RT Journal Article
SR Electronic
T1 Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 30
DO 10.1186/s40425-019-0508-1
VO 7
IS 1
A1 Chung, Hyun Cheol
A1 Arkenau, Hendrik-Tobias
A1 Lee, Jeeyun
A1 Rha, Sun Young
A1 Oh, Do-Youn
A1 Wyrwicz, Lucjan
A1 Kang, Yoon-Koo
A1 Lee, Keun-Wook
A1 Infante, Jeffrey R.
A1 Lee, Sung Sook
A1 Kemeny, Margaret
A1 Keilholz, Ulrich
A1 Melichar, Bohuslav
A1 Mita, Alain
A1 Plummer, Ruth
A1 Smith, Denis
A1 Gelb, Arnold B.
A1 Xiong, Huiling
A1 Hong, Janet
A1 Chand, Vikram
A1 Safran, Howard
YR 2019
UL http://jitc.bmj.com/content/7/1/30.abstract
AB Background We evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy.Methods In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety.Results Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5–13.9% and 1.8–16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0–not estimable) and 3.5 months (95% CI, 2.8–8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3–4.1) and 1.4 months (95% CI, 1.3–1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7–32.4%) and 7.9% (95% CI, 2.6–17.2%), and median OS was 11.1 months (95% CI, 8.9–13.7) and 6.6 months (95% CI, 5.4–9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4–20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death.Conclusion Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC.Trial registration ClinicalTrials.gov NCT01772004; registered 21 January 2013. Prior presentation Interim analyses were presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, San Francisco, CA, 21-23 January 2016 (abstract 167) and the ASCO Annual Meeting, Chicago, IL, 3-7 June 2016 (abstract 4009). Analyses reported in the current manuscript were presented at the American Association for Cancer Research Annual Meeting, Chicago, IL, 14-18 April 2018.Abbreviations:1 L-mnFirst-line switch-maintenance2 LSecond-lineAEAdverse eventCRComplete responseECOG PSEastern Cooperative Oncology Group performance statusGCGastric cancerGEJCGastroesophageal junction cancerHRHazard ratioORRObjective response rateOSOverall survivalPFSProgression-free survivalPRPartial responseSAESerious adverse eventSDStable diseaseTRAETreatment-related adverse event