. RT (60C66 Gy over 6C7 weeks) concurrent with weekly cisplatin 30 mg/m2 and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). Results Forty-six individuals were accrued; 44 were evaluable and were analyzed. The median follow-up for individuals without recurrence was 49 weeks (range 12C90 weeks). The probability of 2-yr PFS was 70% (95% CI = 58%C85%), and the probability of 2-yr OS was 72% (95% CI = 60%C87%). Fourteen individuals developed recurrent disease, and 13 (30%) of them died. An additional five individuals died from causes other than HNSCC. Treprostinil Severe (grade 3 or higher) toxicities occurred in 14 individuals (32%). Conclusions Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is definitely tolerable and demonstrates improved medical Mouse monoclonal to TLR2 end result for high-risk, resected, HPV-negative HNSCC individuals. Further targeted monoclonal antibody mixtures are warranted. Registered medical trial number “type”:”clinical-trial”,”attrs”:”text”:”NCT00798655″,”term_id”:”NCT00798655″NCT00798655 = 44) 0.0001. The 3-yr PFS was 68% (90% CI = 57%C81%)/(95% CI = 55%C83%). Median PFS was not reached for this trial. Open in a separate window Number 1. KaplanCMeier curves showing (A) progression-free survival and (B) overall survival in weeks. secondary endpoints The estimated probability of 2-yr OS was 72% (CI 60%C87%; Number ?Number1B).1B). The 3-yr OS was 65% (90% CI = 54%C78%)/(95% CI = 52%C81%), with median OS not reached. At time of study completion, a total of 18 individuals experienced died, 13 from disease and 5 from other causes. These included liver cirrhosis, pneumonia/bacteremia, COPD and cardiopulmonary arrest, happening between 24 and 56 weeks after completion of therapy. security Treatment-related toxicities are summarized in Table ?Table2.2. Overall, 14 individuals (32%) experienced grade 3 toxicity. Five individuals (11%) required delay in RT, and 2 individuals (5%) did not complete RT due to adverse events (mucositis). No treatment-related deaths were reported. The most common grade 4 toxicities were lymphopenia (18%) and mucositis (5%). One individual was hospitalized for psychosis, which is not known to be a direct side-effect of panitumumab, and was able to complete radiation. Gastrostomy tube placement was performed prophylactically prior to chemoradiotherapy (CRT) in 19 individuals (43%), and 8 additional individuals (18%) required placement during adjuvant therapy. Of the total 37 (84%) individuals who experienced gastrostomy tube placed, only 3 (7%) required feeling tube long term ( 1 year). Table 2 Marks 3 and 4 toxicities of 44 individuals accrued to the trial = 0.06). Patient serum levels of two epidermal growth-factor receptor ligands, EGF and TGF- were measured by ELISA at baseline and 8 weeks post-panitumumab-chemoradiation in 20 (45%) individuals. There were no changes in serum levels of these cytokines from baseline to week 8. discussion This study was designed to evaluate the effectiveness and safety of the addition of the EGFR-targeting mAb panitumumab to the standard adjuvant cisplatin CRT in individuals with high-risk, resected, HPV-negative HNSCC. Individuals with these features on pathology were shown to benefit from the addition of cisplatin to adjuvant RT, as shown by EORTC trial 22931 and RTOG trial 9501 [3, 4, 12]. Despite improved locoregional control and disease-free survival for individuals with high-risk HNSCC treated with RT plus cisplatin compared with adjuvant RT Treprostinil only, there remains a need for further therapy intensification given the high risk of recurrence, particularly in individuals with HPV-negative disease. Focusing on the EGFR pathway, such as with panitumumab, has been an area of interest for multimodal therapy given 80%C90% overexpression of this protein in HNSCC . The primary endpoint of this phase II trial was PFS at 2 years, and this study was designed and powered to investigate whether 2-yr PFS could be improved by the addition of panitumumab compared with historical settings. We specifically hypothesized that adding panitumumab would increase the 2-yr probability of PFS to 70%, assuming that the control 2-yr PFS for postoperative RT and cisplatin only was 50% (the approximate 2-yr PFS in RTOG 9501 was 55% at 2 yr and 50% at 3 years) . Forty-three individuals were required to have sufficient power to detect this difference. Forty-six individuals were accrued, 44 of whom were evaluable for response. The Treprostinil probability of PFS at 2 years was 70% (95% CI 58C85) and at 3 years PFS was 68% (90% CI = 57%C81%)/(95% CI = 55%C83%). The probability of 2-yr OS, a secondary endpoint, was 72% (95% CI 60%C87%). The 3-yr OS was 65% (90% CI = 54%C78%)/(95% CI = 52%C81%). Neither median PFS nor OS were reached for this trial. Our results suggest that intensification of adjuvant therapy by the addition of panitumumab, a monoclonal antibody to.