A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab-resistant head and neck cancer: The MAESTRO study

Tanguy Y. Seiwert, Sara Kochanny, Kevin Wood, Francis P. Worden, Douglas Adkins, James L. Wade, Bethany G. Sleckman, Daniel Anderson, Ryan J. Brisson, Theodore Karrison, Walter M. Stadler, Everett E. Vokes*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Patients with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) have poor outcomes. This study hypothesized that dual blockade of mammalian target of rapamycin and epidermal growth factor receptor (EGFR) would overcome cetuximab resistance on the basis of the role of phosphoinositide 3-kinase signaling in preclinical models of EGFR resistance. Methods: In this multicenter, randomized clinical study, patients with recurrent/metastatic HNSCC with documented progression on cetuximab (in any line in the recurrent/metastatic setting) received 25 mg of temsirolimus weekly plus cetuximab at 400/250 mg/m2 weekly (TC) or single-agent temsirolimus (T). The primary outcome was progression-free survival (PFS) in the TC arm versus the T arm. Response rates, overall survival, and toxicity were secondary outcomes. Results: Eighty patients were randomized to therapy with TC or T alone. There was no difference for the primary outcome of median PFS (TC arm, 3.5 months; T arm, 3.5 months). The response rate was 12.5% in the TC arm (5 responses, including 1 complete response [2.5%]) and 2.5% in the T arm (1 partial response; P =.10). Responses were clinically meaningful in the TC arm (range, 3.6-9.1 months) but not in the T-alone arm (1.9 months). Fatigue, electrolyte abnormalities, and leukopenia were the most common grade 3 or higher adverse events and occurred in less than 20% of patients in both arms. Conclusions: The study did not meet its primary endpoint of improvement in PFS. However, TC induced responses in cetuximab-refractory patients with good tolerability. The post hoc observation of activity in patients with acquired resistance (after prior benefit from cetuximab monotherapy) may warrant further investigation.

Original languageEnglish (US)
Pages (from-to)3237-3243
Number of pages7
JournalCancer
Volume126
Issue number14
DOIs
StatePublished - Jul 15 2020
Externally publishedYes

Keywords

  • cetuximab
  • erbB-1
  • local genes
  • neoplasm metastasis
  • neoplasm recurrence
  • squamous cell carcinoma of head and neck
  • target of rapamycin (TOR) serine-threonine kinases
  • temsirolimus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab-resistant head and neck cancer: The MAESTRO study'. Together they form a unique fingerprint.

  • Cite this

    Seiwert, T. Y., Kochanny, S., Wood, K., Worden, F. P., Adkins, D., Wade, J. L., Sleckman, B. G., Anderson, D., Brisson, R. J., Karrison, T., Stadler, W. M., & Vokes, E. E. (2020). A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab-resistant head and neck cancer: The MAESTRO study. Cancer, 126(14), 3237-3243. https://doi.org/10.1002/cncr.32929