SAN FRANCISCO — Mixed results emerged from studies evaluating the efficacy of two novel therapies for patients with metastatic gastric cancer, researchers reported.
In one study, trifluridine/tipiracil (FTD/TPI, Lonsurf) was shown to be an effective treatment option for patients with metastatic gastric cancer, regardless of prior gastrectomy.
In the other, the monoclonal antibody andecaliximab plus the chemotherapy regimen mFOLFOX6 (mFOLFOX + ADX) as a first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma failed to improve overall survival.
Both studies were presented here at the 2019 Gastrointestinal Cancers Symposium.
According to David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, who presented the study on FTD/TPI, the only potentially curative treatment for early stage gastric cancer is surgery, with 5-year survival rates after gastrectomy of 90% or more in Japan and Korea and 40% to 75% in non-Asian countries.
Furthermore, the disease recurs in up to half of patients, while 40% of patients with metastatic disease have had a previous gastrectomy.
The phase III TAGS study had demonstrated that FTD/TPI is effective and safe for patients with heavily pretreated metastatic gastric cancer. Here, Ilson and his colleagues evaluated the efficacy and safety of the FTD/TPI in patients with or without gastrectomy.
Patients were randomized two-to-one (337 in the FTD/TPI arm and 170 in the placebo arm) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo.
Of the 507 patients in the study, 147 in the FTD/TPI arm had a prior gastrectomy compared to 74 in the placebo arm.
In the total study population, median overall survival was 5.7 months in the FTD/TPI arm compared to 3.6 months in the placebo arm (HR 0.69). Progression-free survival was 2.0 vs 1.8 in the FTD/TPI and placebo arms, respectively (HR 0.57).
The overall and progression-free survival data of patients with prior gastrectomy “mirrored the data seen in the overall treatment population,” Ilson reported, with overall survival improving by 2.6 months in the FTD/TPI arm (HR 0.57).
As for safety, hematologic adverse events such as neutropenia/leukopenia were more frequent among those patients treated with FTD/TPI, but these did not lead to more frequent treatment discontinuation.
“I think the data from this study reinforce the benefit of TPI as prolonging survival versus placebo, regardless of gastrectomy,” Ilson concluded.
In a prior phase I/IB study, the combination of mFOLFOX6 and ADX “revealed encouraging anti-tumor activity in patients with gastric or gastroesophageal junction adenocarcinoma,” noted Manish A. Shah, MD, of Weill Cornell Medicine in New York City.
He presented a phase III, randomized, double-blind, multicenter study comparing the efficacy and safety of mFOLFOX with or without ADX in patients with untreated HER2-negative gastric or gastroesophageal junction adenocarcinoma.
From September 2015 to May 2017, 432 patients were randomized to receive either mFOLFOX plus ADX (218) or mFOLFOX with placebo (114).
The primary endpoint was overall survival, with secondary endpoints of progression free survival, objective response rate, and safety.
As for statistical assumptions regarding overall survival, “we were aggressive,” said Shah. “We wanted to demonstrate a real improvement in benefit with andecaliximab, so we were hoping to improve overall survival from 11.5 months to 16.4 months.”
However, Shah reported, “disappointingly, we didn’t see an improvement in survival with ADX.”
Overall survival was a median of 12.5 months (95% CI 11.2-14.0), compared to 11.8 months (95% CI 10.3-13.5) in the ADX and placebo groups, respectively (HR 0.93).
Median progression-free survival was 7.5 months compared to 7.1 months in the ADX and placebo groups, respectively (HR 0.84), while the overall response rate was 50.5% vs 41.1% in the ADX and placebo groups, respectively.
Adverse events were comparable in the two groups, with the most frequent being nausea, diarrhea, neutropenia, and fatigue.
Shah did note that elderly patients — 65 and older — did better on ADX than other subgroups. Median overall survival in that group was 13.9 months compared to 10.6 months in the placebo group, while progression-free survival was 8.7 months compared to 6.5 months.
The apparent increased activity of the combination of mFOLFOX with ADX in patients ages 65 or older needs further study, Shah said.
Shah disclosed institutional research funding from Boston Biomedical, Gilead Sciences, Merck, and Oncolys BioPharma.
Ilson disclosed consulting or an advisory role with AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly/ImClone, Merck, Pieris Pharmaceuticals, and Roche/Genentech.