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J.A. Hwang
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-012 - Clinical Implications of Isolated Bone Failure without Systemic Disease Progression During EGFR-TKI Treatment (ID 1201)
09:30 - 17:00 | Author(s): J.A. Hwang
- Abstract
Background:
Bone metastasis and skeletal-related events (SREs) such as pathologic fracture and spinal cord compression are common in advanced lung cancer. This study was aimed to investigate the characteristics of disease progression focused on SREs during EGFR-TKI treatment.
Methods:
We retrospectively reviewed the medical records of 3,085 Korean patients with advanced non-small cell lung cancer who were treated with gefitinib or erlotinib between 2004 and 2014. SRE associated with aggravation of bone metastasis was termed ‘bone failure (BF)’. BFs were classified into 2 categories according to the presence of accompanying disease progression of preexisting cancer lesions in extra-skeletal organs; isolated bone failure (IBF) versus non-IBF.
Results:
The incidence of SREs during EGFR-TKI treatment was 4.7% (146/3085). Among them, 60 patients experienced IBF without aggravation of disease in extra-skeletal organs. IBF was more frequent in clinical benefit group (responders and stable ≥ 6 months) than in non-clinical benefit group (53.5% vs 13.3%; P < 0.001). Adenocarcinoma histology and clinical benefit from EGFR-TKI were independent risk factors for IBF (adenocarcinoma: adjusted hazard ratio [HR] 10.283; 95% confidence interval [CI] 1.148 – 92.121; P= 0.037, clinical benefit from TKI: adjusted HR 9.463; 95% CI 3.027 – 29.584; P < 0.001). The time from the start of EGFR-TKI to the occurrence of SRE was significantly longer in IBF than that in non-IBF (9.8 vs 5.2 months; P= 0.054). Moreover, patients with IBF exhibited longer survival time from the initiation of TKI (20.1 vs 7.7 months; P = 0.008) and from the occurrence of SRE (9.2 vs 1.9 months; P = 0.006). Multivariate analysis showed that IBF was one of independent prognostic factors for better survival although the statistical significance was marginal (adjusted HR 0.492; 95% CI 0.237 – 1.021; P = 0.057).
Conclusion:
IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI treatment and shows the better survival requiring more active treatment.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-035 - Genetic Heterogeneity of Actionable Genes between Primary and Metastatic Tumor in Lung Adenocarcinoma (ID 676)
09:30 - 17:00 | Author(s): J.A. Hwang
- Abstract
Background:
Because procedures obtaining lung cancer tissues involve high probability of critical complication, biopsies are usually done at a site of easy access. Authors questioned whether genetic information obtained at one biopsy site represent that of other lesion and is sufficient for therapeutic decision.
Methods:
Forty-one matched non-small cell lung cancer (NSCLC) samples of primary tumor and metastatic lymph node (L/N) were randomly selected from institutional tissue archives. non-synonymous mutation and ins-del of 16 genes that contain actionable mutations, intron 2 deletion polymorphism of Bcl2-like11, and copy number variation (CNV) of MET and FGFR1 were analyzed by NGS based technique.
Results:
A total 251 mutations, including 217 non-synonymous mutations, 30 deletions, and 4 insertions were discovered in this study. There were higher chances to discover non-synonymous mutations in the primary tumor than in the metastatic L/N (140 (64.5 %) vs. 77 (35.5%)). In the primary tumor, 106 G>A: C>T transitions (75.7%) out of 140 non-synonymous mutation were detected, whereas in the metastatic L/N 44 (57.1%) out of 77 were discovered, showing decrease of G>A: C>T transition in the L/N metastatic lesion. The proportion of C>G: G>C and C>T: G>A was 80.7% in the primary tumor and 67.5% in the metastatic L/N, showing APOBEC activity in the metastatic L/N was not prominent in this study model. When the mutation profile between primary and metastatic lesion were compared, 28 out of 41 (68.3%) cases showed identical mutation profiles whereas 13 (31.7%) showed discrepancy. Fifty out of 82 tested samples showed CNV of either FGFR1 or MET and 24 out of 41 cases showed discrepancy of copy numbers of tested genes between primary tumor and metastatic L/N.
Conclusion:
The genetic heterogeneity between the primary tumor and lymph node metastatic lesions are significant findings to consider when designing a therapeutic plan from a result of one site inspection. A large prospective study is needed to evaluate the impact of genetic heterogeneity on the clinical outcome of NSCLC patients.
