Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
4/6 inhibitor and, S1400D evaluating AZD4547, an FGFR inhibitor. The nonmatch
study S1400I tests nivolumab + ipilimumab vs. nivolumab. Two studies
have closed: S1400E evaluating rilotumumab an HGF monoclonal antibody +
erlotinib closed 11/26/2014 and S1400A evaluating MEDI4736 in non-match
pts, closed 12/18/2015. Results: From June 16, 2014 to June 15, 2016, 812 pts
were screened and 292 pts registered to a study: 116 to S1400A, 27 to S1400B,
53 to S1400C, 32 to S1400D, 9 to S1400E and 55 to S1400I. Demographics:
Screening was successful for 705 (87%) of screened eligible pts. Median age
67 (range 35-92); male 68%; ECOG PS 0-1 88%, PS 2 10%; Caucasian 85%, Black
9%, other 5%; never/former/current smokers 4%/58%/36%. Table 1 displays
biomarker prevalence; 39% of pts matched; 33.9%, 4.8%, and 0.3% with 1,
2, and all 3 biomarkers, respectively. Tumor mutation burden (TMB) was
available for 636 (90.4%) of eligible pts. The distribution of TMB is: 126 (19.8%)
low (≤5 mutations Mb), 415 (65.1%) intermediate (6-19 mutations/Mb), and
96 (15.1%) high (≥20 mutations/Mb). The median TMB was 10.1. Conclusion:
Genomic screening is feasible as part of this master protocol designed to
expedite drug registration, confirm anticipated prevalence of targeted
alterations in SCCA and reveal intermediate or high TMB in most (80.2%) pts.
Treatment results are not yet available as patients continue to accrue. Clinical
trial information: NCT02154490
Total FGFR CDK PIK3CA
FGFR
(15.9%)
12.9% 2.4% 0.6%
CDK
(18.8%)
14.6% 1.8%
PIK3CA
(8.8%)
6.4%
Biomarker
prevalence
and overlap.
Keywords: genomic screening, umbrella trial, S1400, Squamous cell lung
cancer
MA16: NOVEL STRATEGIES IN TARGETED THERAPY
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
MA16.11 CNS RESPONSE TO OSIMERTINIB IN PATIENTS WITH
T790M-POSITIVE ADVANCED NSCLC: POOLED DATA FROM TWO
PHASE II TRIALS
Glenwood Goss 1 , Chun-Ming Tsai 2 , Frances Shepherd 3 , Myung-Ju Ahn 4 ,
Lyudmila Bazhenova 5 , Lucio Crinò 6 , Filippo De Marinis 7 , Enriqueta Felip 8 ,
Alessandro Morabito 9 , Rachel Hodge 10 , Mireille Cantarini 11 , Tetsuya
Mitsudomi 12 , Pasi Jänne 13 , James Chih-Hsin Yang 14
1 Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa,
Ottawa/ON/Canada, 2 Taipei Veterans General Hospital and School of Medicine,
National Yang-Ming University, Taipei/Taiwan, 3 University Health Network,
Princess Margaret Cancer Centre, Toronto/Canada, 4 Medicine, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul/Korea, Republic
of, 5 Uc San Diego Health, Moores Cancer Center, San Diego/CA/United States of
America, 6 Santa Maria Della Misericordia Hospital, Azienda Ospedaliera Di Perugia,
Perugia/Italy, 7 Thoracic Oncology Division, European Institute of Oncology, Milan/
Italy, 8 Vall D’Hebron Institute of Oncology, Barcelona/Spain, 9 Instituto Nazionale
Tumori Di Napoli, Naples/Italy, 10 Astrazeneca, Cambridge/United Kingdom,
11 Astrazeneca, Macclesfield/United Kingdom, 12 Thoracic Surgery, Kindai University
Faculty of Medicine, Osaka-Sayama/Japan, 13 Lowe Center for Thoracic Oncology,
Dana-Farber Cancer Institute, Boston/United States of America, 14 Cancer Research
Center, National Taiwan University, Taipei/Taiwan
Background: Brain metastases develop in 25–40% of patients with NSCLC.
Osimertinib is an oral, potent, irreversible EGFR-TKI, selective for both
sensitising (EGFRm) and T790M resistance mutations. Preclinical and early
clinical evidence support central nervous system (CNS) penetration and
activity of osimertinib. Two Phase II studies (AURA extension [NCT01802632]
and AURA2 [NCT02094261]) evaluating the efficacy and safety of osimertinib
are ongoing. We present a pre planned subgroup analysis assessing pooled
CNS response from these two studies; data cut-off (DCO) was 1 November
2015. An earlier pooled analysis from these two studies (1 May 2015 DCO)
showed the objective response rate (ORR) in patients with CNS metastases
was consistent with ORR in the overall patient population. Methods: Patients
with advanced NSCLC who progressed following prior EGFR-TKI therapy
with centrally-confirmed T790M positive status (cobas® EGFR Mutation
Test) received osimertinib 80 mg once daily (n=411). Patients with stable,
asymptomatic CNS metastases were eligible for enrolment. CNS efficacy
was assessed in an evaluable for CNS response analysis set, which included
patients with at least one measurable CNS lesion on baseline brain scan
(RECIST v1.1) by blinded independent central neuroradiology review (BICR).
Effect of prior radiotherapy on CNS response was assessed. Results: As of
1 November 2015, 50/192 patients with baseline brain scans had at least
one measurable CNS lesion identified by BICR. Baseline demographics were
broadly consistent with the overall patient population. Confirmed CNS
ORR was 54% (27/50; 95% CI: 39%, 68%), with 12% complete CNS response
(6/50 patients). The median CNS duration of response (22% maturity) was
not reached (95% CI: not calculable [NC], NC). The estimated percentage of
patients remaining in response at 9 months was 75% (95% CI: 53, 88). CNS
disease control rate (DCR) was 92% (46/50; 95% CI: 81%, 98%). Median time
to first response was 5.7 weeks (range: 5.6–6.6). Median best percentage
change from baseline in CNS target lesion size was 53% (range: -100% – +80%).
Median follow up for CNS progression-free survival (PFS) was 11 months; the
median CNS PFS was not reached (95% CI: 7, NC). At 12 months, 56% (95%
CI: 40%, 70%) of patients were estimated to remain on study, alive and CNS
progression-free. CNS response was observed regardless of prior radiotherapy
to the brain. Conclusion: Osimertinib demonstrates durable efficacy in
patients with T790M NSCLC and measurable CNS metastases, with a CNS
response rate of 54% and a DCR of 92%.
Keywords: brain metastases, AZD9291, osimertinib, T790M
SESSION MA17: GENETIC DRIVERS
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
MA17.01 MICROARRAY IDENTIFICATION OF GENETIC DRIVERS OF
BRAIN METASTASIS IN LUNG ADENOCARCINOMA
Gavitt Woodard 1 , Vivianne Ding 1 , Matthew Rosenblum 1 , Fleur Leguay 1 , Clara
Zoon-Besselink 1 , Kirk Jones 2 , Tasha Lea 3 , Michael Mcdermott 4 , Il-Jin Kim 1 ,
David Jablons 1
1 Surgery, University of California, San Francisco, San Francisco/CA/United States
of America, 2 Pathology, University of California, San Francisco, San Francisco/
United States of America, 3 Pathology, University of California, San Francisco, San
Francisco/CA/United States of America, 4 Neurosurgery, University of California,
San Francisco, San Francisco/United States of America
Background: Brain metastasis in non-small cell lung cancer (NSCLC) develop
in 20-40% of all patients and represent a major cause of NSCLC morbidity and
mortality. The mechanisms driving metastatic potential across the bloodbrain-barrier
remain poorly understood. Methods: Affymetrix microarray
was performed on RNA extracted from 75 pairs of snap-frozen primary lung
adenocarcinoma and matched normal lung tissue. Changes in gene expression
from the primary lung adenocarcinomas that did not ever metastasize to brain
over up to 15 years of follow up were compared to the lung adenocarcinomas
that ultimately seeded a brain metastasis. From these 75 patients, tissue
from 5 paired snap-frozen brain metastases was also available and gene
expression changes between the primary lung adenocarcinomas and matched
brain metastases were investigated to identify genes and pathways of
interest in the development of brain metastasis. Affymetrix Transcriptome
Analysis Console software was used for data analysis and interpretation
with fold changes >2.0 and p-value of