Dataset Information

Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data.

ABSTRACT:

Background

Second-line chemotherapy treatment of patients with relapsed gastric and oesophageal cancers in comparison with supportive care (SC) alone has been supported by recent phase 3 clinical trials, but a meta-analysis of patient-level data is lacking.

Methods

We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science for phase 3 clinical trials that compared second-line chemotherapy with SC alone for gastric and oesophageal cancers. A meta-analysis of the comprehensive patient-level data from the three identified trials was performed.

Results

A total of 410 patients with gastric (n=301), gastroesophageal junction (n=76), or oesophageal (n=33) adenocarcinoma were identified. In all, 154 patients received single-agent docetaxel and 84 patients received single-agent irinotecan, each with SC. SC alone was given to 172 patients. Chemotherapy significantly reduced the risk of death (hazard ratio (HR)=0.63, 95% confidence interval (CI)=0.51-0.77, P<0.0001). This effect was observed for treatment with docetaxel (HR=0.71, 95% CI=0.56-0.89, P=0.003) and irinotecan (HR=0.49, 95% CI=0.36-0.67, P<0.001). Overall survival (OS) benefit was greatest for patients who progressed 3-6 months following first-line chemotherapy (HR=0.39, 95% CI=0.26-0.59, P<0.0001). Performance status (PS) 0-1 compared with PS 2 (HR=0.66, 95% CI=0.46-0.94, P=0.02), locally advanced disease compared with metastatic disease (HR=0.41, 95% CI=0.25-0.67, P=0.0004) and older age (HR=0.94 per 5 years, 95% CI=0.90-0.99, P=0.01) were significant predictors of improved OS. Progression of disease during first-line treatment (HR=1.24, 95% CI=0.96-1.59) or within the first 3 months of completion of first-line treatment (HR=1.42, 95% CI=1.09-1.83) were predictors of an increased risk of death compared with progression between 3 and 6 months (P=0.03). Health-related quality of life outcomes were reported in only one of the three trials, precluding meta-analysis of these parameters.

Conclusions

This meta-analysis of patient-level data confirms that second-line chemotherapy treatment results in significantly better OS compared with SC alone in patients with platinum and fluoropyrimidine refractory gastric and oesphageal adenocarcinoma. Health-related quality of life outcomes should be included in future trials in this setting.

SUBMITTER: Janowitz T

PROVIDER: S-EPMC4815769 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data.

Janowitz Tobias T Thuss-Patience Peter P Marshall Andrea A Kang Jung Hun JH Connell Claire C Cook Natalie N Dunn Janet J Park Se Hoon SH Ford Hugo H

British journal of cancer 20160201 4

<h4>Background</h4>Second-line chemotherapy treatment of patients with relapsed gastric and oesophageal cancers in comparison with supportive care (SC) alone has been supported by recent phase 3 clinical trials, but a meta-analysis of patient-level data is lacking.<h4>Methods</h4>We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science for phase 3 clinical trials that compared second-line chemotherapy with SC alone for gastric and oesophageal canc ...[more]

PMID: 26882063

Similar Datasets

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:This study compares neoadjuvant chemoradiotherapy (nCRT) with perioperative chemotherapy (pCT) for patients with resectable esophageal or gastroesophageal junction (GEJ) adenocarcinoma in terms of toxicity, postoperative complications, pathologic response, and survival.This study retrospectively analyzed and compared 313 patients with resectable esophageal or GEJ adenocarcinoma treated with either nCRT (carboplatin/paclitaxel 41.4 Gy, n = 176) or pCT (epirubicin, cisplatin and capecitabine, n = 137).The baseline and tumor characteristics were similar in both groups. The ability to deliver all planned preoperative cycles was greater in the nCRT group (92.0 vs. 76.6%). Whereas nCRT was associated with a higher rate of grades 3 and 4 esophagitis, pCT was associated with a higher rate of grades 3 and 4 thromboembolic events, febrile neutropenia, nausea, vomiting, diarrhea, hand-foot syndrome, mucositis, cardiac complications, and electrolyte imbalances. Two patients in the pCT group died during neoadjuvant treatment due to febrile neutropenia. More postoperative cardiac complications occurred in the nCRT group. All other postoperative complications and the in-hospital mortality rate (nCRT, 4.7%; pCT, 2.3%) were comparable. The pathologic complete response (pCR) rate was 15.1% after nCRT and 6.9% after pCT. Radicality of surgery was comparable (R0: 93.0 vs. 91.6%). The median overall survival was 35 months after nCRT versus 36 months after pCT.For patients with esophageal or GEJ adenocarcinoma, chemoradiotherapy with paclitaxel, carboplatin and concurrent radiotherapy, and perioperative chemotherapy with epirubicin, cisplatin, and capecitabin lead to equal oncologic outcomes in terms of radical resection rates, lymphadenectomy, patterns of recurrent disease, and (disease-free) survival. However, neoadjuvant chemoradiotherapy is associated with a considerably lower level of severe adverse events and should therefore be the preferred protocol until a well-powered randomized controlled trial provides different insights.

Dataset Information

Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data.

Background

Methods

Results

Conclusions

Publications

Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure