Avelumab maintenance therapy administered after 12 weeks of frontline induction chemotherapy did not lead to a statistically significant overall survival (OS) benefit for patients with treatment-naïve HER2-negative advanced gastric or gastroesophageal junction (GEJ) cancer, causing the phase-3 JAVELIN Gastric 100 trial to miss its primary end point. The JAVELIN Gastric 100 dataset was published in the Journal of Clinical Oncology on November 16, following topline results from the trial (ClinicalTrials.gov Identifier: NCT02625610), presented in 2019.
JAVELIN Gastric 100 enrolled 805 patients between December 31, 2015 and November 29, 2017. After the 12-week induction period, 499 patients who achieved disease control were randomly assigned to receive either avelumab maintenance therapy (n=249) or continued chemotherapy (n=250). The number of patients with PD-L1–positive tumors (≥1% of tumor cells) was comparable in the avelumab and chemotherapy arms (30 vs 24).
Median OS was assessed at follow-up of 24.1 months and 24.0 months in the avelumab and chemotherapy cohorts, respectively. The primary end point was OS in the general study population and in patients with PD-L1–positive tumors. In the overall population, the median OS was 10.4 months (95% CI, 9.1-12.0) with the PD-L1 inhibitor and 10.9 months (95% CI, 9.6-12.4) with chemotherapy, with a hazard ratio of 0.91 (95% CI, 0.74-1.11; 1-sided P =.1779). The 24-month OS rate was slightly higher in the avelumab arm (22.1% vs 15.5%).
In the 54 patients with PD-L1–positive tumors, the median OS was 16.2 months (95% CI, 8.2-not reached [NR]) with avelumab and 17.7 months (95% CI, 9.6-NR) with chemotherapy (HR, 1.13; 95% CI, 0.57-2.23; 1-sided P =.6352).
Progression-free survival (PFS), a secondary end point of the JAVELIN Gastric 100 trial, favored chemotherapy in both the general and PD-L1 pre-specified populations. Specifically, the median PFS in the overall study population was 3.2 months (95% CI, 2.8-4.1 months) and 4.4 months (95% CI, 4.0-5.5 months) with maintenance avelumab and chemotherapy, respectively. In the PD-L1–positive subgroup, the median PFS was 5.6 months longer with chemotherapy (4.1 months vs 9.7 months; HR, 1.04; 95% CI, 0.53-2.02).
The investigators also noted a nonsignificant trend toward longer durations of response with avelumab vs chemotherapy in the overall population (probability of ongoing response at 24 months, 51.0% vs 13.5%).
No new safety signals were identified with avelumab; the agent’s safety profile was consistent with what was seen in prior studies of the immune checkpoint inhibitor, the study authors said. Lower rates of grade 3 or higher treatment-related adverse events (TRAEs) were seen with avelumab compared with chemotherapy (12.8% vs 32.8%). Permanent treatment discontinuations due to TRAEs also occurred at a lower frequency in the avelumab arm (10.3% vs. 27.3%).
The investigators of the JAVELIN Gastric 100 trial identified the study’s modest number of patients with PD-L1–positive tumors as a limitation, stating, “The low proportion of evaluable patients with PD-L1 – positive tumors…meant that the analysis of OS in this population was underpowered.” Nevertheless, Javelin Gastric 100’s results “are informative for future trials,” they said, adding that assessment of PD-L1 expression in both tumor and immune cells via combined positive could be useful in future investigations in gastric and GEJ cancer.
Disclosure: This clinical trial was supported by Merck KGaA as part of an alliance between Merck KGaA and Pfizer. Please see the original reference for a full list of the authors’ disclosures.
Moehler M, Dvorkin M, Boku N, et al. 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. J Clin Oncol. Published online November 16, 2020. doi: 10.1200/JCO.20.00892