6th ICHNO Abstract Book

page 14 6 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 16 – 18 March 2017 Barcelona, Spain __________________________________________________________________________________________ 6th ICHNO

OC-021 Biomarker results from BERIL-1: buparlisib and paclitaxel in patients with platinum-pretreated SCCHN D. Soulières 1 , S. Faivre 2 , R. Mesía 3 , E. Remenár 4 , S.H. Li 5 , A. Karpenko 6 , A. Dechaphunkul 7 , U. Keilholz 8 , L. Kiss 9 , J.C. Lin 10 , R. Nagarkar 11 , L. Tamás 12 , S.B. Kim 13 , J. Erfán 14 , A. Alyasova 15 , A. Yovine 16 , S. Le Mouhaër 17 , N. Solovieff 18 , S. Turri 17 , L. Licitra 19 1 Centre Hospitalier de l'Université de Montréal, Oncology Department, Montréal, Canada 2 Hôpitaux Universitaires Paris Nord Val de Seine HUPNVS, Oncology Department, Paris, France 3 Institut Català d’Oncologia ICO L’Hospitalet- University of Barcelona, Medical Oncology Department, Barcelona, Spain 4 Országos Onkológiai Intézet, Head and Neck Department, Budapest, Hungary 5 Kaohsiung Chang Gung Memorial Hospital, Department of Internal Medicine, Kaohsiung Hsien, Taiwan 6 Leningrad Regional Oncology Dispensary, Oncology Department, Saint Petersburg, Russian Federation 7 Prince of Songkla University, Department of Internal Medicine, Songkhla, Thailand 8 Charité Comprehensive Cancer Center, Oncology Department, Berlin, Germany 9 Szent Imre University Teaching Hospital, Oncology Department, Budapest, Hungary 10 Taichung Veterans General Hospital, Department of Radiation Oncology, Taichung, Taiwan 11 Curie Manavata Cancer Center, Oncology Department, Maharashtra, India 12 Semmelweis University, Department of Otorhinolaryngology- Head and Neck Surgery, Budapest, Hungary 13 Asan Medical Center- University of Ulsan College of Medicine, Oncology Department, Seoul, Korea Republic of 14 Jósa András Teaching Hospital, Oncology Department, Nyíregyháza, Hungary 15 Federal Budget Medical Institution, Oncology Department, Nizhny Novgorod, Russian Federation 16 Novartis Pharma AG, Novartis Pharmaceuticals, Basel, Switzerland 17 Novartis Pharma S.A.S., Novartis Pharmaceuticals, Paris, France 18 Novartis Institutes for BioMedical Research, Novartis Pharmaceuticals, Cambridge, USA 19 Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Head and Neck Cancer, Milan, Italy Purpose or Objective BERIL-1 (NCT01852292) is a Phase 2, randomized, placebo- controlled study of the pan-phosphatidylinositol 3-kinase (PI3K) inhibitor buparlisib (BKM120) and paclitaxel in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who progressed on a prior platinum-based chemotherapy regimen. At the primary analysis date (cut-off Aug 31, 2015), the study met its primary endpoint, demonstrating improved median progression-free survival (PFS) with buparlisib + paclitaxel (buparlisib arm) vs placebo + paclitaxel (placebo arm) in the full population (4.6 vs 3.5 months; hazard ratio [HR] 0.65 [95% confidence interval (CI): 0.45–0.95]). Overall response rate (ORR: complete or partial response; locally assessed) was 39% vs 14% (buparlisib vs placebo arm). At the time of overall survival (OS) analysis (cut-off Mar 30, 2016), median OS was 10.4 vs 6.5 months (HR 0.72 [95% CI: 0.49–1.04]; buparlisib vs placebo arm). Here, we report the results of exploratory analyses conducted to identify

in each arm). Genomic DNA from 84 archival tissue samples and circulating tumor DNA (ctDNA) from 112 plasma samples collected at baseline were analyzed by next-generation sequencing evaluating panels of 44 and 542 cancer-related genes (including TP53 ), respectively. The 542-gene panel used for ctDNA analysis included human papillomavirus (HPV) probes; HPV status was also assessed in 143 archival tissue samples by immunohistochemistry or fluorescence in situ hybridization. Mutational load was defined as the number of non-synonymous alterations detected in ctDNA samples for each patient. The correlation between OS and ORR with HPV and TP53 status was assessed in archival and ctDNA samples. Results HPV-negative status and TP53 alterations in archival tissue and ctDNA were associated with trends for improved OS and ORR (locally assessed by investigators) in the buparlisib arm compared to the placebo arm (Table). HPV- negative status TP53 alteration s Archival tissue (n=115/143 ) ctDNA (n=89/112 ) Archival tissue (n=52/84) ctDNA (n=43/112 ) Median OS, months (buparlisi b vs placebo arm) 10.1 vs 5.9 11.6 vs 6.5 10.9 vs 5.9 10.1 vs 5.8 HR for OS (95% CI) 0.61 (0.40– 0.92) 0.51 (0.31– 0.84) 0.52 (0.28– 0.99) 0.55 (0.27– 1.12) ORR (buparlisi b vs placebo arm) 40% vs 11% 44% vs 19% 39% vs 8% 33% vs 8% In addition, 86/112 (77%) patients with a low mutational load in ctDNA (<13 variants; based on the 75 th percentile of patients), showed a trend for improved median OS of 12.6 vs 6.5 months (HR 0.57 [95% CI: 0.34–0.97]; buparlisib vs placebo arm) and ORRs of 44% vs 19%, respectively. Conclusion Addition of buparlisib to paclitaxel is an effective treatment option for platinum-pretreated patients with recurrent/metastatic SCCHN, and may be particularly beneficial in patients with TP53 -altered, HPV-negative tumors, or those with low mutational load. Further studies are warranted to confirm the observed benefit.

predictive biomarkers. Material and Methods

In total, 158 patients received buparlisib (100 mg/day) + paclitaxel (80 mg/m 2 /week) or placebo + paclitaxel (n=79