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Adding andecaliximab (ADX) to first-line treatment with modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) provided no survival benefit in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in the phase 3 GAMMA-1 study.

Objective response rates were 50.5% in the ADX arm and 41.1% in the placebo arm (stratified odds ratio, 1.47; P = .049), but this did not translate to improved survival.

The median overall survival (OS) was 12.5 months in the ADX arm and 11.8 months in the placebo arm (stratified hazard ratio, 0.93; P = .56). The median progression-free survival (PFS) was 7.5 months and 7.1 months, respectively (stratified HR, 0.84; P = .10).

Manish A. Shah, MD, of Weill Cornell Medicine, New York, and colleagues reported these results in the Journal of Clinical Oncology.

The lack of improvement when ADX was added to mFOLFOX6 was despite encouraging antitumor activity seen with the combination in a phase 1 and phase 1b study, the authors noted.

“Despite compelling early-phase data, the addition of ADX did not improve outcomes in an unselected patient population,” the authors wrote. “Tissue or blood samples were not available for correlative analyses to understand why ADX was less active than expected or to identify any gastric cancer subset that may derive greater benefit with ADX.”

The researchers did note, however, that subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older.
 

Study details

Participants in the double-blind GAMMA-1 trial were adults with confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. They were enrolled at 132 centers worldwide between Oct. 13, 2015, and May 15, 2019.

There were 432 patients randomized to receive mFOLFOX6 plus either 800 mg of ADX (n = 218) or placebo (n = 214) infused on days 1 and 15 of each 28-day cycle until disease progression or intolerance.

As noted before, there was a significant improvement in response rate with the addition of ADX (P = .049) but no significant improvements in PFS (P = .10) or OS (P = .56).

On the other hand, subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older. The authors said this result is intriguing and warrants further study.

Among patients aged 65 and older, the median OS was 13.9 months in the ADX arm and 10.5 months in the placebo arm (stratified HR, 0.64; P = .03). The median PFS was 8.7 months and 5.6 months, respectively (stratified HR, 0.50; P < .001). However, the P values were not adjusted for multiplicity.

No significant differences were seen between the groups with respect to safety outcomes. Serious adverse events occurred in 47.7% of patients in the ADX arm and 51.4% of those in the placebo arm. Nine patients in the ADX arm and 13 in the placebo arm discontinued the study because of adverse events.

The GAMMA-1 trial was sponsored by Gilead Sciences. The authors disclosed relationships with Gilead and many other companies.

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Adding andecaliximab (ADX) to first-line treatment with modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) provided no survival benefit in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in the phase 3 GAMMA-1 study.

Objective response rates were 50.5% in the ADX arm and 41.1% in the placebo arm (stratified odds ratio, 1.47; P = .049), but this did not translate to improved survival.

The median overall survival (OS) was 12.5 months in the ADX arm and 11.8 months in the placebo arm (stratified hazard ratio, 0.93; P = .56). The median progression-free survival (PFS) was 7.5 months and 7.1 months, respectively (stratified HR, 0.84; P = .10).

Manish A. Shah, MD, of Weill Cornell Medicine, New York, and colleagues reported these results in the Journal of Clinical Oncology.

The lack of improvement when ADX was added to mFOLFOX6 was despite encouraging antitumor activity seen with the combination in a phase 1 and phase 1b study, the authors noted.

“Despite compelling early-phase data, the addition of ADX did not improve outcomes in an unselected patient population,” the authors wrote. “Tissue or blood samples were not available for correlative analyses to understand why ADX was less active than expected or to identify any gastric cancer subset that may derive greater benefit with ADX.”

The researchers did note, however, that subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older.
 

Study details

Participants in the double-blind GAMMA-1 trial were adults with confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. They were enrolled at 132 centers worldwide between Oct. 13, 2015, and May 15, 2019.

There were 432 patients randomized to receive mFOLFOX6 plus either 800 mg of ADX (n = 218) or placebo (n = 214) infused on days 1 and 15 of each 28-day cycle until disease progression or intolerance.

As noted before, there was a significant improvement in response rate with the addition of ADX (P = .049) but no significant improvements in PFS (P = .10) or OS (P = .56).

On the other hand, subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older. The authors said this result is intriguing and warrants further study.

Among patients aged 65 and older, the median OS was 13.9 months in the ADX arm and 10.5 months in the placebo arm (stratified HR, 0.64; P = .03). The median PFS was 8.7 months and 5.6 months, respectively (stratified HR, 0.50; P < .001). However, the P values were not adjusted for multiplicity.

No significant differences were seen between the groups with respect to safety outcomes. Serious adverse events occurred in 47.7% of patients in the ADX arm and 51.4% of those in the placebo arm. Nine patients in the ADX arm and 13 in the placebo arm discontinued the study because of adverse events.

The GAMMA-1 trial was sponsored by Gilead Sciences. The authors disclosed relationships with Gilead and many other companies.

Adding andecaliximab (ADX) to first-line treatment with modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) provided no survival benefit in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in the phase 3 GAMMA-1 study.

Objective response rates were 50.5% in the ADX arm and 41.1% in the placebo arm (stratified odds ratio, 1.47; P = .049), but this did not translate to improved survival.

The median overall survival (OS) was 12.5 months in the ADX arm and 11.8 months in the placebo arm (stratified hazard ratio, 0.93; P = .56). The median progression-free survival (PFS) was 7.5 months and 7.1 months, respectively (stratified HR, 0.84; P = .10).

Manish A. Shah, MD, of Weill Cornell Medicine, New York, and colleagues reported these results in the Journal of Clinical Oncology.

The lack of improvement when ADX was added to mFOLFOX6 was despite encouraging antitumor activity seen with the combination in a phase 1 and phase 1b study, the authors noted.

“Despite compelling early-phase data, the addition of ADX did not improve outcomes in an unselected patient population,” the authors wrote. “Tissue or blood samples were not available for correlative analyses to understand why ADX was less active than expected or to identify any gastric cancer subset that may derive greater benefit with ADX.”

The researchers did note, however, that subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older.
 

Study details

Participants in the double-blind GAMMA-1 trial were adults with confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. They were enrolled at 132 centers worldwide between Oct. 13, 2015, and May 15, 2019.

There were 432 patients randomized to receive mFOLFOX6 plus either 800 mg of ADX (n = 218) or placebo (n = 214) infused on days 1 and 15 of each 28-day cycle until disease progression or intolerance.

As noted before, there was a significant improvement in response rate with the addition of ADX (P = .049) but no significant improvements in PFS (P = .10) or OS (P = .56).

On the other hand, subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older. The authors said this result is intriguing and warrants further study.

Among patients aged 65 and older, the median OS was 13.9 months in the ADX arm and 10.5 months in the placebo arm (stratified HR, 0.64; P = .03). The median PFS was 8.7 months and 5.6 months, respectively (stratified HR, 0.50; P < .001). However, the P values were not adjusted for multiplicity.

No significant differences were seen between the groups with respect to safety outcomes. Serious adverse events occurred in 47.7% of patients in the ADX arm and 51.4% of those in the placebo arm. Nine patients in the ADX arm and 13 in the placebo arm discontinued the study because of adverse events.

The GAMMA-1 trial was sponsored by Gilead Sciences. The authors disclosed relationships with Gilead and many other companies.

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