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. 2020 Jul 15;126(14):3237-3243. doi: 10.1002/cncr.32929. Epub 2020 May 4.


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.

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.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cetuximab / administration & dosage*
  • Drug Resistance, Neoplasm / drug effects*
  • ErbB Receptors / antagonists & inhibitors
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage*
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors


  • Antineoplastic Agents, Immunological
  • Protein Kinase Inhibitors
  • temsirolimus
  • MTOR protein, human
  • EGFR protein, human
  • ErbB Receptors
  • TOR Serine-Threonine Kinases
  • Cetuximab
  • Sirolimus