Metastatic Gastric Cancer: Promising Frontline Trials

Daniel V. Catenacci, MD: The SOLAR study (NCT02322593) was done in Asia and it was evaluating this drug,TAS-118, which is essentially S-1 [tegafur/gimeracil/oteracil]—an oral fluoropyrimidine that is available in Asia and not in North America—in combination with leucovorin. It was used in the first-line setting in combination with oxaliplatin and compared with S-1 plus cisplatin. It was a little bit odd in that they changed the constant, the platinum, where we do know that there is some evidence in randomized studies comparing oxaliplatin and cisplatin that oxaliplatin is certainly better tolerated. Patients may get active therapy for longer. But it may just be more active in the disease. Two variables were changed there, and, ultimately, it was slightly better on the order of less than 1 month improvement in median overall survival. I certainly wouldn’t think it’s a slam dunk, and it doesn’t affect us here in North America that readily because we don’t have access to S-1.

Salah-Eddin Al-Batran, MD: There was a phase 2/3 trial, which compared modified FOLFOX [folinic acid, fluorouracil, oxaliplatin] versus modified FOLFOX plus varlitinib in the first-line treatment of patients with metastatic gastric or gastroesophageal junction adenocarcinoma. This trial consisted of 2 parts. The first part was the phase 2 part, and the primary end point was response rate. Then there was a phase 3 part. I didn’t see results of this trial, but there has been a [news] release saying that the primary end point of the trial was not met. Response rate, in fact, was improved slightly and was around 20% with completion in the experimental arm versus 12% or 13% in the control arm. However, this was not statistically significant.

Kei Muro, MD: SPOTLIGHT (NCT03504397) is a first-line trial in the gastric cancer field. IMAB362 for claudin 18.2–positive gastric cancer already was studied in a randomized phase 2 trial of EOX [epirubicin, capecitabine oxaliplatin] versus EOX plus this agent. It’s clearly beneficial in overall survival and progression-free survival. Now it’s in a randomized phase 3 trial. Claudin 18.2–positive disease occurs in around 50% of gastric cancer [cases]. We hope it is positive in selective patients in the first-line setting for advanced gastric cancer. However, until now, many targeted agents for gastric cancer failed. We would like to expect this trial will have good data results.

Salah-Eddin Al-Batran, MD: The ARMANI trial (NCT02934464) is an interesting trial evaluating switch maintenance for standard chemotherapy with a doublet. The switch maintenance compares continuing chemotherapy, which is the standard arm, or switching to paclitaxel and ramucirumab. This is a phase 3 trial, which is ongoing and still recruiting patients. The primary end point of this trial is progression-free survival, and I think that approximately 280 patients are going to be enrolled in this trial. I think results are expected in a few years.

Transcript edited for clarity.