The Benefits of Adjuvant Trastuzumab for HER-2-Positive Salivary Gland Cancers

Glenn J. Hanna*, Ji Eun Bae, Jochen H. Lorch, Robert I. Haddad, Vickie Y. Jo, Jonathan D. Schoenfeld, Danielle N. Margalit, Roy B. Tishler, Laura A. Goguen, Donald J. Annino, Nicole G. Chau

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Although high-grade salivary gland cancers (SGCs) often express androgen receptor (AR) and/or HER-2/neu, therapeutically targeting these receptors in SGC remains investigational. We investigated the prevalence of receptor expression and the benefit of adjuvant HER-2 directed therapy in the high-risk postoperative setting and explored the clinical utility of sequentially targeting these receptors in the setting of advanced disease. Materials and Methods: We clinically annotated 95 patients with SGC (excluding adenoid cystic carcinoma) treated at our institution from 2002 to 2019 and recorded AR, HER-2/neu status, and tumor genomic profiling results when available. Clinicopathologic information was then integrated with outcomes. Results: Of 95 patients, most had high-risk histologies, with salivary duct carcinoma (SDC) as the most frequent diagnosis (43, 45%). Thirty-five (37%) experienced recurrence (51% SDC). HER-2/neu was positive (1–3+) by immunostaining in 34 of 52 (65%) evaluable cases. There was no difference in survival based on HER-2/neu or AR expression. Nine of 17 (53%) patients with HER-2+ SDC received adjuvant chemoradiation with trastuzumab. Median disease-free survival (DFS) and overall survival (OS) were longer among patients with HER-2/neu 3+ staining tumors who received adjuvant trastuzumab versus those who did not (DFS, 117 vs. 9 months; p =.02; OS, 74 vs. 43 months; p =.02), with no difference among other HER-2/neu subgroups (0–2+). Two of nine (22%) patients treated with adjuvant trastuzumab demonstrated recurrence, both with low HER-2/neu staining intensity (1+). Longer time to recurrence (hazard ratio, 0.94; p =.01) predicted improved outcomes. Both androgen deprivation and HER-2-directed therapies had clinical benefit beyond the first-line metastatic setting, with partial response observed beyond second-line use. Conclusion: Although prospective data are lacking, the use of adjuvant trastuzumab in high-risk patients with SGC appears beneficial, particularly among patients with tumors exhibiting HER-2/neu 3+ immunostaining. Implications for Practice: Results of this study showed an improved disease-free and overall survival in patients treated with adjuvant trastuzumab for high-risk salivary gland cancers with strong HER-2/neu staining intensity. Following recurrence or metastatic spread, sequential HER-2, and androgen-directed therapies may benefit certain patients with salivary gland cancer.

Original languageEnglish (US)
Pages (from-to)598-608
Number of pages11
JournalOncologist
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2020
Externally publishedYes

Keywords

  • Adjuvant therapy
  • HER-2/neu
  • Outcomes
  • Salivary gland cancer
  • Survival
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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