TY - JOUR
T1 - Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas
T2 - A Phase I/II Single-Arm Study
AU - Sewastjanow-Silva, Matheus
AU - Xiao, Lianchun
AU - Gonzalez, Graciela N.
AU - Wang, Xuemei
AU - Hofstetter, Wayne
AU - Swisher, Stephen
AU - Mehran, Reza
AU - Sepesi, Boris
AU - Bhutani, Manoop S.
AU - Weston, Brian
AU - Coronel, Emmanuel
AU - Waters, Rebecca E.
AU - Rogers, Jane E.
AU - Smith, Jackie
AU - Lyons, Larry
AU - Reilly, Norelle
AU - Yao, James C.
AU - Ajani, Jaffer A.
AU - Murphy, Mariela Blum
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - NCT03784326
KW - adenocarcinoma
KW - atezolizumab
KW - esophagus
KW - gastroesophageal junction
KW - immunotherapy
KW - trial
UR - http://www.scopus.com/inward/record.url?scp=85190115885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85190115885&partnerID=8YFLogxK
U2 - 10.3390/cancers16071378
DO - 10.3390/cancers16071378
M3 - Article
C2 - 38611056
AN - SCOPUS:85190115885
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 7
M1 - 1378
ER -