Top Line: Does the addition of immunotherapy to perioperative chemo improve outcomes for locally advanced adenocarcinoma of the stomach or EG junction?
The Study: KEYNOTE-585 was a randomized, phase 3 trial that sought to determine if adding pembrolizumab to perioperative chemotherapy improves treatment outcomes for locally advanced gastric or esophago-gastric adenocarcinoma. Just over 1000 patients were enrolled of whom 80% received cisplatin and capecitabine or fluorouracil +/- pembro. A smaller cohort received FLOT +/- pembro. Systemic therapy was given in 3 cycles before and 3 cycles after surgery followed by maintenance pembro. Most had purely gastric cancer (79%), but Siewert 2 and 3 tumors were also allowed. The pathologic complete response rate was significantly higher with the addition of pembro to cis/5FU (12.9% v 2%), and rates were similar in the FLOT cohort. However, this did not translate into a significant improvement in event free survival (median 44.4 v 25.3 months). The rate of EFS at 24 months was 58% with pembro and 51% without. Likewise, there was no improvement in median OS with pembro (60.7 v 58 months). While perioperative chemo is pretty standard for gastric cancer, its main rival is chemoradiation plus nivolumab at the EG junction. In the Neo-AEGIS trial, perioperative chemo (including FLOT) wasn’t superior to neoadjuvant chemoradiation. In that trial, pCR rates were superior with CRT and similar to the rate seen in this trial with pembro. Also recall that in CheckMate 577 adding adjuvant nivo for patients with residual disease after chemoradiation for esophageal and EG junction cancer improved disease free survival. These are apples to oranges comparisons, but when debating management of EG junction tumors, adding pembro didn’t significantly improve outcomes of perioperative chemotherapy.
TBL:In KEYNOTE-585, adding concurrent and maintenance pembrolizumab to perioperative chemotherapy for locally advanced gastric or EG junction cancer didn’t significantly improve event free survival. | Shitara, Lancet Oncol 2023
The Study: KEYNOTE-585 was a randomized, phase 3 trial that sought to determine if adding pembrolizumab to perioperative chemotherapy improves treatment outcomes for locally advanced gastric or esophago-gastric adenocarcinoma. Just over 1000 patients were enrolled of whom 80% received cisplatin and capecitabine or fluorouracil +/- pembro. A smaller cohort received FLOT +/- pembro. Systemic therapy was given in 3 cycles before and 3 cycles after surgery followed by maintenance pembro. Most had purely gastric cancer (79%), but Siewert 2 and 3 tumors were also allowed. The pathologic complete response rate was significantly higher with the addition of pembro to cis/5FU (12.9% v 2%), and rates were similar in the FLOT cohort. However, this did not translate into a significant improvement in event free survival (median 44.4 v 25.3 months). The rate of EFS at 24 months was 58% with pembro and 51% without. Likewise, there was no improvement in median OS with pembro (60.7 v 58 months). While perioperative chemo is pretty standard for gastric cancer, its main rival is chemoradiation plus nivolumab at the EG junction. In the Neo-AEGIS trial, perioperative chemo (including FLOT) wasn’t superior to neoadjuvant chemoradiation. In that trial, pCR rates were superior with CRT and similar to the rate seen in this trial with pembro. Also recall that in CheckMate 577 adding adjuvant nivo for patients with residual disease after chemoradiation for esophageal and EG junction cancer improved disease free survival. These are apples to oranges comparisons, but when debating management of EG junction tumors, adding pembro didn’t significantly improve outcomes of perioperative chemotherapy.
TBL:In KEYNOTE-585, adding concurrent and maintenance pembrolizumab to perioperative chemotherapy for locally advanced gastric or EG junction cancer didn’t significantly improve event free survival. | Shitara, Lancet Oncol 2023