Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
(Whole Brain Radiotherapy (WBRT) or surgery or Stereotactic Radiosurgery
(SRS) were examined. OS were compared to the expected OS according
to the lung specific GPA score as described by Sperduto. Results: Ninetyeight
patients (91%) had EGFR activating mutations, whereas 10 (9%) were
undetermined. 69% of them were nonsmokers. 77/108 patients (71.3%)
were woman. 53/108 patients (49%) had BM: 30 patients had synchronous
BM whereas 23 patients had metachronous BM. 20/53 patients (38%) were
treated with WBRT. BM is still a burden for NSCLC patients harbouring EGFR
activating mutations, (median OS 42 vs 25.5 months, p = 0.0052). OS from
BM diagnosis was significantly superior in patients with EGFR activating
mutations, compared to the expected OS in accordance with Sperduto’s
GPA score (1): group 0-1 (11.5 months IC 95% [8.5-25.7] vs 3.02 months IC 95%
[2.63-3.84]); group 1.5-2 (28 months IC 95% [24.3-NR] vs 5.49 months IC 95%
[4.83-6.40]) (p = 0.026). Among EGFR activating mutations, OS were also
significantly longer in group 1.5-2 than in group 0-1 (28 vs 11.5 months) (p =
0.026) Conclusion: Currently, Lung specific GPA is not accurate enough to
estimate survival time for EGFR mutant patients. However, this tool is still
reliable to distinguish different prognosis for patient with EGFR activating
mutations, according to their GPA score. In conclusion, EGFR status modifies
OS of patients and should be integrated in the items of the GPA score. These
results should be validated in further prospective studies.
Keywords: GPA score, brain metastases, EGFR mutation
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-014 MONITORING OF T790M MUTATION IN SERUM FOR
PREDICTION OF RESPONSE TO THIRD GENERATION INHIBITORS
Teresa Morán 1 , Enric Carcereny 2 , Joaquim Bosch-Barrera 3 , Carles Mesia 4 ,
Remedios Blanco 5 , Yolanda Garcia 6 , Diana Roa 3 , Elia Sais 3 , Eudald Felip 1 ,
Cristina Queralt 7 , Itziar De Aguirre 7 , Jose Luis Ramirez 7 , Olga Fernandez 1 ,
Rafael Rosell 7
1 Medical Oncology, Catalan Institute of Oncology-Hospital Germans Trias I Pujol,
Badalona/Spain, 2 Medical Oncology, Catalan Institute of Oncology-Hospital
Germans Trias I Pujol, Barcelona/Spain, 3 Medical Oncology, Ico-Girona, Girona/
Spain, 4 Medica Oncology, Ico- Duran I Reynalds, L’Hospitalet de Llobregat,
Barcelona/Spain, 5 Medical Oncology, Consorci Sanitari de Terrassa - Hospital de
Terrassa, Terrassa, Barcelona/Spain, 6 Medical Oncology, Corporació Sanitària
Parc Taulí, Sabadell, Barcelona/Spain, 7 Molecular Biology Laboratory of Cancer
Dr. Rosell., Can Ruti Campus: Institute for Predictive and Personalized Medicine of
Cancer (IMPPC)- Institut of Health Germans Trias I Pujol (IGTP). Catalan Institute of
Oncology (ICO), Badalona, Barcelona/Spain
Background: The emergence of T790M mutation (T790M) represents the
main mechanism of acquired resistance (AR) to 1 st and 2 nd generation tyrosine
kinase inhibitors (TKIs) in EGFR mutant patients (p). Recently, 3rd generation
inhibitors (T790Mi) have demonstrated activity in EGFR mutant (mu) patients
with AR to TKIs harboring T790M. Serum and plasma have been used as an
alternative to tissue to detect both sensitizing EGFRmu and T790M. We
evaluated if (1) T790M could be monitored along T790Mi therapy in p with
baseline T790M in serum, (2) T790M loss could be correlated to clinical and
radiographic response, and (3) T790M disappears soon in rapid responders.
Methods: 10 p out of a total of 15 T790M+p treated with T790Mi were selected
according the baseline T790M+ in serum. Baseline characteristics, data on
changes in T790M in serum; and radiographic and symptom changes along
T790Mi therapy were collected. T790M in serum was detected using a PNAlocked
nucleic PCR clamp-based technique. T790M was evaluated at baseline
and at certain times after T790Mi initiation. Results: 80% of the p were
female and never smoker; 100% were adenocarcinoma, Caucasian, del19, and
were treated with previous TKI, with a median (m) time to treatment failure
of 11.25 months (mo) [range (r)1-19 mo]. P received 2 previous treatments
(r1-6), 40% had a rebiopsy for T790M evaluation, had 3 metastatic sites (r1-6),
and had a PS 1 in 70% of the cases. 5 p were evaluable for response with 2 SD
and 3 PR as best response (BR) in the 1 st evaluation. 7 out of 9 p evaluable for
clinical response, experienced an improvement in baseline symptoms as soon
as 3 weeks (w) after starting T790Mi, only 1 p experienced an increase in pain,
but not related to bone M1. T790M was lost in 80% of the p and it was not
detected in serum at 3 or 6 w after the T790Mi initiation in 2 out of 4 and 4 out
of 7 evaluable p, respectively. Conclusion:
T790M detection can be lost early along T790Mi treatment.
The decrease in symptom burden is seen in p with loss of T790M.
PR and SD represent the BR in p with loss of T790M.
The loss of T790M in the serum may be a marker of symptomatic and
radiographic response to T790Mi.
Future evaluation would demonstrate if the reappearance of T790M mutation
in serum could be a marker of resistance to T790Mi.
Keywords: EGFR mutations, serum, T790M, Monitoring
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-015 IMPACT OF METASTATIC STATUS ON THE PROGNOSIS
OF PATIENTS TREATED WITH FIRST GENERATION EGFR-TKIS
Yoshihiko Taniguchi 1 , Akihiro Tamiya 1 , Kanako Katayama 1 , Tsunehiro Tanaka 1 ,
Kenji Nakahama 1 , Nobuhiko Saijo 1 , Yoko Naoki 1 , Masaki Kanazu 2 , Naoki
Omachi 1 , Kyoichi Okishio 3 , Takahiko Kasai 4 , Shinji Atagi 3
1 Depertment of Internal Medicine, National Hospital Organization Kinki-Chuo
Chest Medical Center, Sakai/Japan, 2 Depertment of Internal Medicine, National
Hospital Organization Toneyama National Hospital, Toyonaka/Japan, 3 Depertment
of Clinical Research Center, National Hospital Organization Kinki-Chuo Chest
Medical Center, Sakai/Japan, 4 Department of Pathology, National Hospital
Organization Kinki-Chuo Chest Medical Center, Sakai/Japan
Background: First generation epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitors (TKIs) such as gefitinib (GEF) or erlotinib (ERL)
are effective for patients harboring EGFR mutations positive non-small cell
lung cancer (NSCLC). To know the impact of metastatic status on patients
treated with EGFR-TKIs is important. The objective of this study is to know
the impact of metastatic status including brain metastasis, bone metastasis,
liver metastasis and pleural effusion on the prognosis of patients treated
with first generation EGFR-TKIs. Methods: The pathology files of National
Hospital Organization Kinki-chuo Chest Medical Center from 2009 to 2014
were retrospectively reviewed and 533 patients were EGFR mutation positive
NSCLC. Patients with stage IA to IIIA and small cell lung cancer were excluded.
From 299 stage IIIB, IV and relapsed NSCLC patients, 178 patients treated
with GEF or ERL as first line treatment were enrolled for the study. Metastatic
status, progression free survival (PFS), overall survival (OS) and response
rate (RR) were investigated. We also evaluated the relationship between the
number of metastatic organs and prognosis. Results: Fifty-one patients were
male and median age at the time of first line treatment was 72 years (range
39-91). Number of patients with adenocarcinoma was 168 and 156 patients
were treated with GEF. In log-rank test, PFS and OS were significantly worse
in patients with brain metastasis (8.0m vs 13.2m, p= 0.008; 20.2m vs 38.0m,
p< 0.001 respectively), bone metastasis (8.8m vs 15.4m, p< 0.001; 24.0m vs
32.1m, p= 0.020 respectively), liver metastasis (6.7m vs 12.5m, p< 0.001; 13.4m
vs 32.1m, p< 0.001 respectively) and pleural effusion (10.8m vs 12.2m, p= 0.033;
21.9m vs 34.9m, p= 0.004 respectively) at the time of first line treatment
compared with patients without each metastasis. In cox proportional hazards
models multivariate analysis, bone metastasis had correlated with worse PFS
(HR 2.110, 95%CI 1.437-3.093, p< 0.001) and moreover, brain metastasis had
correlated with worse OS (HR 2.414, 95%CI 1.464-3.951, p< 0.001). There were
no relationships between metastatic status and RR. Furthermore, the much
number of metastasized organs (no metastasis, 1 metastasis and 2 or more
metastasis) was significantly related to worse PFS (19.3m vs 12.5m vs 6.6m, p<
0.001) and OS (46.1m vs 29.9m vs 15.1m, p< 0.001). Conclusion: Bone metastasis
had correlated with worse PFS and brain metastasis had correlated with
worse OS in patients treated with first generation EGFR-TKIs. Moreover, the
much number of metastasized organs was related to worse PFS and OS.
Keywords: EGFR-TKI, metastasis, EGFR, NSCLC
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-016 AN EXPLORATION STUDY OF MECHANISMS
UNDERLYING PRIMARY RESISTANCE TO EGFR-TKIS IN PATIENTS
HARBORING TKI-SENSITIVE EGFR MUTATIONS
Ee Ke, Zhihong Chen, Jian Su, Xu-Chao Zhang, Longhua Guo, Feiyu Niu, Qiuyi
Zhang, Chongrui Xu, Yi Long Wu, Qing Zhou
Guangdong Lung Cancer Institute; Guangdong General Hospital(GGH)& Guangdong
Academy of Medical Sciences, Guangzhou/China
Background: Primary resistance to EGFR-TKIs was generally defined as disease
progression in less than 3 months without any evidence of objective response.
Although possible mechanisms have been investigated in several preclinical
and retrospective studies, little is known about the molecular backgrounds of
primary resistance. Methods: Random Sample of Cases was used to screen
TKI-sensitive patients to match with the primary resistant patients on the
basis of clinical characteristics (smoking history, EGFR mutations etc.). DNA
Copyright © 2016 by the International Association for the Study of Lung Cancer
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