Metastatic Gastric Cancer: Promising Second-Line Trials

Salah-Eddin Al-Batran, MD: The phase 1/2 nivolumab/paclitaxel/ramucirumab trial is a 1-arm trial that was conducted to evaluate the role of combining the efficacious second-line regimen, ramucirumab plus paclitaxel with a checkpoint inhibitor, nivolumab. In this trial, patients were stratified either to be PD-L1 overexpressors or PD-L1-negative. This trial was a 2-part trial; overall, approximately 43 patients were enrolled. The primary end point was 6-month, progression-free survival. This primary end point with this combination in the overall population was 46%, which is pretty good.

Interestingly, there was a very encouraging response rate. The response rate was 37% in the overall population with this combination. Overall survival was also encouraging, as median overall survival was roughly 14 months in this cohort.Interestingly, when you look at the PD-L positive population, all these results were better in this population. It’s a signal-providing trial, and I think that the overall conclusion is that this regimen clearly deserves further investigation.

Daniel V. Catenacci, MD: With respect to the second-line FRUTIGA study, which is a fruquintinib second-line study randomizing patients to this antiangiogenesis tyrosine kinase inhibitor, randomizing them to paclitaxel…It is a study coming out of China, a phase 3 study that has not yet reported results. This is 1 of many studies that are coming out with tyrosine kinase inhibitors, some of which have already reported out in the third-line setting, that we can talk about. This study is moving to second-line setting. My thoughts on it are that we do know that paclitaxel plus ramucirumab was the standard option at this point, based on the RAINBOW study that was reported in 2014.

This study, even if it does show benefit compared with paclitaxel, we note that the control arm is an inferior control arm with just paclitaxel alone without paclitaxel and ramucirumab. In my opinion, it is not really moving the needle forward even if paclitaxel plus this tyrosine kinase inhibitor is better than paclitaxel alone. My sense is that it might have worse toxicities than say paclitaxel plus ramucirumab, a monoclonal antibody targeting VEGFR2. We will see the data, but ultimately I think that this will not be practice-changing, even if it is “positive” coming out of a Chinese-only population with the other caveats that I’ve mentioned.

Kei Muro, MD: KEYNOTE-061 trial is a global trial for advanced gastric cancer in second-line setting. Paclitaxel versus pembro [pembrolizumab] monotherapy, open-label trial. It unfortunately failed overall survival benefit and progression-free survival as a primary end point in advanced gastric cancer in second-line setting.

KEYNOTE-063 is an only Asian trial…. Korea, China, Taiwan, and Malaysia populations are gathered in this trial. It is very similar to the study design of KEYNOTE-061 trial. I also hope this data shows benefit in overall survival in second-line setting.

Salah-Eddin Al-Batran, MDis a phase 2 trial evaluating the role of the combination of irinotecan and regorafenib in the treatment of patients with metastatic gastric cancer in the second-line setting.

This is, in fact, a trial in progress. This trial is a phase 2 trial that contains 154 patients, and patients will receive a combination of irinotecan and nivolumab. The primary end point is overall survival, but we still are waiting for results.

Transcript edited for clarity.