Studies That May Shift Treatment Paradigms in Gastric Cancer: A Review of Recent Trials
In 2017, new treatment approaches for patients with esophagogastric cancer have been investigated, including novel neoadjuvant regimens and immunotherapies.
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In 2017, new treatment approaches for patients with esophagogastric cancer have been investigated, including novel neoadjuvant regimens and immunotherapies, according to an oral presentation given at the 35th Annual Chemotherapy Foundation Symposium in New York.1
In trial ST03, researchers discovered that pre- and postoperative epirubicin, cisplatin, and capecitabine (ECX), with or without bevacizumab failed to provide a survival benefit to 1000 enrolled patients with esophageal and gastric cancer. Furthermore, rates of R0 resection with chemotherapy were relatively poor in patients with esophageal and gastroesophageal junction cancers (GEJ; 67%), leaving the authors uncertain about the adequacy of chemotherapy without radiation as a preoperative strategy for this patient population.
For trial OEO5, investigators enrolled 900 patients with esophageal and GEJ cancer to receive 2 cycles of cisplatin and 5-FU (CF) or 4 cycles of ECX. Preoperative chemotherapy without concurrent radiation resulted in poor rates of R0 resection (59% - 67%) among patients in both study arms, supporting the findings of trial ST03. When comparing the CF and ECX treatment groups, no difference in overall survival was observed.
Findings from the FLOT4 trial, however, may be practice changing for patients with gastric or GEJ cancers. For this trial, researchers administered perioperative epirubicin, cisplatin, 5-FU (ECF) or ECX, or a 24-hour infusion of 5-FU with leucovorin, oxaliplatin, and docetaxel (FLOT) to 716 patients.
Patients treated with FLOT had superior R0 resection rates (84% vs. 77%; P = .011), progression-free survival (PFS; 30 months vs. 18 months; hazard ratio [HR], 0.75; P = .0036), and overall survival (OS; 50 months vs. 35 months; HR, 0.77; P = .012), compared with patients treated with ECF/ECX. Five-year survival also improved from 31% to 41% among patients in the FLOT arm. The presenter noted, “FLOT will likely be adopted as the new standard for perioperative chemotherapy in patients with GEJ and distal gastric cancers, in patients capable of tolerating 3-drug chemotherapy.”
The safety and efficacy of 2 immunotherapeutic agents, nivolumab and pembrolizumab, was also explored.
Nivolumab or placebo were administered to 493 chemotherapy-refractory patients with gastric cancer in this phase 2 study. Approximately 82% of study patients previously received 3 or more lines of chemotherapy, and nearly 65% had undergone gastrectomy.
The median OS was prolonged from 4.1 to 5.3 months (HR, 0.63; P < .0001), and 1-year survival was also improved from 11% to 27% for patients receiving nivolumab. Eleven percent of patients in the nivolumab arm achieved response compared with none in the placebo arm.
An expansion cohort of a phase 2 study evaluating pembrolizumab in chemotherapy-refractory patients with gastric or GEJ led to positive results. Fifty-seven percent of patients in the study were positive for PD-L1 expression, 25% of patients had undergone gastrectomy, and 48% had received at least 3 prior lines of chemotherapy.
Overall, responses were reported in 11.6% of all study patients. Patients who were PD-L1 positive had a response rate of 15.5% compared with 6.4% among patients who were PD-L1 negative. Patients with microsatellite instability-high gastric cancer had a response rate of 57%. The 1-year survival rate was 23.5%, and median OS was 5.56 months.
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- Ilson DH. What new approaches are we looking at for gastric cancer? Oral presentation at: 35th Annual Chemotherapy Foundation Symposium; New York; November 8-10, 2017.