Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100

Abstract

Purpose: The role of maintenance therapy for gastric (GC) or gastroesophageal junction cancer (GEJC) is unclear. We investigated avelumab (anti-programmed death ligand-1 [PD-L1]) maintenance after first-line induction chemotherapy for GC/GEJC.

Patients and methods: JAVELIN Gastric 100 was a global, open-label, phase III trial. Eligible patients had untreated, unresectable, human epidermal growth factor receptor 2-negative, locally advanced or metastatic GC or GEJC. Patients without progressive disease after 12 weeks of first-line chemotherapy with oxaliplatin plus a fluoropyrimidine were randomly assigned 1:1 to avelumab 10 mg/kg every 2 weeks or continued chemotherapy, stratified by region (Asia v non-Asia). The primary end point was overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1-positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay).

Results: A total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250). Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .1779). In the PD-L1-positive population (n = 54), the HR for OS was 1.13 (95% CI, 0.57 to 2.23; P = .6352). In an exploratory analysis of the PD-L1-positive population, defined as combined positive score ≥ 1 (22C3 assay; n = 137), median OS was 14.9 months (95% CI, 8.7 to 17.3 months) with avelumab versus 11.6 months (95% CI, 8.4 to 12.6 months) with chemotherapy (unstratified HR, 0.72; 95% CI, 0.49 to 1.05). With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively.

Conclusion: JAVELIN Gastric 100 did not demonstrate superior OS with avelumab maintenance versus continued chemotherapy in patients with advanced GC or GEJC overall or in a prespecified PD-L1-positive population.

Trial registration: ClinicalTrials.gov NCT02625610.

FIG 1.

CONSORT diagram. AE, adverse event; BSC, best supportive care; FU, fluorouracil; PD, progressive disease.

FIG 2.

Overall survival (OS; measured from random assignment after 12 weeks of induction chemotherapy) in (A) all randomly assigned patients, (B) prespecified programmed death ligand-1 (PD-L1)–positive population (tumor cell PD-L1 expression, ≥ 1% cutoff; 73-10 assay), and (C) exploratory subset of patients with PD-L1–positive tumors based on combined positive score (≥ 1 cutoff; 22C3 assay). HR, hazard ratio; NR, not reached.

FIG 3.

Overall survival (OS; measured from random assignment after 12 weeks of induction chemotherapy [ie, re-baseline]) in subgroups. Hazard ratios (HRs) were calculated for a univariable unstratified model. In the microsatellite instability (MSI)–high subgroup, 12-month OS rate was 75.0% (95% CI, 31.5 to 93.1) in the avelumab arm and 40.0% (95% CI, 5.2 to 75.3) in the chemotherapy arm. CR, complete response; FU, fluorouracil; GEJ, gastroesophageal junction; NR, not reached; PR, partial response; SD, stable disease.

FIG 4.

Time to and duration of response (investigator assessed per RECIST [version 1.1]) during the maintenance phase (after random assignment) in (A) avelumab and (B) chemotherapy arms. Responses were based on subsequent change after random assignment (during maintenance) in patients who had achieved partial response (PR) or stable disease (SD) after induction chemotherapy. Excludes 10 patients with complete response (CR) during induction chemotherapy. NR, not reached; PD, progressive disease.

FIG 5.

Treatment-related adverse events (TRAEs) that occurred at any grade in ≥ 10% or grade ≥ 3 in ≥ 1% of patients in either arm during the maintenance phase (after random assignment). GGT, γ-glutamyltransferase; PPE, palmar-plantar erythrodysesthesia syndrome.

FIG A1.

Overall survival (OS; measured from random assignment after 12 weeks of induction chemotherapy) in (A) Asian patients and (B) subset with programmed death ligand-1–high tumors based on the 22C3 assay (combined positive score ≥ 10; 22C3 assay). HR, hazard ratio; NR, not reached.

FIG A2.

Progression-free survival (PFS; measured from random assignment to first documentation of progressive disease per RECIST [version 1.1] according to investigator assessment or death resulting from any cause, whichever occurred first) in (A) all randomly assigned patients, (B) prespecified programmed death ligand-1 (PD-L1)–positive population (≥ 1% of tumor cells; 73-10 assay), and (C) exploratory subset with PD-L1–positive tumors (combined positive score ≥ 1; 22C3 assay). HR, hazard ratio.