Background
Phase III open-label RCT, N=499 randomized (from 805 who received induction), HER2-negative previously untreated locally advanced or metastatic gastric or GEJ cancer. Patients without progressive disease after 12 weeks of first-line CAPOX or FP induction were randomized 1:1 to switch maintenance avelumab vs continued chemotherapy. JAVELIN Gastric 100 tested a switch-maintenance IO strategy.
Interventions and follow up
Arm A: Avelumab (anti-PD-L1) 10 mg/kg IV q2wk until progression or unacceptable toxicity
Arm B: Continued chemotherapy (CAPOX or FP, same backbone as induction)
Primary endpoint: Overall survival (all randomized patients and PD-L1-positive population)
Follow-up: 21.4 mo
Arm B: Continued chemotherapy (CAPOX or FP, same backbone as induction)
Primary endpoint: Overall survival (all randomized patients and PD-L1-positive population)
Follow-up: 21.4 mo
Results
mOS (all randomized): 10.4 vs 10.9 mo, HR 0.91, 95% CI 0.74–1.11, P=.18 (NS)
mOS (PD-L1+, 73-10 assay): HR 1.13, P=.64 (NS)
mOS (CPS ≥1, 22C3, exploratory): 14.9 vs 11.6 mo, HR 0.72 (exploratory only)
24-mo OS rate: 22.1% vs 15.5% (numeric trend)
mOS (PD-L1+, 73-10 assay): HR 1.13, P=.64 (NS)
mOS (CPS ≥1, 22C3, exploratory): 14.9 vs 11.6 mo, HR 0.72 (exploratory only)
24-mo OS rate: 22.1% vs 15.5% (numeric trend)
Adverse events
Grade ≥3 treatment-related: 12.8% (avelumab) vs 32.8% (chemo).
Immune-related: 29.5% (avelumab) vs 6.7% (chemo); tolerability favored avelumab over continued chemotherapy despite lack of efficacy.
Immune-related: 29.5% (avelumab) vs 6.7% (chemo); tolerability favored avelumab over continued chemotherapy despite lack of efficacy.
Conclusions
Switch maintenance with avelumab did not improve OS vs continued chemotherapy in HER2-negative advanced gastric/GEJ cancer, in either the overall population or the prespecified PD-L1-positive population. JAVELIN Gastric 100 is a practice-negative trial.
Key Limitations
Switch-maintenance design means patients already derived benefit from induction; the population is selected for non-progression (better prognosis). The PD-L1 assay used (73-10) may not select the same population as CPS (22C3). Concurrent IO is now standard as first-line (CheckMate 649, KEYNOTE-859), making a switch-maintenance design obsolete. Exploratory CPS ≥1 subgroup analysis (HR 0.72) was underpowered and hypothesis-generating only.
Clinical Context
JAVELIN Gastric 100 shows that switch-maintenance avelumab does not benefit gastric cancer patients, contrasting with avelumab's success in urothelial carcinoma (JAVELIN Bladder 100). In the modern era, first-line IO (nivolumab or pembrolizumab) is added upfront with chemotherapy (CheckMate 649, KEYNOTE-859), making maintenance IO strategies a moot point. PD-L1 testing with CPS (22C3) is preferred over TC scoring (73-10) for patient selection in gastric cancer.
References