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. 2024 Mar 31;16(7):1378.
doi: 10.3390/cancers16071378.

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

Matheus Sewastjanow-Silva  1 , Lianchun Xiao  2 , Graciela N Gonzalez  2 , Xuemei Wang  2 , Wayne Hofstetter  3 , Stephen Swisher  3 , Reza Mehran  3 , Boris Sepesi  3 , Manoop S Bhutani  4 , Brian Weston  4 , Emmanuel Coronel  4 , Rebecca E Waters  5 , Jane E Rogers  6 , Jackie Smith  1 , Larry Lyons  7 , Norelle Reilly  7 , James C Yao  1 , Jaffer A Ajani  1 , Mariela Blum Murphy  1
Affiliations

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

Matheus Sewastjanow-Silva et al. Cancers (Basel). .

Abstract

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24-31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.

Keywords: NCT03784326; adenocarcinoma; atezolizumab; esophagus; gastroesophageal junction; immunotherapy; trial.

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Conflict of interest statement

The University of Texas MDACC has received Research Grants on behalf of Jaffer Ajani from the following: BMS, Merck, Astellas, Taiho, Delta Fly, Roche, Prolinx, Zymeworks, Daiichi, Leap, Gilead, and LaNova. Jaffer Ajani is a self-paid ad hoc consultant for the following: BMS, Merck, Astellas, Taiho, More, Zymeworks, Beigene, Dava, Astrazeneca, Acrotech, Daiichi, Vaccinogen, Innovent, Merck Serrono, Oncotherics, Bayer, OncLive, FivePrime, Amgen, GRAIL, Novartis, Geneos, Arcus, Servier, BI, and Gilead. Larry Lyons as employed by the company Genentech Inc. All other authors have no conflicts of interest related to this manuscript.

Figures

Figure 1
Figure 1
Summary of treatment regimen. Created at Biorender.com on 20 October 2023.
Figure 2
Figure 2
Kaplan–Meier curves for overall survival and disease-free survival. Median overall survival: 38.6 months (95% CI: 30.5, NA); median disease-free survival: 28.8 months (95% CI: 14.7, NA).
See this image and copyright information in PMC

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