Neoadjuvant Immunotherapy in Gastroesophageal Cancer: A Promising Early Signal?

In the article that accompanies this editorial, Lorenzen et al 1 report exploratory efficacy findings, focused on pathologic response, of neoadjuvant immunotherapy-containing chemotherapy in patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma (GEA) in the ongoing DANTE/FLOT8 trial.DANTE is an open-label phase II/III trial (German AIO) in which patients are randomly assigned to receive pre-/post-operative FLOT with atezolizumab versus FLOT alone.To our knowledge, the current article is the first full manuscript, to date, to report efficacy results from a randomized controlled trial (RCT) evaluating the addition of immunotherapy to chemotherapy in the neoadjuvant setting for this disease.The most noteworthy finding is a higher pathologic complete response (pCR) rate in the immunotherapy-containing arm.6][7] Together, these promising results raise the possibility that neoadjuvant immunotherapy-containing treatment in GEA might improve survival, thereby helping address the fourth-highest cause of cancer mortality in the world. 8r resectable disease, a current standard treatment for adenocarcinomas of the stomach/GEJ is perioperative FLOT. 9For adenocarcinomas of the esophagus, a common treatment is neoadjuvant chemoradiation (CRT) followed by surgery and, if residual pathologic disease exists, adjuvant nivolumab. 10,11Regrettably, <60% of patients are alive 3 years later with either approach. 9,12,13e primary end point of DANTE in the original phase II design (N 5 295) was progression-/ disease-free survival (DFS); then, on the basis of encouraging results from immunotherapy trials for advanced-stage disease, the trial was converted to a phase III trial (N 5 556) with a primary end point of event-free survival (EFS).The primary end point of the phase II portion was subsequently modified to surgical pathology response (eg, pCR), with the original phase II end points modified to be exploratory or secondary.The current manuscript reports these surgical pathology data from the phase II portion.Notably, the pCR rate was higher in the atezolizumab-containing arm versus control (eg, ypT0N0 23% v 14%).Differences persisted even when patients who were mismatch repair-deficient (dMMR) were excluded.No new safety signals were identified.