PO-077: Cetuximab Plus Radiotherapy for Chinese Patients with Locally Advanced Head and Neck Cancer

S32 EXTREME regimen were evaluated in a cohort of unselected patients outside clinical trial. Materials and Methods: 22 patients with recurrent and/or metastatic HNSCC were treated with 5-FU, cisplatin and cetuximab from October 2009 to Marts 2012. Biopsies from all patients histologically tested for HPV-status by p16 immunostaining. The patients received a maximum of six cycles of 5-FU (1000 mg/m2 per day for 4 days), cisplatin (100 mg/m2), and cetuximab (400 mg/m2, as a loading dose, followed by 250 mg/m2 per week), followed by cetuximab maintenance with 250mg/m2 every week until disease progression, unacceptable toxicity or death. Endpoints were overall response rate (ORR), disease control rate (DCR) (= complete and partial response or stable disease), progression-free survival (PFS), overall survival (OS), and the toxicity of the treatment. One patient received two cycles of the treatment as induction prior to brachytherapy and is therefore only included in the toxicity evaluation and not in ORR, DCR, PFS or OS. Results: In the analysed population of 21 patients ORR was 29 % (0 CR, 6 PR) and DCR was 48% (0 CR, 6 PR, 4 SD). Median PFS was 5.8 months (95 % confidence interval (CI) 4.3 – 7.3) and median OS was 7.3 months (95 % CI 5.0 – 9.7). Among adverse events grade 3 or 4 were hypokalemia (46 %), neutropenia (36 %), febrile neutropenia (23 %), thrombosis (23 %), and anaphylactic reaction (9 %). Two patients died of febrile neutropenia after one cycle of treatment. None of two deaths were considered to be related to cetuximab. 11 patients were HPV-negative and 9 patients were HPVpositive. The HPV-positive patients had a better survival than the HPV-negative. Conclusions: This study indicates that the combination of 5FU, cisplatin and cetuximab in patients with recurrent and/or metastatic HNSCC may be more toxic when used in an unselected population than the results published from the EXTREME trial. Two patients died from direct side effects from treatment, and 23% had grade 3 thrombosis complications. Regimens of cetuximab and chemotherapy with less toxicity for the palliative treatment of these patients should be investigated.

4th ICHNO Results: One patient died of anaphylactic shock, two discontinued study-participation on their own request. One patient died immediately after end of Re-RT, one was lost to follow–up. Median follow-up time for patients alive is 18.2 months (range: 11-35). Thus, 20 patients were evaluable for toxicity while 18 patients received follow-up imaging with MRI, CT or PET/CT scans and were completely evaluable for treatment response. Grade 3 side effects are documented for dermatitis (35%), dysphagia (30%), acneiform rash (23.8%), mucositis (15%), voice change (15%) and pain (9.5%). 4 patients attained a complete response (CR), 3 a partial response (PR), 2 stable disease (SD) and 9 progressive disease (PD). The median overall survival time is 12.2 months; the 1year OS rate 30.4%. Multivariate analysis does not demonstrate any influence of acne form rash, PET based planning or number of unresectable recurrences on survival. All patients with SCC histology progressed; 2 are still alive. One patient with recurrent high grade MEC is in complete response and still alive 42 months after finishing treatment. Conclusions: Re-RT with concurrent cetuximab is feasible at acceptable toxicity for previously irradiated patients with HNC. Given a comparable survival for patients reirradiated only or for patients administered systemic treatment (cisplatin, 5-FU, cetuximab) we suggest to sequentially treat relapsed HNC with single modalities.

PO-076 COMBINED REIRRADIATION AND CETUXIMAB FOR LOCALLY RECURRENT HEAD AND NECK CANCER Ñ MATURE OVERAL SURVIVAL RESULTS D. Milanovic1, A.L. Grosu1, G. Rücker2, M. Henke1 1 Universitätsklinik Freiburg, Department of Radiation Oncology, Freiburg, Germany 2 Universitätsklinik Freiburg, Institute of Medical Biometry and Medical Informatics, Freiburg, Germany

PO-077 CETUXIMAB PLUS RADIOTHERAPY FOR CHINESE PATIENTS WITH LOCALLY ADVANCED HEAD AND NECK CANCER L. Gao1, J. Pan2, S. Wu3, C. Xie4, M. Zhong5, X. Chen6, Y. Jin7, G. Wu8, J. Cai9, G. Xu1 1 Chinese Academy of Medical Science, Cancer Institute and Hospital, Beijing, China 2 Fujian Tumor Hospital, Radiation Oncology Department, Fuzhou, China 3 Sun Yat-sen University Cancer Center, Radiation Oncology Department, Guangzhou, China 4 Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei, China 5 Xiangya Hospital of Central South University, Department of Oncology, Hunan, China 6 Zhejiang Cancer Hospital, Radiation Oncology Department, Zhejiang, China 7 Ruijin Hospital, Radiotherapy and Chemotherapy Department, Shanghai, China 8 Huazhong University of Science and Technology, Cancer Centre Union Hospital of Tongji Medical College, Hubei, China 9 Merck Serono (Beijing) Pharmaceutical R&D Co. Ltd, Global Clinical Development Center Oncology, Shanghai, China

Purpose/Objective: Patients with recurrent, unresectableand previously irradiated head and neck cancer (HNC) may expect 5-year survival rates of approximately 15% following reirradiation (Re-RT). Chemotherapy with or without epidermal growth factor receptor (EGFR) inhibition is established as efficient palliative management. This phase I/II retrospective monocentric study investigates feasibility, toxicity and outcome of Re-RT combined with EGFR blockade for these patients. Materials and Methods: Between June 2008 and June 2011, we reirradiated (50.4-66.6 Gy, 5X 1.8 Gy/Week) 23 patients (20 male and 3 female) with histologically proven locally recurrent unresectable HNC, who had been previously treated with external beam radiotherapy. 22 patients had a squamous cell carcinoma (SCC), one patient high grade mucoepidermoid carcinoma (MEC). RT-planning was based to FDG-PET findings in 14 patients and on CT or MRI findings in the remaining. Concommittant EGFR blockade with Cetuximab was given initially at 400 mg/m2 two days before Re-RT and weekly (250 mg/m2) thereafter. Patients were seen weekly during the radiation course and at 3 months intervals in follow-up thereafter.

Purpose/Objective: The addition of cetuximab to radiotherapy (RT) significantly improved locoregional control, survival and progression-free survival (PFS) compared with RT alone in a phase III trial in Western patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) (Bonner et al, NEJM 2006). This trial investigated the safety and anti-tumor activity of cetuximab+RT in a similar population of Chinese patients with LASCCHN. Materials and Methods: This was an open-label, single-arm, multicenter trial. Chinese patients with previously untreated stage III/IV non-metastatic SCC of the oropharynx, hypopharynx or larynx received cetuximab from weeks -1 to 6 (400 mg/m2 initial infusion then 250 mg/m2/week) with concomitant boost RT from weeks 1 to 6 (total dose of 72.0 Gy in 42 fractions).The primary endpoint was best overall response assessed by the investigator according to modified WHO criteria. Results: From February 2009 to April 2010, 70 patients were screened and 66 were treated (intention-to-treat [ITT] population). Demographics and disease characteristics at baseline were: male (89.4%); median age 55.0 years (range 49.0–63.0 years); Karnofsky performance status ≥90% (68.2%),

4th ICHNO 80% (31.8%); stage IV (Union for International Cancer Control v. 6, 2002) disease (81.8%); and hypopharynx as the main primary tumor site (50.0%). Two patients withdrew after the first dose of cetuximab (infusion-related reaction, n=1; preexisting esophageal cancer, n=1). The overall response rate was 68.2% (45/66) (95% CI 55.6–79.1), with 28 (42.4%) complete responses. The median PFS was 9.4 months (95% CI 7.7–11.2). Overall survival data are not yet mature. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 39.4% of patients and included mucosal inflammation (22.7%) and radiation skin injury (4.5%). Grade 3/4 special AEs included skin reactions (3.0%) and infusionrelated reactions (3.0%). Cetuximab-related TEAEs were reported in 84.8% of patients and serious TEAEs in 7.6% of patients. Two TEAEs leading to death were reported; neither was related to cetuximab. Conclusions: Cetuximab+RT demonstrated promising antitumor activity in Chinese patients, with no new or unexpected safety findings. PO-078 CETUXIMAB PLUS CHEMOTHERAPY FOR ASIAN PATIENTS WITH RECURRENT AND/OR METASTATIC HEAD AND NECK CANCER Y. Guo1, M. Shi2, A. Yang3, C. Hu4, R. Luo5, Y. Zhang6, L. Zhou7, Y. Cheng8, T. Li9, Y. Shi10 1 Fudan University Shanghai Cancer Center, Medical Oncology Department, Shanghai, China 2 The First Affiliated Hospital of the Fourth Military Medical University, Xijing Hospital, Xi'an, China 3 Sun Yat-sen University Cancer Center, Head & Neck Department, Guangzhou, China 4 The Second Xiangya Hospital of Central South University, Oncology Department, Changsha, China 5 Nanfang Hospital, Cancer Medical Department, Guangzhou, China 6 Hangzhou Zhejiang Cancer Hospital, Chemotherapy Center, Hangzhou, China 7 Eye and ENT Hospital of Fudan University, Head and Neck Surgery Department, Shanghai, China 8 Jilin Cancer Hospital, Surgical Department, Jilin, China 9 Merck Serono (Beijing) Pharmaceutical R&D Co. Ltd, Global Clinical Development Center, Shanghai, China 10 Chinese Academy of Medical Sciences, Medical Oncology Department Cancer Institute & Hospital, Shanghai, China Purpose/Objective: The addition of cetuximab to cisplatin (P) and 5-fluorouracil (F) significantly improved survival (OS), progression-free survival (PFS) and overall response rate (ORR) vs PF alone in Western patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in the phase III EXTREME trial (Vermorken et al, NEJM 2008).The present trial investigated first-line PF+cetuximab in Asian pts with R/M SCCHN. Materials and Methods: In this open-label, single-arm, multicenter study, Asian pts with confirmed R/M SCCHN and with no prior systemic therapy (except as part of a multimodality therapy) received cetuximab (400 mg/m2 initial infusion then 250 mg/m2/week) and up to six 3-weekly cycles of P (75 mg/m2, day 1) and F (750 mg/m2/day, 24-hour infusion, days 1–5). The primary endpoint was best overall response assessed by the investigator according to modified WHO criteria. Results : Between December 2009 and September 2010, 73 pts were enrolled from 14 sites in China and South Korea and 68 were treated. Patient and disease characteristics were: 92.6% Chinese; 72.1% male; median age 55.5 years; main primary tumor sites oral cavity (38.2%) and larynx (23.5%); and 92.6% stage IV disease. The ORR of 54.4% (37/68: 2 complete and 35 partial responses) (Table) was in line with that reported for PF+cetuximab in the EXTREME trial (36%). The median PFS time of 6.2 months was also similar to that for PF+cetuximab in the EXTREME trial (5.6 months). OS data are not yet mature. Grade 3/4 adverse events were seen less

S33 frequently than in the EXTREME trial (58.8% vs 82%), the most common being neutropenia (16.2%), hypokalemia (10.3%), leucopenia (8.8%) and hypomagnesemia (7.4%). Grade 3 skin reactions were seen in one pt and grade 3 infusion-related reactions in two pts. Table. Efficacy: intention-to-treat population Parameter (n=68) Overall response rate (WHO), % 54.4 95% CI 41.9–66.5 Duration of response, months 5.7 95% CI 4.2–9.1 Median progression-free survival, months 6.2 95% CI 5.1–8.1 50.1 6-month progression-free survival rate, % (22 pts at risk) 36.4–63.9 95% CI Median time to progression, months 6.8 95% CI 5.3–8.1 6-month overall survival rate, % 80.1 (34 pts at risk) 95% CI 69.9–90.3 CI=confidence intervals. Conclusions: In Asian pts with R/M SCCHN, PF+cetuximab demonstrated antitumor activity and safety in line with that observed in Western pts. PO-079 REVIEW OF CETUXIMAB VERSUS CISPLATIN CONCURRENT WITH RADIOTHERAPY IN LAHNSCC: A SINGLE INSTITUTION EXPERIENCE D. Cagney1, L. Walsh1, M. Dunne1, C. Gillham1, I. Fraser1, D. Hollywood1, J. Armstrong1, P. Thirion1, S. Brennan1 1 St Luke's Hospital, Department of Radiation Oncology, Dublin, Ireland Republic of Purpose/Objective: There is a lack of consensus regarding the role of cetuximab in the management of locally advanced head and neck cancer (LAHNC). There is a concern that the low toxicity rates reported in the clinical trial setting may not translate into the community setting. We previously reported an increased rate of acute mucositis with concurrent cetuximab radiotherapy (CTX/RT) compared to cisplatin radiotherapy (CDDP/RT). We now report late toxicity rates and survival outcomes for concurrent cetuximab compared to cisplatin radiotherapy in LAHNC. Materials and Methods: A single institution retrospective review of all patients treated with radical RT and concomitant CTX, as per the Bonner protocol. Between January 2006 and June 2007, 34 patients with LAHNC were treated with concomitant CTX and RT. To allow for comparison a historical matched control group receiving concurrent CDDP and RT, consisting of 33 patients treated between October 2004 and August 2007 was identified from the institutional database. Results: Median age of patients receiving CTX was 63 years as opposed to those receiving CDDP who were 59 years (p=0.253). Performance status between groups was equivalent with majority of patients WHO PS 0 (CTX-95%, CDDP-97%). There was a higher proportion of AJCC Stage 4 patients in the CTX group (65%) in comparison to the CDDP group (55%) (p=0.549). A higher proportion of patients receiving CTX experienced PEG dependence more than 6 months following completion of treatment (26% v 12%, p=0.24), grade 3+ skin dermatitis (9% v 3%, p=0.628) and oesophageal toxicity (9% v 3%, p=0.628), than those on CDDP. After a median follow-up of 22.6 months the median overall survival from the end of RT was 14.1 months (95% CI: 0 – 28.2) for the CTX group and 26.4 months (95% CI: 0.1 – 52.8) for the CDDP group (p=0.216). Four year survival was 32% for CXT/RT and 42% for CTX/RT group (95% CI: -0.13 – 0.33). The