Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Abstract

Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving a pathologic complete response (pCR) has proven to be inconsistent, and despite treatment, roughly half of patients experience locoregional recurrence or metastasis. Consequently, there has been a paradigm shift towards exploring the potential of immunotherapy in reshaping the landscape of LAEC management. Recent research has particularly focused on immune checkpoint inhibitors, investigating their application in both neoadjuvant and adjuvant settings. These inhibitors, designed to block specific proteins in immune cells, are meant to enhance the immune system’s ability to target and combat cancer cells. Emerging evidence from these studies suggests the possibility of a mortality benefit, indicating that immunotherapy may contribute to improved overall survival rates for individuals grappling with esophageal cancer. This manuscript aims to meticulously review the existing literature surrounding neoadjuvant and adjuvant immunotherapy in the context of LAEC management. The intention is to thoroughly examine the methodologies and findings of relevant studies, providing a comprehensive synthesis of the current understanding of the impact of immunotherapy on esophageal cancer.

Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study

“…MSI-H tumors are known to have a better response [19] when treated with immune checkpoint inhibitors; this might explain part of the achievement of a high pathCR rate in the PANDA trial. That cohort was also favored by the 90% prevalence of patients with a positive PD-L1 result (CPS ≥ 1), thus responding very well to the PD-L1 inhibitor [20], while 35% of our cohort (n = 7/20 patients) had a positive PD-L1 result. A larger randomized controlled clinical trial is necessary to not only reduce biases but to warrant validation of these observed results.…”

“…Immune checkpoint inhibitors have been found to improve OS when added to frontline chemotherapy in patients with advanced esophageal, GEJ, and gastric cancer [20,[23][24][25]. However, the current results from other trials incorporating ICIs in the localized setting, namely Attraction-5 [26] (post-operative approach but relevant to occult disease) and Keynote-585 [27], are mostly not superior.…”

“…Newer ICI agents such as durvalumab and toripalimab have shown encouraging results in gastric and gastroesophageal junction cancers [20,[29][30][31]. Preliminary results from the MATTERHORN (phase 3) trial showed improved pathCR (19% vs. 7%, odds ratio [OR] 3.08; p < 0.00001) when durvalumab was combined with neoadjuvant FLOT versus FLOT alone for resectable gastric and GEJ cancers; EFS and OS results are still forthcoming.…”