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JAVELIN Gastric 100 Clinical Trial Results Demonstrate No Advantage for Avelumab vs Continued Chemotherapy

2021 Year in Review - Gastrointestinal Cancer

Avelumab maintenance therapy conveys no overall survival difference over the use of continued chemotherapy in patients with advanced GEJC or gastric cancer.

Advanced gastric and esophageal cancer have a poor prognosis despite treatment. Current treatment guidelines recommend triplet or platinum plus a fluoropyrimidine chemotherapy as the first-line treatment for advanced gastroesophageal junction cancer (GEJC) or HER2-negative gastric cancer. Nivolumab and pembrolizumab gained recent approval for maintenance therapy in patients with previously treated advanced GEJC or gastric cancer. Avelumab, like nivolumab and pembrolizumab, is an anti–PD-L1 monoclonal antibody that has been used to treat other cancers with an acceptable safety profile. Phase 2b studies have demonstrated it has antitumor activity as therapy in patients with previously treated advanced GEJC or gastric cancer. Building upon these results, the global phase 3 JAVELIN Gastric 100 trial further studied the use of avelumab as a maintenance therapy after induction chemotherapy in patients with advanced HER2-negative GEJC or gastric cancer. The primary end point of the study was overall survival (OS) in all patients and in patients with a PD-L1–positive combined score ≥1 tumors.

There were 805 patients from 17 countries enrolled in this study with untreated, unresectable, HER2-negative locally advanced or metastatic GEJC or gastric cancer who received induction chemotherapy. First-line induction therapy was 1 of 3 chemotherapy regimens for up to 12 weeks. After 12 weeks, 499 patients were determined to have disease control and were randomly assigned to continued chemotherapy or to receive 10 mg/kg avelumab every 2 weeks. Antihistamine/acetaminophen was given to patients receiving avelumab before infusion. Patients were stratified into Asia or non-Asia regions. Patients who were ineligible for further treatment received supportive care. Radiological tumor assessment was performed at baseline every 6 weeks for 12 months, and then every 12 weeks.

The median treatment duration for patients receiving avelumab was 3.2 months. Chemotherapy median treatment duration was 2.8 months. The treatment group receiving avelumab had a median OS of 10.4 months and a 24-month OS rate of 22.1%. The continued chemotherapy group median OS was 10.9 months with a 24-month OS rate of 15.5%. Analysis of OS among the PD-L1–positive patients found a median OS of 14.9 months for patients treated with avelumab and 11.6 months for patients treated with chemotherapy. Progression-free survival (PFS) for patients receiving avelumab was 3.2 months; it was 4.4 months for patients receiving chemotherapy. For the PD-L1–positive patients, the PFS for avelumab patients was 4.1 months and 9.7 months for chemotherapy patients.

Treatment-related adverse events (TRAEs) occurred in 61.3% of patients receiving avelumab and 77.3% of patients receiving chemotherapy. Grade ≥3 TRAEs occurred in 12.8% of patients receiving avelumab and common grade ≥3 TRAEs in this group included asthenia, decreased appetite, colitis, hypertension, pneumonitis, increased amylase, and increased lipase. In the avelumab group, 13.2% of patients experienced immune-related adverse events, with hypothyroidism, pneumonitis, and rash being the most common. In the group receiving chemotherapy, 32.8% experienced grade ≥3 TRAEs, with the most common being neutropenia, decreased neutrophil count, and peripheral neuropathy. One person died as the result of a TRAE in the chemotherapy group.

There was no advantage for use of avelumab maintenance over chemotherapy for the patients in this study.

Source: Moehler M, Dvorkin M, Boku N, et al. Phase 3 trial of avelumab maintenance after first-line induction chemotherapy versus continuation of chemotherapy in patients with gastric cancers: results from JAVELIN gastric 100. J Clin Oncol. 2021;39:966-977.

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