Motolimod plus standard chemotherapy and cetuximab (EXTREME regimen) was well tolerated, but did not lead to improvements in survival outcomes among most patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), according to a study published in JAMA Oncology.1
Previous studies have demonstrated that motolimod — a toll-like receptor 8 (TLR8) agonist — can induce positive immune responses, but whether it could improve outcomes in the first-line setting with the EXTREME regimen among patients with R/M SCCHN has yet to be fully investigated.
For the phase 2 Active8 (ClinicalTrials.gov Identifier: NCT01836029) study, researchers randomly assigned 195 patients to receive the EXTREME regimen (carboplatin or cisplatin, fluorouracil, cetuximab) plus placebo or motolimod every 3 weeks for 6 cycles. Patients continued to receive weekly cetuximab with either placebo or motolimod every 4 weeks thereafter.
Results showed that median progression-free survival (PFS) was 6.1 months among patients treated with motolimod compared with 5.9 months for patients who received placebo (hazard ratio [HR], 0.99; 1-sided 90% CI, 0.00-1.22; P = .47). The median overall survival (OS) was 13.5 months and 11.3 months for motolimod and placebo, respectively (HR, 0.95; 1-sided 90% CI, 0.00-1.22; P = .40).
Patients treated with motolimod had an increased incidence of injection site reactions, pyrexia, chills, anemia, and acneiform rash.
A pre-specified subgroup revealed however, that motolimod significantly prolonged survival outcomes among patients who were human papillomavirus-positive; PFS was 7.8 months compared with 5.9 months among patients treated with placebo (HR, 0.58; 1-sided 90% CI, 0.00-0.90; P = .046) and OS was 15.2 months versus 12.6 months (HR, 0.41; 1-sided 90% CI, 0.00-0.77; P = .03).
In an exploratory analysis, patients who experienced injection site reactions had improved PFS (median PFS, 7.1 vs 5.9 months; HR, 0.69; 1-sided 90% CI, 0.00-0.93; P = .06) and OS (18.7 vs 12.6; HR, 0.56; 1-sided 90% CI, 0.00-0.81; P = .02).
The authors concluded that “results provide important information regarding patient selection for treatment with TLR8 agonists and suggest that further evaluation in HPV-positive oropharyngeal cancer may be warranted.”
- Ferris RL, Saba NF, Gitlitz BJ, et al. Effect of adding motolimod to standard combination chemotherapy and cetuximab treatment of patients with squamous cell carcinoma of the head and neck [published online June 21, 2018]. JAMA Oncol. doi:10.1001/jamaoncol.2018.1888