Third-line chemotherapy in advanced gastric cancer

Zheng, Yu; Zhu, Xuqing; Ren, Xiaogang

doi:10.1097/md.0000000000006884

Cited by 28 publications

(12 citation statements)

References 30 publications

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“…To our knowledge, JAVELIN Gastric 300 and KEYNOTE-061 are the only randomised trials comparing anti-PD-1/PD-L1 antibodies with chemotherapy in patients with previously treated GC/GEJC. Although not approved for use in the third-line setting, chemotherapy is frequently used on the basis of several studies that have suggested improved patient outcomes relative to BSC or placebo [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300

et al. 2018

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BackgroundThere currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.Patients and methodsPatients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician’s choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.ResultsA total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9–1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4–2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.ConclusionsTreatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.Trial registrationClinicalTrials.gov: NCT02625623.

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Section: Discussionmentioning

confidence: 99%

Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300

et al. 2018

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“…4,5 Chemotherapy is one of the main additional methods in treatment, but the rise of drug resistance restricts its effect and might lead to treatment failure. [6][7][8] In order to solve this problem, we need to study the mechanisms of the chemotherapy resistance and find solutions.…”

Section: Introductionmentioning

confidence: 99%

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

Ruan¹,

Liu²,

Tao³

et al. 2020

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Gastric cancer is one of the most common malignant tumors, and it is also one of the leading causes of cancer death worldwide. Because of its insidious symptoms and lack of early dictation screening, many cases of gastric cancer are at late stages which make it more complicated to cure. For these advanced-stage gastric cancers, combination therapy of surgery, chemotherapy, radiotherapy and target therapy would bring more benefit to the patients. However, the drug-resistance to the chemotherapy restricts its effect and might lead to treatment failure. In this review article, we discuss the mechanisms which have been found in recent years of drug resistance in gastric cancer. And we also want to find new approaches to counteract chemotherapy resistance and bring more benefits to the patients.

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“…advanced gastric cancer who underwent third line chemotherapy had superior results to those who received optimal supportive care (10), but there is no comparison among different third line treatment, such as apatinib, nivolumab, and trifluridine/tipiacil. Based on the present analysis, nivolumab appeared to be the best option for OS.…”

Section: Discussionmentioning

confidence: 99%

“…Both irinotecan and taxane have been accepted as second line therapy (5). Increasing evidence from phase II or III trials have proved that salvage systematic therapy, including chemotherapy, target therapy, or checkpoint inhibitor therapy can prolong survival in patients who do not succeed with second line therapy (6)(7)(8)(9)(10), when compared with a placebo. But it is hard for clinicians to determine the best therapy, because there are no head-tohead randomized clinical trials (RCTs) to evaluate the efficacy and safety among the available third line therapies.…”

Section: Introductionmentioning

confidence: 99%

Role of Systemic Treatment for Advanced/Metastatic Gastric Carcinoma in the Third-Line Setting: A Bayesian Network Analysis

et al. 2020

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Background: Increasing evidences from phase II or III trials have proved that salvage systematic therapy, including chemotherapy, target therapy, or checkpoint inhibitor therapy can prolong survival in patients who do not succeed with second line therapy, yet there are no guidelines for the optimum third-line treatments. To compare the effectiveness and safety of current third-line therapies for metastatic Gastric Cancer (mGC), we conducted this network analysis. Methods: Literature up to Sep 30, 2019 were systematically searched and analyzed by a Bayesian fixed-effect model. Results: This study included seven randomized clinical trails which involved 2,655 patients. It turns out that for overall survival, nivolumab has the highest probability to be the optimal choice for overall survival (OS). For patients with no peritoneal metastases, the network meta-analysis showed that Nivolumab (HR:0.64; 95% CI: 0.48-0.85) and Trifluridine/tipiacil (HR:0.66; 95% CI: 0.51-0.86) were associated with significantly higher improvement in OS than placebo. However, patients with peritoneal metastases could not benefit from nivolumab, ramucirumab, or Trifluridine/tipiacil, when compared with a placebo. For progression-free survival, apatinib (850 mg) was the most likely candidate, followed by ramucirumab. Statistically, Apatinib (850 mg), Trifluridine/tipiacil, and SLC had higher incidences of high-grade adverse events (AEs) than placebo. Conclusion: Our findings demonstrate that nivolumab has the best balance between acceptability and effectiveness in the third line therapy for mGC.

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Third-line chemotherapy in advanced gastric cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 28 publications

References 30 publications

Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300

Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

Role of Systemic Treatment for Advanced/Metastatic Gastric Carcinoma in the Third-Line Setting: A Bayesian Network Analysis

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