Results of a Randomized Phase IIb Trial of Nelipepimut-S þ Trastuzumab versus Trastuzumab to Prevent Recurrences in Patients with High-Risk HER2 Low-Expressing Breast Cancer

G. Travis Clifton, Diane Hale, Timothy J. Vreeland, Annelies T. Hickerson, Jennifer K. Litton, Gheath Alatrash, Rashmi K. Murthy, Na Qiao, Anne V. Philips, Jason J. Lukas, Jarrod P. Holmes, George E. Peoples, Elizabeth A. Mittendorf

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Purpose: Preclinical data provide evidence for synergism between HER2-targeted peptide vaccines and trastuzumab. The efficacy of this combination was evaluated in patients with HER2 low-expressing breast cancer in the adjuvant setting. Patients and Methods: A phase IIb, multicenter, randomized, single-blinded, controlled trial enrolled disease-free patients after standard therapy completion (NCT01570036). Eligible patients were HLA-A2, A3, A24, and/or A26þ, and had HER2 IHC 1þ/2þ, FISH nonamplified breast cancer, that was node positive and/or hormone receptor–negative [triple-negative breast cancer (TNBC)]. Patients received trastuzumab for 1 year and were randomized to placebo (GM-CSF, control) or nelipepimut-S (NPS) with GM-CSF. Primary outcome was 24-month disease-free survival (DFS). Secondary outcomes were 36-month DFS, safety, and immunologic response. Results: Overall, 275 patients were randomized; 136 received NPS with GM-CSF, and 139 received placebo with GM-CSF. There were no clinicopathologic differences between groups. Concurrent trastuzumab and NPS with GM-CSF was safe with no additional overall or cardiac toxicity compared with control. At median followup of 25.7 (interquartile range, 18.4–32.7) months, estimated DFS did not significantly differ between NPS and control [HR, 0.62; 95% confidence interval (CI), 0.31–1.25; P ¼ 0.18]. In a planned exploratory analysis of patients with TNBC, DFS was improved for NPS versus control (HR, 0.26; 95% CI, 0.08–0.81, P ¼ 0.01). Conclusions: The combination of NPS with trastuzumab is safe. In HER2 low-expressing breast cancer, no significant difference in DFS was seen in the intention-to-treat analysis; however, significant clinical benefit was seen in patients with TNBC. These findings warrant further investigation in a phase III randomized trial.

Original languageEnglish (US)
Pages (from-to)2515-2523
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number11
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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