Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial

Oncologist. 2023 Sep 7;28(9):827-e822. doi: 10.1093/oncolo/oyad096.

Abstract

Background: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers.

Methods: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated.

Results: Median PFS was 2.6 months in arm A [90% CL 1.8-3.5] and 2.3 months in arm B [90% 2.0-3.5], P = .86. Stable disease was observed in 29 (33%) patients. Objective response rates for Arms A and B were 12% [90% CI, 5-23%] and 14% [90% CI, 6-25%]. Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56.

Conclusion: The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388).

Keywords: esophageal; gastroesophageal junction; insulin-like growth factor-1 receptor; xixutumumab.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / pathology
  • Esophagogastric Junction / pathology
  • Humans
  • Paclitaxel / adverse effects
  • Stomach Neoplasms* / drug therapy

Substances

  • cixutumumab
  • Paclitaxel
  • Antibodies, Monoclonal, Humanized

Associated data

  • ClinicalTrials.gov/NCT01142388