As reported in the Journal of Clinical Oncology by Manish A. Shah, MD, and colleagues, the phase III GAMMA-1 trial showed no improvement in overall survival with the addition of andecaliximab to modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) in the first-line treatment of HER2-negative gastric or gastroesophageal junction adenocarcinoma.
The monoclonal antibody andecaliximab inhibits matrix metalloproteinase 9, an extracellular enzyme involved in matrix remodeling, tumor growth, and metastases.
Manish A. Shah, MD
In the double-blind trial, 432 patients from sites in 16 countries were randomly assigned between September 2015 and May 2017 to receive andecaliximab at 800 mg (n = 218) or placebo (n = 214) via intravenous infusion on days 1 and 15 of each 28-day cycle, plus mFOLFOX6 given on days 1 and 15 of each 28-day cycle for a total of six cycles, followed by leucovorin and fluorouracil on days 1 and 15 of each 28-day cycle. Random assignment was stratified by Eastern Cooperative Oncology Group performance status, geographic region (Latin America or other countries), and primary tumor site (gastric or gastroesophageal junction). Approximately 94% of all patients had metastatic disease and 66% had gastric cancer. Treatment was given until disease progression or intolerance. The primary endpoint was overall survival on intent-to-treat analysis.
As of May 2019, all patients had discontinued the study and overall survival follow-up was completed. Median overall survival was 12.5 months (95% confidence interval [CI] = 11.2–14.0 months) in the andecaliximab group vs 11.8 months (95% CI = 10.3–3.5 months) in the control group (stratified hazard ratio [HR] = 0.93, 95% CI = 0.74–1.18, P = .56).
Median progression-free survival was 7.5 months vs 7.1 months (stratified HR = 0.84, 95% CI = 0.67–1.04, P = .10). Objective response was observed in 51% vs 41% of patients (odds ratio = 1.47, P = .049), with complete response in 8% vs 5%.
In subgroup analysis, the addition of andecaliximab was associated with prolonged overall survival (HR = 0.64, 95% CI, 0.43–0.96, P = .03) and prolonged progression-free survival (HR = 0.50, 95% CI = 0.34–0.74, P < .001) among patients aged ≥ 65 years, although the 95% confidence intervals and P values were not corrected for multiple comparisons.
The most common grade ≥ 3 adverse events in both the andecaliximab group and control group were decreased absolute neutrophil count (30% vs 29% in the control group), neutropenia (22% vs 27%), decreased white blood cells (13% vs 12%), and decreased lymphocyte count (11% vs 12%). Serious adverse events occurred in 48% vs 51% of patients. Adverse events led to discontinuation of treatment in 4% vs 6%. Death due to adverse events occurred in 13 patients (6%) and 17 patients (8%).
The investigators concluded, “The addition of andecaliximab to mFOLFOX6 did not improve overall survival in unselected patients with untreated HER2-negative gastric or gastroesophageal junction adenocarcinoma.”
Dr. Shah, of Weill Cornell Medicine/NewYork-Presbyterian Hematology/Oncology, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gilead Sciences. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.