6th ICHNO Abstract Book

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page 14 6th ICHNO
6 th ICHNO Conference
International Conference on innovative approaches in Head and Neck Oncology
16 – 18 March 2017
Barcelona, Spain
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OC-021 Biomarker results from BERIL-1: buparlisib and
paclitaxel in patients with platinum-pretreated SCCHN
D. Soulières1, S. Faivre2 , R. Mesía3, E. Remenár4, S.H. Li5,
A. Karpenko6, A. Dechaphunkul7, U. Keilholz8, L. Kiss9, J.C.
Lin 10, R. Nagarkar11, L. Tamás12, S.B. Kim13, J. Erfán14, A.
Alyasova15, A. Yovine16, S. Le Mouhaër17, N. Solovieff18 , S.
Turri17, L. Licitra19
1Centre Hospitalier de l'Université de Montréal, Oncology
Department, Montréal, Canada
2Hôpitaux Universitaires Paris Nord Val de Seine HUPNVS,
Oncology Department, Paris, France
3Institut Català d’Oncologia ICO L’Hospitalet- University
of Barcelona, Medical Oncology Department, Barcelona,
Spain
4Országos Onkológiai Intézet, Head and Neck
Department, Budapest, Hungary
5Kaohsiung Chang Gung Memorial Hospital, Department
of Internal Medicine, Kaohsiung Hsien, Taiwan
6Leningrad Regional Oncology Dispensary, Oncology
Department, Saint Petersburg, Russian Federation
7Prince of Songkla University, Department of Internal
Medicine, Songkhla, Thailand
8Charité Comprehensive Cancer Center, Oncology
Department, Berlin, Germany
9Szent Imre University Teaching Hospital, Oncology
Department, Budapest, Hungary
10Taichung Veterans General Hospital, Department of
Radiation Oncology, Taichung, Taiwan
11Curie Manavata Cancer Center, Oncology Department,
Maharashtra, India
12Semmelweis University, Department of
Otorhinolaryngology- Head and Neck Surgery, Budapest,
Hungary
13Asan Medical Center- University of Ulsan College of
Medicine, Oncology Department, Seoul, Korea Republic
of
14Jósa András Teaching Hospital, Oncology Department,
Nyíregyháza, Hungary
15Federal Budget Medical Institution, Oncology
Department, Nizhny Novgorod, Russian Federation
16Novartis Pharma AG, Novartis Pharmaceuticals, Basel,
Switzerland
17Novartis Pharma S.A.S., Novartis Pharmaceuticals,
Paris, France
18Novartis Institutes for BioMedical Research, Novartis
Pharmaceuticals, Cambridge, USA
19Fondazione 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
predictive biomarkers.
Material and Methods
In total, 158 patients received buparlisib (100 mg/day) +
paclitaxel (80 mg/m2/week) or placebo + paclitaxel (n=79
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.