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Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China.

ABSTRACT: AIM:That clinical trial (RAINBOW) showed that a 7.4 months overall survival benefit with the combination therapy with ramucirumab (RAM) and paclitaxel (PAC) as second-line therapy for patients with recurrent or metastatic gastric or gastro-oesophageal junction adenocarcinoma, compared with placebo (PLA) plus paclitaxel. We performed an analysis to assess the cost-effectiveness of RAM from a Chinese perspective and recognized the range of drug costs. METHODS:By building a Markov model to estimate quality-adjusted life-years (QALYs), life-years (LYs) and lifetime costs. Transition probabilities, costs and utilities were estimated for the published literature, Chinese health care system and local price setting. We performed threshold analyses and probabilistic sensitivity analyses to evaluate the uncertainty of the model. RESULTS:Compared with PLA strategy, RAM strategy provided an incremental survival benefit of 1.22 LYs and 0.64 QALYs. The probabilistic sensitivity analysis showed that when RAM costs less than $151 or $753 per 4 weeks, the incremental cost-effectiveness ratio (ICER) approximated the willingness-to-pay threshold (WTP), suggesting that there was 50% likelihood that the ICER for RAM + PAC would be less than $44528.4 per QALY or $48121 per QALY, respectively. CONCLUSIONS:For patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who fail first-line chemotherapy, our results are conducive to the multilateral drug price guidance negotiations of RAM in China.

SUBMITTER: Li S

PROVIDER: S-EPMC7205241 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China.

Li Sini S Peng Liubao L Tan Chongqing C Zeng Xiaohui X Wan Xiaomin X Luo Xia X Yi Lidan L Li Jianhe J

PloS one 20200507 5

<h4>Aim</h4>That clinical trial (RAINBOW) showed that a 7.4 months overall survival benefit with the combination therapy with ramucirumab (RAM) and paclitaxel (PAC) as second-line therapy for patients with recurrent or metastatic gastric or gastro-oesophageal junction adenocarcinoma, compared with placebo (PLA) plus paclitaxel. We performed an analysis to assess the cost-effectiveness of RAM from a Chinese perspective and recognized the range of drug costs.<h4>Methods</h4>By building a Markov mo ...[more]

PMID: 32379763

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Project description:Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9?months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9?months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P?=?0.573). Median overall survival (OS) was 10.9?months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3?months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P?=?0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07614-6.

Project description:BackgroundGastric cancer (GC) is a heterogenous disease consisted of several subtypes with distinct molecular traits. The clinical implication of molecular classification has been limited especially in association with treatment efficacy of ramucirumab or various targeted agents.MethodsWe conducted a prospective non-randomized phase II single-arm trial of ramucirumab plus paclitaxel as second-line chemotherapy in 62 patients with metastatic GC who failed to respond to first-line fluoropyrimidine plus platinum treatment. For integrative molecular characterization, all patients underwent pre-ramucirumab treatment tissue biopsy for whole-exome/whole-transcriptome sequencing to categorize patients based on molecular subtypes. We also systematically performed integrative analysis, combining genomic, transcriptomic, and clinical features, to identify potential molecular predictors of sensitivity and resistance to ramucirumab treatment.ResultsSixty-two patients were enrolled in this study between May 2016 and October 2017. Survival follow-up in all patients was completed as of the date of cut-off on January 2, 2019. No patient attained complete response (CR), while 22 patients achieved confirmed partial response (PR), resulting in a response rate (RR) of 35.5% (95% CI, 23.6-47.4). According to TCGA molecular classification, there were 30 GS, 18 CIN, 3 EBV, and 0 MSI tumors. The RR was 33% in GS (10/30), 33% in CIN (6/18), and 100% in EBV-positive GC patients with significant statistical difference for EBV(+) against EBV(-) tumors (P?=?0.016; chi-squared test). Moreover, responsive patients were marked by activation of angiogenesis, VEGF, and TCR-associated pathways, while non-responder patients demonstrated enrichments of sonic hedgehog signaling pathway and metabolism activity. Integrative multi-layer data analysis further identified molecular determinants, including EBV status, and somatic mutation in GNAQ to ramucirumab activity.ConclusionsProspective molecular characterization identified a subset of GC patients with distinct clinical response to ramucirumab therapy, and our results demonstrate the feasibility of personalized therapeutic opportunities in gastric cancer.Trial registrationThe study was registered on ClinicalTrial.gov ( NCT02628951 ) on June 12, 2015.

Project description:BackgroundFirst-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.MethodsIn this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116.FindingsFrom March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified.InterpretationNivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients.FundingBristol Myers Squibb, in collaboration with Ono Pharmaceutical.

Project description:ImportanceRamucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting.ObjectiveTo compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer.Design, setting, and participantsThis phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapy-naive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018.InterventionsPatients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m2, on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m2, on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle).Main outcomes and measuresThe primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events.ResultsIn total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm compared with the placebo plus S-1 and oxaliplatin arm (6.34 [80% CI, 5.65-6.93] vs 6.74 [80% CI, 5.75-7.13] months; HR, 1.07; 80% CI, 0.86-1.33; P = .70). Median overall survival was 14.65 (80% CI, 12.39-15.67) months in the ramucirumab plus S-1 and oxaliplatin arm and 14.26 (80% CI, 13.83-17.31) months in the placebo plus S-1 and oxaliplatin arm (HR, 1.11; 80% CI, 0.89-1.40; P = .55). The most commonly reported grade 3 or higher treatment-emergent adverse events in the ramucirumab plus S-1 and oxaliplatin arm in part A were decreased neutrophil count (14 patients [14.6%]), hypertension (10 patients [10.4%]), and anemia (10 patients [10.4%]).Conclusions and relevanceIn this randomized clinical trial, the addition of ramucirumab to first-line S-1 and oxaliplatin treatment did not prolong progression-free survival or overall survival compared with S-1 and oxaliplatin alone among East Asian patients with advanced gastric cancer; no new safety signals for ramucirumab were identified.Trial registrationClinicalTrials.gov identifier: NCT02539225.

Project description:BackgroundRamucirumab (RAM) with weekly paclitaxel (wPTX) is a standard second-line therapy for advanced or recurrent gastric cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX), an albumin-bound form of PTX, was developed to improve the therapeutic index of taxane treatment. However, the ABSOLUTE trial showed the non-inferiority of weekly nab-PTX (w-nab-PTX) to wPTX with respect to overall survival (OS) as second-line therapy for advanced or recurrent gastric cancer, and subgroup analysis of patients with peritoneal dissemination showed favourable OS and progression-free survival (PFS) in the w-nab-PTX arm compared to those in the wPTX arm. This study evaluated whether w-nab-PTX plus RAM is more effective than wPTX plus RAM for patients with peritoneal dissemination.MethodsThe P-SELECT trial (WJOG10617G) is a prospective, open-label, multicentre, randomised phase II study evaluating wPTX plus RAM (arm A) versus w-nab-PTX plus RAM (arm B). Key eligibility criteria include the following: 1) histologically proven adenocarcinoma, 2) unresectable or recurrent gastric cancer, 3) peritoneal dissemination, 4) intolerance or refractory to first-line therapy including fluoropyrimidines, and 5) ECOG Performance Status (PS) 0-2. Patients are randomised to either arm at a 1:1 ratio stratified by institution, PS, and severity of ascites. PTX (80?mg/m2; days 1, 8, and 15) and RAM (8?mg/kg; days 1 and 15) are administered every 4?weeks in arm A, while nab-PTX (100?mg/m2; days 1, 8, and 15) instead of PTX is administered in arm B. The primary endpoint is OS, and the main secondary endpoints are PFS, objective response rate, safety, neuropathy-specific quality of life, and biomarkers. To maintain a probability of ?70% to ensure the hazard ratio for OS in arm B is lower than 0.90, 105 subjects are required. The study was initiated in October 2018 and is being conducted in 58 centres of the West Japan Oncology Group.DiscussionThe results of this study will determine whether w-nab-PTX plus RAM has the potential to be a preferred therapeutic option for advanced and recurrent gastric cancer with peritoneal dissemination, compared to wPTX plus RAM.Trial registrationThis study was prospectively registered in the Japan Registry of Clinical Trials (jRCTs031180022, October 1, 2018).

Project description:BackgroundIn 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 methodsTumor 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.ResultsIn 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.ConclusionTreatment 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 practiceRamucirumab 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.

Dataset Information

Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China.

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Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China.

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