Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
option in these patients. Furthermore ROS1 rearrangements are found
in approximately 1-2% with various rearrangement partners. First clinical
trials confirmed it´s pivotal role in NSCLC tumorigenesis as pharmacologic
inhibition leads to tumor regression and durable response rates. We present
a case report of a 74year old, ECOG 1 female patient, formerly smoker
(15py), presenting with a relapsed, formerly stage II classified, metastatic
L858R EGFR mutated adenocarcinoma, that progressed after 11months on
Erlotinib therapy and harbored a T790M mutation as well as a bypassing
ROS1 translocation. We initiated Osimertinib therapy and performed
a short term radiologic evaluation after 4 weeks on the 3rd generation
TKI. Methods: Tumor biopsies were obtained after clinical and radiologic
findings of progressive disease and were analyzed by FISH for ROS1 and
ALK (split fish technique), cMET (FISH) and EGFR (Therascreen EGFR-test
by Qiagen). PET CT scans were performed before initiation of and 4 weeks
after continuous Osimertinib therapy. Results: Molecular analysis revealed
a T790M gatekeeping mutation, in addition a ROS1 (45% of vital tumor cells)
translocation was detected. PET CT scans after Erlotinib failure confirmed
metastatic and progressive disease with hypermetabolic and enlarged lymph
nodes in the mediastinum and widespread tumor lesions juxtaposed to the
pleural cavity at the right hemithorax with infiltration of the osseus thoracic
wall. 4 weeks after initiation of Osimertinib therapy, repeated PET CT scans
showed a partial remission of tumor burden with a concomitant complete
resolution of pathologic glucose uptake. Conclusion: This is a rare case
describing a tumor progress after acquired EGFR TKI resistance harboring a
T790M mutation in addition to a ROS1 rearrangement. After one month of
treatment with Osimertinib we found a metabolic CR indicating that ROS1
rearrangement had no clinical significance in this situation.
Keywords: ros1, osimertinib, NSCLC, T790M
Yoo-Duk Choi, Tae-Ok Kim, Hyeong-Won Seo, Sung Ahn, Jin-Sun Jang, Cheol-
Kyu Park, Young-Chul Kim, Ju-Sik Yun, Sang-Yun Song, Kook-Joo Na, Mee-Sun
Yoon, Sung-Ja Ahn, Hyun-Ju Seon, Seong Young Kwon, In-Jae Oh
Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital,
Jeonnam/Korea, Republic of
Background: After failure of epidermal growth factor receptor-tyrosine kinase
inhibitor (EGFR-TKI), re-biopsy may be helpful to understand resistance
mechanism and guide further treatment decision. However, re-biopsy is still
challenging due to several hurdles, such as tissue availability, procedural
feasibility, and limited new drugs. The aim of this study was to assess the
feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC)
in a real-practice. Methods: We retrospectively reviewed the clinical and
pathologic data of advanced NSCLC patients who had disease progression
after previous EGFR-TKI at single institution between January 2015 and
February 2016. Results: Ninety-one patients had disease progression after
using EGFR-TKI. Among them, thirty-three patients (36.3%) underwent
re-biopsy. re-biopsy was successfully completed for thirty-two patients
(97.0%) and only one patient didn’t get malignant cell. Three patients (9.1%)
experienced a pneumothorax, however only one patient required closed
thoracostomy. After re-biopsy, 27 patients were performed EGFR mutation
test. Among 21 patients who had active mutation, the initial mutation was
again found in 9 cases (42.9%) while the T790M mutation was found in 6
cases (28.6%). In 4 cases the initial EGFR mutation was no longer found. The
patients who had re-biopsy were younger (61.2±9.7 vs. 66.1±10.8 years, p=0.03)
and longer response duration (429±383 vs. 265±284 days, p=0.022) than the
patients who didn’t. Conclusion: Re-biopsy in advanced NSCLC is feasible
in the real practice especially in younger patient and patients with longer
response duration of EGFR-TKI.
Keywords: re-biopsy, EGFR mutation, T790M
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-111 CAN WE AVOID USING CHEMOTHERAPY IN MANAGING
ACQUIRED RESISTANCE OF EGFR-MUTATED NSCLC?
Thongbliew Prempree
Oncology and Gene Therapy, Chularat3 Hospital, Samutprakarn/Thailand
Background: Since the discovery of Non small cell lung cancer with activating
mutation of EGFR, most studies have proved that EGFR tyrosine kinase
inhibitor to be the treatment of choice with high degree of success and
with median response duration of one year. Acquired resistance of EGFR
- TKI is inevitable due to various mechanisms including T790M mutation
of EGFR, exon 20 . Managing acquired resistance of EGFR mutated NSCLC
requires special consideration to obtain success particularly to avoid using
chemotherapy. Methods: From our own series of advanced NSCLC ,42 patients
were indentified as having EGFR mutation for which TKI was used along with
other targeted medicine such as Bevacizumab. Of 42 patients treated with
multitargeted medicines, 21 cases had proven T790M mutatiom from rebiopsy
while the rest may have T790M or other activating mutations without
proven. Those who developed resistance to TKI must have tumor markers
rising and tumor site progression and finally have muliple organs progression.
Treatment of resisitance included: 1.) Change to second generation of TKI
such as Afatinib 2.) Use Anti-PI3K or mTOR-inhibitor such as Torisel 20 mg IV
weekly Results: 21 cases of T790M activating mutation came from: 1.) 22 cases
of classical exon 19 deletion had 5 cases of T790M 2.) 7 cases of exon 21 point
mutation had 6 cases of T790M 3.) 13 cases of various exon 19 mutation had
10 cases of T790M All 21 cases of T790M servived the resistance treatment
at least 1 year after the discovery T790M. Conclusion: Our results appeared
to show; 1.) Multiple targeted medicines treatment appreared to reduce the
resistance to TKI 2.) Those harbored classical exon 19 deletion appreared to
have less TKI resisitance 3.) Those harbored exon 21 EGFR mutation and nonclassical
exon 19 mutation appreared to have TKI resistance more (average
1 year) 4).We could avoid using chemotherapy in those who developed TKI
resistance at least in a short period of time and it will require further study
Keywords: EGFR-TKI resistance
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-112 FEASIBILITY OF RE-BIOPSY IN PATIENTS WITH NON-
SMALL CELL LUNG CANCER AFTER FAILURE OF EPIDERMAL
GROWTH FACTOR RECEPTOR TARGETED THERAPY
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-113 CLINICAL COURSE OF NSCLC PATIENTS WITH EGFR
MUTATION UNDERGOING REBIOPSY AND OSIMERTINIB THERAPY
Kenichiro Hirai 1 , Hiroshi Yokouchi 2 , Tatsuhiko Koizumi 1 , Hiroyuki Minemura 1 ,
Kana Watanabe 3 , Tatsuro Fukuhara 3 , Kenya Kanazawa 1 , Makoto Maemondo 3 ,
Yoshinori Tanino 1 , Mitsuru Munakata 1
1 Department of Pulmonary Medicine, Fukushima Medical University, Fukushima/
Japan, 2 Fukushima Medical University, Fukushima/Japan, 3 Respiratory Medicine,
Miyagi Cancer Center, Natori/Japan
Background: Osimertinib, a third-generation epidermal growth factor
receptor (EGFR)-tyrosine kinase inhibitor (TKI), was approved in May 2016
in Japan. Its administration requires a tumor rebiopsy to detect the EGFR
T790M mutation. AURA and AURA2 studies with 411 patients demonstrated
a remarkable clinical outcome with an overall response rate (ORR) of around
65% and progression-free survival (PFS) of 9.7 months. Several authors
reported that the detection rate of T790M by tumor rebiopsy in these
patients was approximately 52 to 68%. However, thorough accumulation of
data is required to establish the clinical relevance of T790M detection and
osimertinib response. Methods: We retrospectively reviewed the clinical
courses of NSCLC patients with the EGFR mutation, who had undergone
rebiopsies and osimertinib therapy. Results: Eleven patients with the EGFR
mutation (exon19del [n=10] and L858R [n=1]) were included. Average age was
67 years old (range 53–79). The following EGFR-TKIs were administered to
the 11 patients before rebiopsy; elrotinib (n=6), afatinib (n=5) and gefitinib
(n=2). The patients received rebiopsy in the 2nd line treatment (n=3), 3rd
line (n=2), 5th line (n=2), 6th line (n=2) and 7th line (n=2). Rebiopsy sites
were primary lung tumors (n=8), supraclavicular lymph node (n=1), liver
metastasis (n=1) and pleural effusion (1). Among them, T790M was detected
in four, zero, one, and one, respectively (detection rate: 54.5%). Rebiopsy was
successfully performed in all patients, among whom one required a second
attempt. ASP8273, another third-generation EGFR-TKI, and osimertinib
were administered in one and two patients, respectively. The remaining two
patients are to be treated with osimertinib. Both patients who received
osimertinib achieved partial response, and their ECOG performance status
(PS) was remarkably improved from 4 to 1, and 3 to 1. One of the two patients
experienced grade 4 neutropenia; thus, the osimertinib dose was reduced
from 80 mg to 40 mg daily. The remaining patient suffered from erythema;
however, it was improved after ten-day cessation of medication. Osimertinib
was then resumed at 80 mg daily with no severe side effects experienced
thereafter. Conclusion: The detection rate of T790M by rebiopsy was
consistent with previous reports. Osimertinib was feasible and effective for
our patients with poor PS; however, a prospective study is required to confirm
osimertinib’s validity for such patients. In WCLC 2016, we will increase the
number of patients who undergo rebiopsy and osimertinib therapy, and we
S662 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017