Avelumab did not improve overall survival as frontline maintenance following induction chemotherapy in patients with unresectable, locally advanced, or metastatic HER2-negative gastric or gastroesophageal junction cancer.
Markus Möhler, MD, PhD
Avelumab (Bavencio) did not improve overall survival (OS) as frontline maintenance following induction chemotherapy in patients with unresectable, locally advanced, or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) cancer, according to topline results from the phase III JAVELIN Gastric 100 study.1
The PD-L1 inhibitor missed both OS-based primary endpoints, EMD Serono (Merck KGaA) and Pfizer Inc., the developers of avelumab, reported in a press release. In the intent-to-treat population of 499 patients, the hazard ratio (HR) for OS was 0.91 (95% CI, 0.74-1.11). Among the 54 patients in the PD-L1—positive subgroup, the HR for OS was 1.13; 95% CI, 0.57-2.23).
There were no new safety signals with avelumab, with a similar adverse event (AE) profile as other studies in the JAVELIN clinical development program. The developers plan to share the data once they have fully reviewed all of the findings.
“Advanced gastric cancer is a hard-to-treat tumor, and there is a key unmet need for additional treatments. Additionally, it is rarely immunogenic, and to date no immune checkpoint inhibitor has demonstrated superiority to the current standard of care with chemotherapy,” coordinating investigator of the trial Markus Möhler, MD, PhD, head of GI Oncology, senior physician Gastroenterology & Endosonography, Johannes-Gutenberg University, Mainz, Germany, said in the press release.
“As we have yet to define the ideal strategy for incorporating immunotherapy in the continuum of care, the results of JAVELIN Gastric 100 will provide essential information in advancing our understanding and potential treatment options of this challenging disease,” added Möhler.
The multicenter, open-label phase III JAVELIN Gastric 100 trial enrolled 805 patients with unresectable, locally advanced, or metastatic adenocarcinoma of the stomach or GEJ. Patients were treated with induction chemotherapy consisting of oxaliplatin plus 5-FU or capecitabine for 12 weeks. After the induction regimen, the 499 patients who had not progressed at 12 weeks were randomized to maintenance avelumab or to continue on the same chemotherapy regimen. Patients were treated until disease progression. Those assigned to the chemotherapy arm who were unfit for additional chemotherapy received best supportive care.
EMD Serono and Pfizer previously reported results from the phase III JAVELIN Gastric 300 trial, in which avelumab did not improve OS compared with chemotherapy in previously treated patients with gastric or GEJ adenocarcinoma.
The multicenter, international, open-label JAVELIN Gastric 300 trial included 371 patients with unresectable, recurrent, or metastatic gastric or GEJ adenocarcinoma whose disease progressed following 2 prior therapeutic regimens.2 Patients were randomized to best supportive care plus either avelumab or physician's choice of paclitaxel or irinotecan monotherapy. The study was conducted at 147 sites in  Asia,  Australia,  Europe,  North America,  and  South America.
The median OS was 4.6 months with avelumab compared with 5.0 months with chemotherapy (HR, 1.1; 95% CI, 0.9-1.4; P = 0.81). The median progression-free survival was 1.4 versus 2.7 months, respectively (HR, 1.73; 95% CI, 1.4-2.2; P >.99), and the median overall response rate was 2.2% versus 4.3%, respectively.
Grade ≥3 treatment-related AEs occurred in 9.2% of the avelumab group compared with 31.6% of the chemotherapy group.