| General information |
| Database: | DB00386 |
| Objective: | A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit. |
| Authors: | Gilbert J, et al |
| Title: | A randomizedphase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma. |
| Journal: | Oral Oncol. |
| Year: | 2015 |
| PMID: | 25593015 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab and sorafenib
|
| Target: | NA
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | cetuximab + sorafenib |
| Study Type: | blinded, randomizedphase II, placebo controlled study |
| Key Patients Feature: | Eligible patients included those 18 years of age or older withrecurrent, refractory or metastatic, incurable HNSCC of the oralcavity, oropharynx, larynx, hypopharynx, paranasal sinus, unknown primary or nasopharyngeal carcinoma World HealthOrganization Type 1 (keratinizing, well differentiated). Patientshad an Eastern Cooperative Oncology Group (ECOG) PerformanceStatus (PS) of 0-2 and may have received up to one prior palliativechemotherapy regimen for recurrent, refractory or metastaticHNSCC. Chemotherapy given as part of a regimen for curative intent for recurrent disease did not count as ''prior chemotherapy.¡¯¡¯Patients must not presently be candidates for curative therapy. Ifprimary therapy was given for curative intent, at least 4 weeksmust have elapsed after completion of primary therapy prior toenrollment on this clinical trial. however, toxicities from priortreatment must have resolved to grade 1 or less. |
| Biomarker: | Tumor p16 and HPV status, and plasma immunomodulatory cytokine levels |
| Biomark Analysis: | The p16negative patients had significantly better PFS compared to the p16positive patients (3.7 vs. 1.6months; pvalue: 0.03), regardless of study arms. Twentyfour plasma samples were tested for 12 cytokine levels and patients with higher TGF¦Â1 levels had inferior PFS compared to lotheyr levels (1.9 vs. 4.7months; adjusted pvalue: 0.015), regardless of study arms. |
| Control Group Info: | A: cetuximab without sorafenib B: cetuximab with sorafenib |
| Treatment Info: | R/M HNSCC patients were treated with cetuximab 400mg/m(2) IV on day 1 followed by 250mg/m(2) IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400mg PO twiceaday (Arm B). Each cycle was 21days. |
| Primary End Point: | PFS; evaluations of RR, OS, and toxicities. |
| Secondary End Point: | NA |
| Patients Number: | 55 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The observed clinical benefit, defined as sum of stable disease, minimal response and partial response, was 12% in each arm. The median OS was 9 months in the cetuximab arm and 5.7 months in the combination arm [p=0.41, 95% Confidence Interval (CI) 5.2-12.9 months and 4.2-10.8 months, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3 months in the cetuximab arm and 3.2 months in the combination arm (p = 0.87, 95% CI 1.9- 5.0 months and 1.8-4.2 months, respectively) |
| Median OS A vs. C: | 9 months in the cetuximab arm and 5.7 months in the combination arm [p = 0.41, 95% Confidence Interval (CI) 5.2-12.9 months and 4.2-10.8 months, respectively] |
| Adverse Event(agent arm): | Overall, the regimen was well tolerated. Maculopapular rash was the most common toxicity in both arms; however, only one patient in each arm experienced grade 3 rash while the remaining rash grades were 1 or 2. Fatigue was the second most common toxicity in both arms, with 8 patients in Arm A (7 of which were grade 1 and 2) and 24 patients in Arm B (22 of which were grade 1 and 2). Overall, more grade 3 and 4 toxicities occurred in Arm B than in Arm A, though these were still relatively infrequent on both arms |
| Conclusions: | A subset of RM patients with p16negative tumors or lotheyr plasma TGF¦Â1 levels had longer PFS given the cetuximabbased therapy. Hotheyver, both arms showed only modest response and sorafenib given with cetuximab did not demonstrate clinical benefit. |