/kg) plus docetaxel (75 mg/m2) or placebo plus docetaxel were administered every 21 days until disease progression or unacceptable toxicity. Patients received maximum 10 cycles of docetaxel. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EuroQoL five-dimensions (EQ-5D-5L) were administered at baseline, start of each cycle, and 30-day follow-up visit. A ≥ 10-point change in QLQ-C30 scores was considered meaningful. Rates of improved/stable scores were compared between treatment arms using Fisher’s exact test. Time to deterioration (TtD) was estimated and compared using Kaplan–Meier estimation and log-rank test.ResultsOf the 530 patients, ~ 97% patients in each arm provided baseline QLQ-C30 data. On-treatment compliance was ≥ 88% for first 8 cycles. Mean baseline QLQ-C30 scores were similar between arms, with global quality of life (QoL), fatigue, pain, and insomnia having greatest impairment. Postbaseline rates of improved/stable QLQ-C30 scores were similar between treatment arms except for greater improvement in pain score with ramucirumab. TtD of QLQ-C30 scales favored ramucirumab arm. Baseline EQ-5D-5L index and visual analogue scale scores were similar between arms, followed by relatively stable on-treatment scores. EQ-5D-5L scores worsened at post-discontinuation follow-up visit.ConclusionsRamucirumab plus docetaxel did not negatively impact QoL compared with docetaxel alone in platinum-refractory aUC. Improved TtD and tumor associated rates of pain favored ramucirumab treatment.Clinical trail registrationNCT02426125.https://clinicaltrials.gov/ct2/show/NCT02426125.Date of registration: April 24th 2015

Aims The ability of a patient to receive anti-cancer treatment depends on a variety of factors, including performance status (PS), which is typically measured using the Eastern Cooperative Oncology Group (ECOG) scale. This study hypothesized that there would be a strong and positive correlation between ECOG PS values and healthcare resource utilization (HCRU) and a strong and negative correlation with the use of anti-cancer therapy. Materials and methods Patients with colorectal, lung or gastric cancer were included in this retrospective analysis of administrative claims data linked to electronic medical records (EMR). All-cause HCRU (hospitalization/inpatient care, emergency room visits, systemic anti-cancer therapy, radiation therapy, outpatient physician visits, hospice, home health care and key supportive care treatments such as anti-emetics, hematopoietic treatments, transfusions, and durable medical equipment) was evaluated by baseline ECOG PS value and PS over time. Adjusted multivariable regression analysis was used to assess the relationship between baseline ECOG PS and HCRU. Regression analyses were conducted to explore the relationship between other baseline variables and HCRU. Results There were 1311 patients included in this study. There was low correlation between PS and any HCRU variable or receipt of anti-cancer therapy (correlation coefficients all

OBJECTIVE To describe treatment patterns and resource utilisation in France, Germany, Spain and the United Kingdom (UK) in patients with unresectable locally advanced and/or metastatic gastro-oesophageal adenocarcinoma (GEA), who failed first-line fluoropyrimidine/platinum treatment. METHODS Treating physicians completed a web-based chart review (2013-2015). Eligible patients were ≥ 18 years old; had unresectable locally advanced and/or metastatic gastric adenocarcinoma including the gastro-oesophageal junction; received first-line fluoropyrimidine/platinum-based therapy; and had ≥ 3 months of follow-up after first-line discontinuation. Data were summarised descriptively for each country. RESULTS There were n = 201 patients in France, n = 202 in Germany, n = 208 in Spain and n = 200 in the UK whose charts were reviewed. Percentages of patients receiving second-line therapy were 55% (France), 48% (Germany), 54% (Spain) and 29% (UK). At the start of second-line therapy, most patients had an ECOG performance status of 1 (range 0-3). Second-line therapy was primarily monotherapy, but agents used varied within and across countries. Supportive care use and resource utilisation were frequent whether receiving additional therapy or not; >60% patients had clinic visits unrelated to chemotherapy administration, and > 30% has ≥ 1 hospital admission. CONCLUSIONS For the time of study, established GEA treatment guidelines were generally followed. However, therapies varied widely in the second-line setting.

Limited real-world research has investigated ramucirumab for the treatment of patients with gastric or gastroesophageal junction (GEJ) cancer. This study was designed to describe ramucirumab monotherapy or combination therapy use in a community oncology practice setting. This was a retrospective observational cohort study to describe the treatment of adult patients with gastric or GEJ cancer who initiated ramucirumab treatment between 4/21/14 and 6/30/16 within the US Oncology Network. Kaplan–Meier method and Cox proportional hazards regression analyses were used to assess clinical outcomes. Multivariable logistic regression models were used to assess patient-level predictors of ramucirumab monotherapy or combination therapy. A total of 505 patients (mean age 64.4 years; 75.1% male) were included in the analysis; subgroups included: monotherapy (22.8%; n = 115), combination therapy (77.2%; n = 390). Monotherapy patients were significantly older (67.7 vs. 63.4 years; P = 0.0006), received ramucirumab approximately 3 months later after diagnosis (16.9 vs. 14.1 months; P = 0.0318) and more frequently initiated ramucirumab in the third or later lines of treatment (38.3 vs. 8.2%; P

152 Background: This study explored treatment patterns, and cancer-related resource use of patients with metastatic and unresectable gastric cancer (MGC) in South Korea. Methods: Charts of patients ≥ 18 years old were reviewed by 30 physicians to collect de-identified data on MGC or gastroesophageal junction adenocarcinoma [diagnosis on or after January 1, 2009]. Patients received platinum/fluoropyrimidine first-line therapy followed by second-line therapy or best supportive care, had no other primary cancer, and did not participate in a clinical trial following MGC diagnosis. Patient characteristics and treatment patterns were summarized using descriptive statistics. Results: Of 198 patients, 74% were male; 78% were diagnosed with MGC after age 55 (mean=61 yrs); 47% were current or former smokers and 48% reported light to moderate alcohol consumption. The majority of tumors were located in the antrum/pyloris (52%); metastatic sites most often occurred in the peritoneum (54%), lymph nodes (48%), and liver (39%). At diagnosis, the mean Charlson comorbidity index was 0.4 (std dev=0.6). The most common comorbidities were chronic gastritis (23%) and cardiovascular disease (19%). Most patients (80%) received second-line treatment (ECOG scores: 0 -10%, 1 -66%, 2 -22%); 20% received best supportive care only. Single-agent fluoropyrimidine was reported for 22% of patients receiving second-line treatment; 20% were treated with irinotecan with a fluoropyrimidine or platinum agent. Second-line treatment was chosen mainly according to national guidelines (81%) and physician experience (35%). The most common symptoms during second-line treatment were nausea/vomiting (45%) and pain (11%), with antiemetics (45%), analgesics (37%) and nutritional support (11%) most often used as supportive care. Two-thirds of inpatient hospitalizations (30% of second-line patients had ≥ one) were for chemotherapy infusion. Outpatient hospitalization (16%) and visits to the oncologist (38%) were common among second-line patients. Conclusions: Most patients received second-line treatment, though regimens varied. Understanding MGC patient characteristics and treatment patterns in Korea will help address unmet needs.

183 Background: For advanced upper gastrointestinal (GI) cancers, patient-reported symptoms are driven by both disease and treatment toxicities. This real-world longitudinal study was designed to evaluate patient-reported outcomes (PROs) of symptom burden and functioning among patients (pts) treated with anti-cancer therapy. Methods: Adult pts with advanced esophageal, gastroesophageal junction (GEJ), or gastric cancer were invited to participate in a prospective, longitudinal study. PRO assessment included pre-treatment and weekly completion of the M.D. Anderson Symptom Inventory GI module (MDASI-GI) as pts initiated a new line of therapy. Clinical and disease characteristics and treatment details were obtained from electronic health records. Up to 12 weeks longitudinal PRO data were analyzed using mixed-effect modeling with random intercept. Pts were classified into high or low symptom groups by group-based trajectory modeling. Time to deterioration in functioning (defined as a ≥2-point increase from baseline on 0-10 scale) was examined with Kaplan-Meier method. Results: At the interim analysis, 76 pts had enrolled: 33 (43%) were chemotherapy naïve for advanced disease, 18 (24%) had received 1 line of therapy, 14 (18%) had received > 1 line of therapy, and 11 (14%) were excluded from this analysis due to study discontinuation without follow-up assessment. Among the 65 eligible pts in this analysis, 46 (70.8%) were male, most were white (n = 56, 86.2%), and 44 (67.7%) had an ECOG performance status score of 0-1. Pain, fatigue, disturbed sleep, lack of appetite and inability to eat were the most common severe symptoms reported prior to and during therapy. Pts who had received one line of therapy reported worsening symptoms of pain, fatigue, lack of appetite, difficulty swallowing, and reduced general activity, work, and enjoyment of life over time (group and time interaction P 1 line of prior therapy had increased neuropathy symptoms (numbness/tingling) than those who were treatment-naïve ( P= 0.022). The median time to functioning deterioration of ≥2 points from baseline on the MDASI-“General activity” was 7 weeks. Up to 57% of pts were classified into high symptom trajectory group of pain, fatigue, disturbed sleep, and drowsiness with moderate to severe symptoms (≥4 points out of possible 10) over time; group membership was related to moderate to severe symptoms at baseline, after adjusting for age, sex, ECOG performance status, cancer site and prior therapies. Conclusions: This real-world observational study suggests that pts with advanced stage upper GI cancer undergoing standard therapy report high symptom burden. These preliminary findings support the use of a targeted symptom monitoring using well-defined PROs during active therapy, thereby adding the knowledge obtained from PROs to improve routine patient care.

Aim To describe treatment patterns, outcomes and healthcare resource use in patients with metastatic and/or locally recurrent, unresectable gastric cancer (MGC) in Taiwan. Methods Patients who had received first-line therapy (platinum and/or fluoropyrimidine) followed by second-line therapy or best supportive care (BSC) only were eligible. Participating physicians provided de-identified information from patient charts. Data were summarized descriptively and Kaplan–Meier analysis was used to describe time to events. Results Overall, 37 physicians contributed 122 patient charts. Of the 122 patients (median age, 61 years; 62% male), 43 (35%) received BSC only following first-line therapy, whereas 79 (65%) received second-line therapy. There was heterogeneity in second-line treatment, although fluoropyrimidine with or without a platinum agent was most frequently used. Median survival was 12.5 (interquartile range [IQR], 8.2–20.8) months from MGC diagnosis for patients receiving second-line therapy and 8.0 (IQR, 5.6–not reached) months for patients receiving BSC only. The most common treatment-related symptoms were nausea/vomiting (58%); the most common cancer-related symptoms were pain (61%), ascites (35%) and nausea/vomiting (33%). Inpatient and outpatient hospitalizations were numerically more common for patients receiving second-line therapy than for those receiving BSC only; the prevalence of hospice and skilled nursing facility stays were numerically more common for patients receiving BSC only. Conclusions In this Taiwanese MGC population, 65% received active second-line therapy with heterogeneity seen in the regimen used. Clinical outcomes suggest an unmet medical need in this population. This study may help inform clinical practice and future research to ultimately improve patient outcomes in Taiwan.

Purpose The purpose of this article was to describe the process and results of the preliminary qualitative development of a new symptoms-based patient-reported outcome (PRO) measure intended for assessing treatment benefit in clinical trials of advanced non–small cell lung cancer (NSCLC). Methods Individual qualitative interviews were conducted in adults with NSCLC (Stages I–IV) in the United States. Experienced interviewers conducted concept-elicitation (CE) and cognitive interviews using semistructured interview guides. The CE interview guide was used for eliciting spontaneous reports of symptom experiences along with probing to further explore and confirm concepts. Interview transcripts were coded and analyzed by professional qualitative coders, and were summarized by like content using an iterative coding framework. Data from the CE interviews were considered alongside existing literature and clinical expert opinion during an item-generation process, leading to the development of a preliminary version of the NSCLC Symptom Assessment Questionnaire (SAQ). Three waves of cognitive interviews were conducted to evaluate concept relevance, item interpretability, and structure of the draft items and to facilitate further instrument refinement. Findings Fifty-one subjects (mean [SD] age, 64.9 [11.2] years; 51.0% women) participated in the CE interviews. A total of 1897 expressions of NSCLC-related symptoms were identified and coded in interview transcripts, representing ~42 distinct symptom concepts. A 9-item initial-draft instrument was developed for testing in 3 waves of cognitive interviews with additional subjects with NSCLC (n = 20), during which both paper and electronic versions of the instrument were evaluated and refined. Participant responses and feedback during cognitive interviews led to the removal of 2 items and substantial modifications to others. Implications The NSCLC-SAQ is a 7-item PRO measure intended for use in advanced NSCLC clinical trials to support medical product labelling. The NSCLC-SAQ uses a 7-day recall period and verbal rating scales. It was developed in accordance with the US Food and Drug Administration’s PRO Guidance and scientific best practices, and the resulting qualitative interview data provide evidence of content validity. The NSCLC-SAQ has been prepared in both paper and electronic administration formats and a tablet computer–based version is currently undergoing quantitative testing to confirm its measurement properties and support US Food and Drug Administration qualification.

The phase III RAINBOW trial showed the addition of ramucirumab to paclitaxel yielded survival benefits for previously treated patients with advanced gastric or gastroesophageal junction adenocarcinoma. Now analyses reveal that ramucirumab also maintains patient-reported quality of life, lengthening the time to deterioration of patient symptoms and functions, and slowing performance status decline., Background The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine–platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. Patients and methods Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m2) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. Results Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. Conclusion In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. ClinicalTrials.gov NCT01170663.

We evaluated the safety and efficacy of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients previously treated for advanced gastric or gastroesophageal junction adenocarcinoma in Japanese and Western subgroups from the RAINBOW trial.Patients received ramucirumab at 8 mg/kg or placebo (days 1 and 15) plus paclitaxel at 80 mg/m(2) (days 1, 8, and 15 of a 28-day cycle). End points were compared between treatment arms within Japanese (N = 140) and Western (N = 398) populations.The incidence of adverse events of grade 3 or higher was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 83.8 % vs 52.1 %; Western population, 79.1 % vs 61.9 %). Neutropenia was the commonest adverse event of grade 3 or higher, with a higher incidence for ramucirumab plus paclitaxel (Japanese population, 66.2 % vs 25.4 %; Western population, 32.1 % vs 14.7 %). The incidence of febrile neutropenia was low and was similar between treatment arms in both populations. The overall survival hazard ratio was 0.88 (95 % confidence interval, 0.60-1.28) in the Japanese population and 0.73 (95 % confidence interval, 0.58-0.91) in the Western population. The progression-free survival hazard ratio was 0.50 (95 % confidence interval, 0.35-0.73) in the Japanese population and 0.63 (95 % confidence interval, 0.51-0.79) in the Western population. The objective response rate was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 41.2 % vs 19.4 %; Western population, 26.8 % vs 13.0 %), as was the 6-month survival rate (Japanese population, 94.1 % vs 71.4 %; Western population, 66.0 % vs 49.0 %).Safety profiles of the ramucirumab plus paclitaxel arm were similar between populations, though there was a higher incidence of neutropenia in Japanese patients. Progression-free survival and objective response rate improvements were observed for ramucirumab plus paclitaxel in both populations. CLINICALTRIALS.NCT01170663.

4543 Background: Treatment (tx) of advanced gastric cancer (GC/GEJ) is highly heterogeneous, with substantial variability in tx patterns. Frontline tx choice may affect outcomes of subsequent tx, thereby influencing choice/efficacy of second-line (2L) tx. In RAINBOW, 2L ramucirumab(R) plus paclitaxel(P) significantly improved overall survival (OS) of patients (pts) with GC/GEJ. Here we explore efficacy, safety and quality of life (QoL) based on prior tx. Methods: Pts were grouped into doublet (DB) or triplet (TP) regimens based on prior cytotoxic tx received. OS and PFS were estimated using Kaplan-Meier method and tx effects on OS and PFS were evaluated by Cox PH model; safety and QoL were assessed descriptively for DB vs TP. Results: Use of DB and TP was similar between arms, with 23% in R+P and 26% in placebo (PB)+P arm receiving TP. Baseline characteristics were generally balanced between tx arms within DB and TP subgroups, with majority of TP administered in western regions (91%). Pts ≥65 years of age was 40% for DB and 28% for TP. DB pts (n = 498; 75%) received S1+cis (n = 97, 15%) and cape+ox (n = 71; 11%) as most common prior tx, while TP pts (n = 163; 25%) received epi+cape+ox (n = 74, 11%) and epi+cis+5FU (n = 53, 8%). Similar to ITT population, R+P improved OS and PFS in both DB and TP subgroups (Table). Patterns of overall and Grade ≥3 TEAEs between arms were similar regardless of prior tx. Higher rates of serious TEAEs were reported in TP pts (57%, 49%) than DB pts (44%, 40%) in R+P and PBO+P arms, respectively. Similar trend was observed for TEAEs leading to discontinuation for TP (40%, 30%) vs DB (29%, 22%) in respective tx arms. Baseline QoL scores were similar between tx arms within subgroups, but mean scores were > 5 points worse (range 0-100) for prior TP for role functioning, fatigue, pain, and appetite loss. Changes in mean scores were generally similar between arms and within subgroups. Conclusions: This exploratory analysis of RAINBOW suggests that although safety-related outcomes were less favorable in pts with prior TP, regardless of tx arm, similar improvements in efficacy were noted for R+P irrespective of prior DB or TP. Clinical trial information: NCT01170663 . [Table: see text]

299 Background: Gastric cancer (GC, including gastroesophageal junction adenocarcinoma) pathways have been implemented and refined since 2010 in the US Oncology Network (USON), a community-practice-based network. This study was designed to evaluate the impact of 4 pathway periods (PP): pre-pathway: pre-Aug ‘10; Level 1: Sept ‘10-Nov ‘14; Clear Value, Dec ‘14-Feb ‘17; Value: After Mar ‘17, on treatment heterogeneity, treatment duration, and overall survival (OS). Methods: Adult patients were eligible if they were treated at a participating USON site and were diagnosed with and treated for GC; follow up was through Mar 2019. Heterogeneity was measured by the Herfindahl-Hirschman Index (HHI), which is evaluated from 0.0 to 1.0 (complete to no heterogeneity). Time to treatment failure (TTF) was defined as initiation of the line of therapy until start of the subsequent line of therapy or death. OS was estimated from start of first-line (1L) therapy. Time-to-event outcomes were estimated using Kaplan-Meier. Results: Of 3191 eligible patients, 2297 received treatment for advanced/metastatic disease. Of these, patient median age was 65.3 years, 60% were male, 70% were initially diagnosed with stage IV disease. Pre-pathway, common 1L regimens were single-agent fluorouracil (15%) and docetaxel-cisplatin-fluorouracil (14%); FOLFOX (45%) was most frequent during the value PP, 941 (41%) received second-line (2L) therapy. During Level 1 PP, single-agent irinotecan (11%) was most common during 2L, whereas in Value PP, ramucirumab+paclitaxel (43%) was most common. HHI and TTF are presented in the table. Median OS was 12.6 months (95% confidence interval, CI: 11.9, 13.5), which did not change significantly over PPs. Conclusions: 1L and 2L heterogeneity was initially high, and was reduced over time; TTF showed modest increase. OS data are limited by high levels of censoring in the latter PPs, which reduces the ability to evaluate changes in more recent years. [Table: see text]

Objective To estimate both the number of patients with hepatocellular carcinoma (HCC) eligible annually for second-line therapy following sorafenib in Germany and the healthcare costs accrued by patients meeting eligibility criteria. Methods Patients with an HCC diagnosis and one or more sorafenib prescription were identified from samples of > 3 million insured persons in each of 2012, 2013 and 2014 using the anonymised Betriebskrankenkasse health insurance scheme database. Incidence rates from 2013 were extrapolated to the German population using data from the statutory health insurance system database and Robert Koch Institute. Resource use and cost data were collected for a subset of patients with follow-up data post-sorafenib. Results Between 1032 and 1484 patients with HCC in Germany (893–1390 publicly insured patients) were estimated as likely to be eligible for second-line therapy after sorafenib annually. For post-sorafenib analyses, 117 patients were identified with HCC, one or more sorafenib prescription and considered potentially eligible for second-line treatment, 15 of whom were alive after 12 months’ follow-up. Total mean costs per patient accrued in the 12 months after sorafenib treatment ended were €11,152 (hospital care, €6483 [58.1%]; outpatient prescriptions, €3137 [28.1%]). Conclusion The estimated number of publicly insured HCC patients annually eligible for second-line therapy in Germany was

Inadequate understanding of interpretation of quality of life (QoL) instruments leads to unsatisfactory data reporting and clinical decision-making, including in gastric cancer care.Pooled QoL data from two phase III studies of ramucirumab with or without paclitaxel in previously treated patients with gastric or gastroesophageal junction cancer were used to explore associations with clinical attributes, including tumour response, disease measurability and performance status (PS). The European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ)-C30 was used in both studies. Changes in QLQ-C30 scores from baseline to week 6 as a predictor of clinical outcomes and impacts of changes in clinical status on QoL were estimated by multivariate logistic regression and analyses of variance, respectively.Baseline QoL data were available for 989 patients. Fatigue, pain and appetite loss were prominent baseline symptoms. Disease progression resulted in worse QoL in all functional scales (p 0.0001 to p = 0.0306), global QoL (p = 0.0011) and symptom scales (fatigue, p 0.0001; nausea/vomiting, p = 0.0007; pain, p = 0.0052; appetite loss, p = 0.0061). Similar trends were seen with deterioration of PS on QoL. A 15- to 20-point change in global QoL and functional scale scores predicted change in tumour status as did change in fatigue, pain and appetite loss scores. Smaller QoL changes (5-15 points) predicted PS change. Results were similar in patients regardless of baseline disease measurability.Our study underscores the importance of disease control for maintaining or improving QoL. These data could improve future trial design and routine clinical care for patients receiving therapy for previously treated gastric cancer. NCT00917384, NCT01170663.

Patients with metastatic gastric cancer have a poor prognosis (5-year survival of less than 10%). This study was designed to describe the treatment patterns of patients with gastric cancer and to understand the factors associated with treatment choices to inform evidence-based care. A retrospective observational study was conducted using two real-world databases to describe treatment trends and to quantify variability in treatment patterns of patients diagnosed with advanced/metastatic gastric cancer between 1/1/2007 and 9/30/2014 in the U.S. Heterogeneity was measured by the Herfindahl–Hirschman Index (HHI). Predictors (baseline clinical, treatment, and demographic variables) of treatment regimen choice were evaluated using logistic regression. A total of 5772 patients with advanced/metastatic gastric cancer were included in this study [5044 from claims data and 728 from electronic medical records (EMR)]. Of the 5044 from claims data, 2457 had evidence of metastatic disease at diagnosis. Only the fluorouracil + oxaliplatin regimen exceeded 10% utilization in the first-line setting [claims metastatic (12.1%), claims advanced (8.2%), and EMR metastatic (16.6%) cohorts]. The HHI demonstrated extreme heterogeneity (0.14 for first-line therapy and 0.13 for second-line therapy). Patient age and geographic region of residence were significantly associated with treatment choice across all three cohorts in the first-line setting (p

Objective Clinical trials have demonstrated improved outcomes for patients with diffuse large B-cell lymphoma (DLBCL) treated with regimens containing rituximab, but variations in real-world treatment patterns and outcomes have not been studied. The objective of this study was to characterize real-world treatment patterns and outcomes in higher risk DLBCL patients. Methods Patients with an International Prognostic Index score (IPI) ≥3 who received initial rituximab-based therapy from 2005 to 2012 were identified via electronic medical record data from the International Oncology Network. Initial therapy, rates of complete response (CR), post-CR treatments, and outcomes were evaluated. Results Among 257 eligible patients, 75% achieved a CR: 77% (158/206) of patients receiving R-CHOP compared to 71% (36/51) of patients receiving initial therapies other than R-CHOP. Post-CR, 78% of the 158 patients receiving R-CHOP underwent active surveillance; 13% received maintenance rituximab-based treatment; and 6% received radiation therapy. Relapse rates among patients receiving maintenance rituximab, active surveillance, and radiation therapy were 28% (6/21), 19% (24/124), and 0%, (0/10), respectively (P = 0.08). Discussion This study found that active surveillance continues to be the most commonly utilized treatment regimen among DLBCL patients with an IPI score ≥3 achieving a CR on first-line R-CHOP. Other approaches aimed at increasing the time to relapse are being utilized as well, but the clinical benefit of these modalities is unclear. Conclusion Results of this study are consistent with the results from clinical trials and suggest the need for further evaluation of maintenance therapy options for patients at higher risk of relapse.

Summary Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m 2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96–4·47] vs 2·76 months [2·60–2·96]; hazard ratio [HR] 0·757, 95% CI 0·607–0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8–30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4–18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1–2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Funding Eli Lilly and Company.

Aim: This retrospective observational study aimed to evaluate the epidemiology of advanced gastric cancer (GC) in Germany. Methods: Data were extracted from the Betriebskrankenkassen (BKK) database, which consists of different company health insurance funds throughout Germany and contains anonymized records of medical services. Patient data were retrospectively reviewed from January 2008 and followed prospectively until 31st of December 2011. The identification of GC patients (ICD-10 C16) was based on data from 2011 (main cohort). Two alternative approaches were used to detect patients with advanced GC who were treated with any first-line chemotherapy. Results: The database included 2 890 285 persons. In total, 3184 patients with a GC diagnosis were identified across all areas of medical care (main cohort). Of these, an estimated 585 patients (or 342, depending on the estimation approach) had advanced GC and received first-line chemotherapy. Age- and gender-adjusted extrapolation resulted in approximately 15 200 (8800) advanced GC patients in the entire German statutory health insurance system in 2011, equating to 22 (13) per 100 000 insured. It was estimated that 4119 (2416) advanced GC patients treated with first-line chemotherapy were newly diagnosed in 2011; an incidence rate of 6 (3) per 100 000 insured. Conclusion: This is the first retrospective observational study that provides plausible epidemiologic data of advanced GC in Germany. It gives a representative estimation of incidence and prevalence of patients with advanced GC who were treated with first-line chemotherapy in 2011 and could be potentially eligible for second-line therapy.

Summary Background Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer. Methods We did an international, randomised, double-blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa. Patients aged 24–87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were randomly assigned (2:1), via a central interactive voice-response system, to receive best supportive care plus either ramucirumab 8 mg/kg or placebo, intravenously once every 2 weeks. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00917384. Findings 355 patients were assigned to receive ramucirumab (n=238) or placebo (n=117). Median overall survival was 5·2 months (IQR 2·3–9·9) in patients in the ramucirumab group and 3·8 months (1·7–7·1) in those in the placebo group (hazard ratio [HR] 0·776, 95% CI 0·603–0·998; p=0·047). The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors (multivariable HR 0·774, 0·605–0·991; p=0·042). Rates of hypertension were higher in the ramucirumab group than in the placebo group (38 [16%] vs nine [8%]), whereas rates of other adverse events were mostly similar between groups (223 [94%] vs 101 [88%]). Five (2%) deaths in the ramucirumab group and two (2%) in the placebo group were considered to be related to study drug. Interpretation Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy. Our findings validate VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer. Funding ImClone Systems.

This study investigated the patient perspective during cancer treatment and throughout the survivorship period and to understand how the patient experience may be related to choices for the treatment of gastric cancer. Eligible patients in the Vector Oncology electronic medical records database were ≥18 years of age, diagnosed with gastric cancer, and received active treatment. Quality of life (QOL) was collected using the Patient Care Monitor (PCM). Time to deterioration in QOL and overall survival were measured, adjusting for demographic and baseline clinical characteristics. Logistic regression model and classification and regression trees (CART) were used to identify factors associated with treatment choice. There were 776 patients in this study, of whom 301 (38.8%) reported QOL data. Most patients reported problems on all PCM subscales; problems were more common during the treatment period. Median time to deterioration of PCM subscales ranged from 42 days for treatment side effects to 331 days for impaired performance. Median survival was low: 6.9 and 5.5 months from the start of first- and second-line therapy, respectively. The choices made between therapeutic options were primarily associated with the site at which the oncologist practiced. Patients with gastric cancer report a considerable number of concerns on all subscales of the PCM, particularly during active treatment periods. The treatment heterogeneity and relative lack of clinical and symptom- or QOL-related factors associated with treatment choice suggest a gap in evidence that must be filled.

This retrospective observational study was designed to evaluate overall survival in a real-world patient population and to identify predictive factors associated with receipt of second-line therapy. A retrospective analysis of electronic medical records (Flatiron Health, New York) was conducted among patients initiating first-line therapy from January 1, 2013, through April 30, 2018. Eligible patients were diagnosed with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma and ≥18 years of age at the time of treatment initiation. Patients alive 45 days after discontinuation of first-line therapy were considered potentially eligible for continued therapy and were categorized into those who received and those who did not receive second-line therapy. Survival analyses were conducted using Kaplan-Meier method and log-rank test without adjusting for any baseline covariates. Factors associated with further treatment were evaluated using logistic regression. A total of 3850 patients met eligibility criteria. Among the 2516 patients available to receive second-line therapy, 1515 (60.2%) received second-line therapy and 1001 (39.8%) did not receive further therapy. Among those potentially eligible to receive second-line therapy, median survival was 15.4 months (95% confidence interval [CI]: 14.6-16.0) from initiation of first-line therapy for those who received second-line therapy and 10.0 months (95% CI: 9.3-10.7) for those who did not. Longer duration of first-line therapy (≥169 vs ≤84 days), HER2-positive tumors, initially diagnosed with stage IV disease, less weight loss during first-line therapy, and younger age were associated with receipt of second-line therapy (all P < .001). Longer survival was associated with multiple lines of therapy; however, these results should be interpreted with caution, and no causal relationship can be inferred.

To describe treatment patterns, outcomes and healthcare resource use in patients with metastatic and/or locally recurrent, unresectable gastric cancer (MGC) in Taiwan.Patients who had received first-line therapy (platinum and/or fluoropyrimidine) followed by second-line therapy or best supportive care (BSC) only were eligible. Participating physicians provided de-identified information from patient charts. Data were summarized descriptively and Kaplan-Meier analysis was used to describe time to events.Overall, 37 physicians contributed 122 patient charts. Of the 122 patients (median age, 61 years; 62% male), 43 (35%) received BSC only following first-line therapy, whereas 79 (65%) received second-line therapy. There was heterogeneity in second-line treatment, although fluoropyrimidine with or without a platinum agent was most frequently used. Median survival was 12.5 (interquartile range [IQR], 8.2-20.8) months from MGC diagnosis for patients receiving second-line therapy and 8.0 (IQR, 5.6-not reached) months for patients receiving BSC only. The most common treatment-related symptoms were nausea/vomiting (58%); the most common cancer-related symptoms were pain (61%), ascites (35%) and nausea/vomiting (33%). Inpatient and outpatient hospitalizations were numerically more common for patients receiving second-line therapy than for those receiving BSC only; the prevalence of hospice and skilled nursing facility stays were numerically more common for patients receiving BSC only.In this Taiwanese MGC population, 65% received active second-line therapy with heterogeneity seen in the regimen used. Clinical outcomes suggest an unmet medical need in this population. This study may help inform clinical practice and future research to ultimately improve patient outcomes in Taiwan.

Summary Background Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here. Methods After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m 2 every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov, number NCT00102804. Findings Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio [HR] 0·76, 95% CI 0·59–0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34–0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 [4%] vs none; p=0·001), transfusions (42 [10%] vs seven [3%]; p=0·003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0·017). Interpretation Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy. Funding Eli Lilly.

Small cell lung cancer (SCLC) is associated with poor prognosis due to its early metastatic potential and lack of improved outcomes with newer cytotoxic agents. Identifying factors associated with clinical outcomes can help clinicians determine which patients are more likely to benefit from therapy. Functional Assessment of Cancer Therapy (FACT) subscales and Eastern Cooperative Oncology Group performance status (ECOG PS) were retrospectively analyzed as prognostic factors for overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage disease (ED)-SCLC.Using data from a Phase III trial of pemetrexed-carboplatin vs. etoposide-carboplatin, the effect of the prognostic factors on OS and PFS was analyzed via Cox models. The Kaplan-Meier method was used to estimate OS and PFS parameters for the prognostic subgroups (defined by baseline FACT scores and ECOG PS).Patients with higher baseline FACT-General (FACT-G) score (≥ median) had significantly higher OS (hazard ratio [HR]=0.62, P.0001) and PFS (HR=0.83, P=.032) compared with patients with lower FACT-G score (median). Similar results were observed for higher baseline physical well-being (PWB) and functional well-being (FWB) scores. For OS, there was a significant interaction between PS and FACT-PWB score (P=.005). In patients with PS=2 and higher FACT-PWB scores at baseline, a 48% reduction in the risk of death (P=.025) and nearly 3-month longer median OS were estimated.Higher baseline FACT-G, FACT-PWB, and FACT-FWB scores were found to be favorable prognostic factors for survival in ED-SCLC. Higher FACT-PWB scores at baseline predicted better survival for patients with poorer PS.