REO 018 was a randomized, double-blind, two-arm, multi-center trial of REOLYSIN® in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, or squamous cell cancer of the nasopharynx, who had progressed on or after prior platinum-based chemotherapy. Patients received paclitaxel and carboplatin on day 1 of each twenty-one day cycle, with either REOLYSIN® (test arm) or placebo (control arm) administered on days 1 through 5. The trial enrolled a total of 167 patients segregated into two patient groups: patients with local recurrent disease, with or without distal metastases, and those with only distal metastases. The primary objective was overall survival. Secondary objectives were progression-free survival, objective response rate (complete response (CR) plus partial response (PR)) and duration, safety and tolerability, and best percentage tumour-specific response in loco-regional and metastatic disease.
In December 2012, Oncolytics announced positive top-line data examining initial percentage tumour changes between the pre-treatment and first post-treatment scans (typically performed at six weeks post-first treatment) of all patients enrolled in the study. Of the 105 total patients with evaluable metastatic tumours, 86% (n=50) of those in the test arm of the study exhibited tumour stabilization (defined as zero percent growth only) or shrinkage, compared with 67% of patients (n=55) in the control arm. This was statistically significant, with a p-value of 0.025. The analysis also showed that REOLYSIN® in combination with carboplatin and paclitaxel was statistically significantly better than carboplatin and paclitaxel alone at stabilizing or shrinking metastatic tumours, yielding a p-value of 0.03.
In April 2014, the Company announced detailed results from the study. One hundred and eighteen patients had loco-regional disease, with or without distal metastases. Under the study conditions, test arm patients with loco-regional disease demonstrated a progression-free survival (PFS) benefit over control arm patients through five cycles of therapy. An intent-to-treat analysis of this study population showed a statistically significant improvement in PFS for the test arm versus the control arm (p=0.0072, hazard ratio=0.5360) using Type II censoring from the median PFS in each arm (48 days in the control arm and 95 days in the test arm). An intent-to-treat analysis of the patients with loco-regional disease to the median PFS in each arm also demonstrated a statistically significant improvement in overall survival (OS) for the test arm versus the control arm (p=0.0146, hazard ratio=0.5099), censoring any patients who received post-discontinuation therapy at the date on which they commenced the first of these therapies. The 118 patients with loco-regional disease, with or without distal metastases, were evaluated for percentage magnitude of tumour shrinkage at the first post-treatment scan (performed at approximately six weeks). The test arm showed a statistical trend towards increased tumour shrinkage over the control arm (p=0.076).
In the April 2014 analysis, there were an additional 47 patients with distal metastases alone, eight of whom remained alive at the time of the analysis. Test arm patients with distal metastases alone showed a PFS benefit over control arm patients through five cycles of therapy; however, there were too few patients to power a statistical analysis of the PFS and OS of this patient group. The 47 patients with distal metastases alone were evaluated for percentage magnitude of tumour shrinkage at the first post-treatment scan (performed at approximately six weeks). The test arm demonstrated statistically significant increased tumour shrinkage over the control arm (p=0.021).
REOLYSIN® was found to be safe and well-tolerated by patients. Patients on the test arm of the study experienced a higher incidence of flu-like symptoms consistent with those noted in earlier clinical studies of REOLYSIN® and treatment with a virus, most commonly mild fever, chills, nausea and diarrhea. Fewer patients required dose reductions of paclitaxel due to neuropathy or neurotoxicity on the test arm than the control arm (zero in the test arm versus six in the control arm; p=0.028); on this basis, the Company intends to explore the potential chemoprotective and neuroprotective properties of REOLYSIN® in future clinical studies.