Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
our institution. Results: A total of 539 patients were enrolled in this study
with a median progression-free survival time (PFS) of 11.1 months according
to RECIST criteria. In all, 297 (55.1%) patients underwent rebiopsy for 178
computed tomography (CT)-guided needle biopsies, 87 serous cavity effusion
(including 80 pleural effusion, 3 ascitic fluid and 4 pericardial effusion), 21
superficial lymph node biopsy, 11 other procedures. 354 (65.7%) patients
after EGFR-TKIs failure were performed EGFR mutation testing used by
288 rebiopsy and 66 plasma samples. 181 (51.5%) had T790M mutation. In
66 plasma samples, 29 (43.9%) hardored T790M mutation, 23 (34.8%) with
mutation in accordance with before EGFR-TKIs treatment, 14 with wildtype
EGFR. In all patients, 341 recieved further treatment in our hospital;
236 (69.2%) patients treated with chemotherapy, 43 (12.6%) recieved TKI
combined local treatment, 42 (12.3%) changed second or third generation
TKIs, 30 switched to other treament. But this part of data still underdone.
Conclusion: Rebiopsy is feasible in patients after EGFR-TKIs failure. Rebiopsy
could effect on further treatment strategies after especially third generarion
EGFR-TKI in clinical application. While plasma is also an available surrogate
of EGFR mutation testing for patients without suitable lesions for rebiopsy
after disease progression.
TKI failure. All patients with plasma EGFR testing done using ddPCR
technique from Nov 2015 to Mar 2016 are retrospectively identified and
analyzed. Results: 47 patients were tested for EGFR mutations by ddPCR after
EGFR TKI failure. 19 patients had detectable T790M mutant copies of 3.5 -
65887.3 mutant copies/ml plasma (median 61.5). All had previous use of TKI > 6
months (range 171 – 1592 day, median 544). Among the 14 patients who
received osimertinib, the median PFS and OS were not reached over a mean
follow up of 4.3 months. There was one progressive disease, five stable
diseases and eight partial responses as the best treatment response. The
number of T790M mutant copies number/ml plasma in the PR group was
numerically higher than the SD/PD group (mean 416.5 vs 25.9) but statistically
insignificant (p-value 0.15) for difference. Of the limited eight patients having
simultaneous tissue biopsy and molecular testing in this cohort, six was
concordant with the plasma EGFR result. The two remaining had detectable
T790M in plasma EGFR but not in tissue re-biopsy, and, of note, one achieved
partial response and one stable disease after osimertinib.
Keywords: rebiopsy, non-small cell lung cancer, EGFR-TKI, EGFR mutation
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-105 MUTATIONAL PROFILING OF NON-SMALL-CELL
LUNG CANCER PATIENTS RESISTANT TO FIRST-GENERATION
EGFR TYROSINE KINASE INHIBITORS USING NEXT GENERATION
SEQUENCING
Ying Jin, Xinmin Yu, Xun Shi, Yiping Zhang, Guangyuan Lou
Zhejiang Cancer Hospital, Hangzhou/China
Background: Patients with advanced non-small-cell lung cancer (NSCLC)
harboring sensitive epithelial growth factor receptor (EGFR) mutations
invariably develop acquired resistance to EGFR tyrosine kinase inhibitors
(TKIs). Although previous research have identified several mechanisms of
resistance, the systematic evaluation using next generation sequencing (NGS)
to establish the genomic mutation profiles at the time of acquired resistance
has not been conducted. Methods: In our single center, we performed NGS
of a pre-defined set of 416 cancer-related genes in a cohort of 97 patients
with NSCLC harboring TKI-sensitive EGFR mutations at the time of acquired
resistance to first-generation EGFR-TKIs between January 2015 to December
2015. Results: In 97 samples we found total 345 gene alterations (mean 3.6
mutations per patient, range 1-10). Fifty-six patients (57.7%) still exhibit
EGFR-sensitive mutations as pretreatment, 93 patients (95.9%) exhibit at
least one mutation except for previous existed EGFR-sensitive mutations. In
all the 97 patients, most frequently mutated genes were TP53 (59.8%), T790M
(28.9%), TET2 (11.3%), EGFR amplification (10.3%), PIK3CA (8.2%), BIM (8.2%),
KRAS (7.2%), APC (7.2%), RB1 (7.2%), HER2 (6.2%), DNMT3A (6.2%) and MET
(5.2%). Conclusion: NGS in this study uncovered many new genetic alterations
potentially associated with EGFR TKI resistance and provided information
for the further study of drug resistance and corresponding relevant tactics
against the challenge of disease progression.
Keywords: non-small cell lung cancer, epithelial growth factor receptor,
Tyrosine kinase inhibitors, drug resistance
Conclusion: Plasma-EGFR-directed osimertinib treatment using ddPCR
technique is feasible. The technique quantifies mutant load with potential
prognostic implication, and detects heterogeneous tumors who might benefit
from osimertinib despite negative tissue biopsy result.
Keywords: ddPCR, plasma EGFR, Tumor heterogeneity, osimertinib
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR RES –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-106 LOCAL EXPERIENCE OF OSIMERTINIB USE;
RETROSPECTIVE REVIEW BASED ON PLASMA EGFR USING DDPCR
TECHNIQUE
Jacky Li 1 , Elizabeth Chuk 1 , Stanley Lee 1 , Eugenie Hui 2 , Joseph S K Au 1
1 Clinical Oncology, Queen Elizabeth Hospital, Hong Kong/Hong Kong Prc,
2 Medicine, Queen Elizabeth Hospital, Hong Kong/Hong Kong Prc
Background: Osimertinib was approved by FDA in Nov 2016 for treatment of
patients with metastatic EGFR-T790M mutation positive NSCLC, as detected
by an FDA-approved test (Cobas ® EGFR Mutation Test v2) after EGFR-TKI
failure, with an ORR up to 70% and a PFS around 11 months. Methods: We
report local experience on EGFR mutations detected by droplet digital
polymerase chain reaction (ddPCR) technique on cell free tumor DNA from
lung cancer patients, guiding osimertinib therapy after 1 st or 2 nd generation
P3.02B-107 EFFICACY OF AFATINIB AND GEFITINIB IN LUNG
ADENOCARCINOMA WITH EGFR GENE MUTATION AS 2ND OR 3RD
LINE TREATMENT
Marisol Arroyo Hernandez 1 , Jerónimo Rodríguez Cid 2 , Jorge Alatorre
Alexander 2 , José Escobar-Penagos 2 , Julio Garibay-Diaz 2
1 Pulmonary Medicine, Instituto Nacional de Enfermedades Respiratorias Ismael
Cosío Villegas, Mexico City/Mexico, 2 Medical Oncology, Instituto Nacional de
Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City/Mexico
Background: In Mexico, 85% of patients with lung cancer are diagnosed in
an advanced stage. The most effective current treatment is chemotherapy,
however only 40% of patients respond to it. A substantial progress is the
recognition of several distinct subgroups of Adenocarcinoma that respond
differently according to mutations in oncogenes. Patients with EGFR
mutation are optimally treated with EGFR tyrosine kinase inhibitors (TKIs).
In Mexico, the access to oncologic medication is problematic due to poverty,
socio-demographic problems and health access, which impedes treatment
initiation with TKIs as first line therapy. We sought to confirm the beneficial
effect of TKIs as second or third line therapy on patients with advanced stage
S660 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017