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P1.02-014 HER2 Mutations in Chinese Patients with Non-Small Cell Lung Cancer
S494
observed. The frequency of gene abnormality was lower in VIA than non-VIA patients (48.4% vs.74.7%, P¼0.0015). No recurrence free survival difference existed in the VIA and non-VIA patients (38.0 vs.47.0 months, P¼0.524). A trend of worse overall survival in VIA than those with non-VIA patients was found (48.0vs.57.0 months, P¼0.052). Conclusion: VIA is rare in lung adenocarcinoma with lower frequency of common gene abnormality. Invasive mucinous adenocarcinoma was the most frequent subtype and KRAS was a predominant actionable mutation in VIA patients. A trend of worse survival existed in VIA than non-VIA patients. Keywords: non-small cell lung cancer, survival, variants of invasive adenocarcinoma, gene abnormality
P1.02-013 Clinicopathological Characteristics and Survival of ALK, ROS1 and RET Arrangements in Non-Adenocarcinoma Non-Small Cell Lung Cancer Patients
Journal of Thoracic Oncology
Vol. 12 No. 1S
adenosquamous carcinoma, squamous cell carcinoma, and large cell carcinoma were 8.2%, 1.6% and 1.8%, respectively. The median age of 12 patients was 49.5 years and three patients had smoking history. No survival difference existed between fusion genes positive and negative patients (36.7 vs.50.2 months, P¼0.21). Conclusion: The frequencies of ALK, ROS1 and RET rearrangements are low in non-adenocarcinoma NSCLC patients, and the clinical characteristics are similar with those in lung adenocarcinoma. Fusions of the three genes are not prognostic marker for non-adnocarcinoma NSCLC patients. Keywords: fusion gene, frequency, survival, non-small cell lung cancer
P1.02-014 HER2 Mutations in Chinese Patients with Non-Small Cell Lung Cancer Topic: Driver Genes in NSCLC, Resistance, and Other
Topic: Driver Genes in NSCLC, Resistance, and Other
Zhengbo Song, Yiping Zhang Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China
Zhengbo Song,1 Xinmin Yu,2 Yiping Zhang2 1Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer Hospital, Hangzhou/China
Background: ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear.
Background: ALK, ROS1 and RET rearrangements represent three most frequency of fusion genes in nonsmall cell lung cancer (NSCLC). Rearrangements of the three genes are predominantly found in lung adenocarcinoma，while,rare in non-adenocarcinoma. The aim of this study was to investigate the frequency, clinicopathological characteristics and survival of ALK, ROS1 and RET arrangements in non-adenocarcinoma NSCLC patients. Methods: We screened ALK, ROS1, and RET arrangements in patients with completely resected non-adenocarcinoma NSCLC using reverse transcriptase polymerase chain reaction (PCR). All positive samples were confirmed with fluorescence in situ hybridization (FISH). Survival analysis was performed with KaplanMeier method and log-rank for comparison. Results: Totally, 385 patients, who underwent complete resection, including 245 with squamous cell carcinoma, 85 with adenosquamous carcinoma and 55 with large cell carcinoma were enrolled. Twelve patients were identified as harboring fusion genes, including seven with ALK, three with ROS1 and two with RET rearrangements. The frequencies of fusions in
Methods: Eight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH. Overall survival (OS) was evaluated using Kaplan-Meier methods and compared with log-rank tests. Results: Twenty-one cases carrying HER2 mutations were identified with a prevalence of 2.4%. HER2 mutations were more frequently encountered in females, nonsmokers and adenocarcinoma. NGS was performed in 19 out of 21 patients, The results showed 16 cases with additional genetic aberrations, most commonly associated with TP53 (n ¼ 6), followed by EGFR (n ¼ 3), NF1 (n ¼ 3), KRAS (n ¼ 2) and other mutations. One patient harbored HER2 amplification (figure 1). Four patients with stage IV received afatinib treatment, and three showed stable disease with a median progression-free survival of 4 months and one patient was diagnosed with progressive disease. No survival difference existed between HER2 positive and negative patients (49.3 months vs.45.0 months, P ¼ 0.150).
January 2017
Conclusion: HER2 mutations represent a distinct subset of NSCLC. NGS showed that HER2 mutations commonly co-existed with other driver genes. Afatinib treatment displayed moderate efficacy in patients with HER2 mutations.
Abstracts
S495
showed a inferior efficacy of targeted therapy than those with accordance. Keywords: Epidermal growth factor receptor, Anaplastic lymphoma kinase, malignant pleural effusion, Non‒ small-cell lung cancer
Keywords: PREVALENCE, treatment, HER2 mutation, genetic variability
P1.02-015 A Multicenter Study of EGFR and EML4ALK Detection in Non-Squamous, Non‒ Small-Cell Lung Cancer Patients with Malignant Pleural Effusion Topic: Driver Genes in NSCLC, Resistance, and Other Xun Shi,1 Zhengbo Song,2 Xinmin Yu,1 Yiping Zhang1 Zhejiang Cancer Hospital, Hangzhou/China, 2Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China
1
Background: Currently, multicenter studies involving a large number of patients have not been not undertaken to detect the frequencies of EGFR mutations and ALK rearrangement in malignant pleural effusion (MPE) samples of patients with non-squamous, non‒small-cell lung cancer (NSCLC), we undertook a multicenter, observational study of Asian patients with untreated stage IV NSCLC. Methods: Eligible patients had untreated of EGFR and ALK inhibitor stage IV non-squamous NSCLC patients with MPE. The EGFR and ALK status of MPE and partially paired tumor tissue was determined with reverse transcription polymerase chain reaction (RT-PCR). Results: Among 210 patients with pleural effusion samples confirmed as malignant, 16 had EML4-ALK fusion gene rearrangements and 89 had EGFR mutations. No ALK/EGFR co-altered gene was found. Tumor tissue of 56 patients was collected. EGFR and ALK concordance rates between MPE samples and matched tumor tissue samples from 56 patients were 87.5% (49/56) and 96.1% (49/51), respectively. There was a tendency for a longer progression free survival in patients with EGFR accordance in comparison with those with EGFR discordance between tumor tissue and MPE samples (9.8 vs 6.2 months, respectively; p ¼ 0.078). A same trend was found in patients with ALK accordance and discordance (10.0 vs 3.2 months, respectively; p ¼ 0.004). Conclusion: These results demonstrate that MPE can be substituted for tumor tissues for EGFR and ALK gene detection. Patients with gene mutations or arrangement discordance between tumor tissue and MPE samples
P1.02-016 HER4 Expression Was Related to the Sensitivity of EGFR-TKI in Non-Small Cell Lung Cancer Topic: Driver Genes in NSCLC, Resistance, and Other Masaaki Inoue, Junichi Yoshida, Takashi Iwanami, Yusuke Nabe, Masatoshi Kanayama, Daisei Yasuda Chest Surgery, Shimonoseki City Hospital, Shimonoseki/ Japan Background: EGFR-TKIs show significant therapeutic effects against non-small cell lung cancer (NSCLC) with EGFR-activating mutations, however 20-30% of them have no response to EGFR-TKIs. HER-family receptors play a critical role in tumor progression, differentiation and survival in lung cancer. Recent studies suggest that the overexpression of HER-family receptors have a potential risk of EGFR-TKIs resistance. The aims of this study were to investigate the association between EGFRmutation and the expression of HER-family receptor in regard to clinical outcomes. Methods: We invested EGFR mutation by direct PCR analysis and HER2-4 expression by immunohistochemistry (IHC) of 231 consecutive non-small cell lung cancers, who had undertaken an operation from January 2007 to July 2012. The intensity of HER2-4 was graded (score: 0-3) from negative (score: 0-1) to positive (score: 2-3). The observed protein expression levels were analyzed for correlation to EGFR mutation status, clinicopathological parameters and the responses of EGFRTKI treatment. Results: EGFR mutation was observed in 40% of lung cancer, 61% of p. [Leu858Arg] and 31% of exon 19 deletion. Positive expression rates of HER2, HER3 and HER4 were 22.9%, 1.2%, 38.5%, respectively. HER4 positive rare of EGFR positive group was significantly higher than that of EGFR negative group (52% vs 30%, P<0.01), however there was no difference in HER2 expression. In histological type, positive rates of HER2 and HER4 in adenocarcinoma were higher than that in squamous cell carcinoma (HER2: 26% vs 13%, P¼0.07, HER4: 49% vs 13%, P<0.01). HER4 positive rate of HER2 positive group was significantly lower that of
observed. The frequency of gene abnormality was lower in VIA than non-VIA patients (48.4% vs.74.7%, P¼0.0015). No recurrence free survival difference existed in the VIA and non-VIA patients (38.0 vs.47.0 months, P¼0.524). A trend of worse overall survival in VIA than those with non-VIA patients was found (48.0vs.57.0 months, P¼0.052). Conclusion: VIA is rare in lung adenocarcinoma with lower frequency of common gene abnormality. Invasive mucinous adenocarcinoma was the most frequent subtype and KRAS was a predominant actionable mutation in VIA patients. A trend of worse survival existed in VIA than non-VIA patients. Keywords: non-small cell lung cancer, survival, variants of invasive adenocarcinoma, gene abnormality
P1.02-013 Clinicopathological Characteristics and Survival of ALK, ROS1 and RET Arrangements in Non-Adenocarcinoma Non-Small Cell Lung Cancer Patients
Journal of Thoracic Oncology
Vol. 12 No. 1S
adenosquamous carcinoma, squamous cell carcinoma, and large cell carcinoma were 8.2%, 1.6% and 1.8%, respectively. The median age of 12 patients was 49.5 years and three patients had smoking history. No survival difference existed between fusion genes positive and negative patients (36.7 vs.50.2 months, P¼0.21). Conclusion: The frequencies of ALK, ROS1 and RET rearrangements are low in non-adenocarcinoma NSCLC patients, and the clinical characteristics are similar with those in lung adenocarcinoma. Fusions of the three genes are not prognostic marker for non-adnocarcinoma NSCLC patients. Keywords: fusion gene, frequency, survival, non-small cell lung cancer
P1.02-014 HER2 Mutations in Chinese Patients with Non-Small Cell Lung Cancer Topic: Driver Genes in NSCLC, Resistance, and Other
Topic: Driver Genes in NSCLC, Resistance, and Other
Zhengbo Song, Yiping Zhang Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China
Zhengbo Song,1 Xinmin Yu,2 Yiping Zhang2 1Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer Hospital, Hangzhou/China
Background: ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear.
Background: ALK, ROS1 and RET rearrangements represent three most frequency of fusion genes in nonsmall cell lung cancer (NSCLC). Rearrangements of the three genes are predominantly found in lung adenocarcinoma，while,rare in non-adenocarcinoma. The aim of this study was to investigate the frequency, clinicopathological characteristics and survival of ALK, ROS1 and RET arrangements in non-adenocarcinoma NSCLC patients. Methods: We screened ALK, ROS1, and RET arrangements in patients with completely resected non-adenocarcinoma NSCLC using reverse transcriptase polymerase chain reaction (PCR). All positive samples were confirmed with fluorescence in situ hybridization (FISH). Survival analysis was performed with KaplanMeier method and log-rank for comparison. Results: Totally, 385 patients, who underwent complete resection, including 245 with squamous cell carcinoma, 85 with adenosquamous carcinoma and 55 with large cell carcinoma were enrolled. Twelve patients were identified as harboring fusion genes, including seven with ALK, three with ROS1 and two with RET rearrangements. The frequencies of fusions in
Methods: Eight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH. Overall survival (OS) was evaluated using Kaplan-Meier methods and compared with log-rank tests. Results: Twenty-one cases carrying HER2 mutations were identified with a prevalence of 2.4%. HER2 mutations were more frequently encountered in females, nonsmokers and adenocarcinoma. NGS was performed in 19 out of 21 patients, The results showed 16 cases with additional genetic aberrations, most commonly associated with TP53 (n ¼ 6), followed by EGFR (n ¼ 3), NF1 (n ¼ 3), KRAS (n ¼ 2) and other mutations. One patient harbored HER2 amplification (figure 1). Four patients with stage IV received afatinib treatment, and three showed stable disease with a median progression-free survival of 4 months and one patient was diagnosed with progressive disease. No survival difference existed between HER2 positive and negative patients (49.3 months vs.45.0 months, P ¼ 0.150).
January 2017
Conclusion: HER2 mutations represent a distinct subset of NSCLC. NGS showed that HER2 mutations commonly co-existed with other driver genes. Afatinib treatment displayed moderate efficacy in patients with HER2 mutations.
Abstracts
S495
showed a inferior efficacy of targeted therapy than those with accordance. Keywords: Epidermal growth factor receptor, Anaplastic lymphoma kinase, malignant pleural effusion, Non‒ small-cell lung cancer
Keywords: PREVALENCE, treatment, HER2 mutation, genetic variability
P1.02-015 A Multicenter Study of EGFR and EML4ALK Detection in Non-Squamous, Non‒ Small-Cell Lung Cancer Patients with Malignant Pleural Effusion Topic: Driver Genes in NSCLC, Resistance, and Other Xun Shi,1 Zhengbo Song,2 Xinmin Yu,1 Yiping Zhang1 Zhejiang Cancer Hospital, Hangzhou/China, 2Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China
1
Background: Currently, multicenter studies involving a large number of patients have not been not undertaken to detect the frequencies of EGFR mutations and ALK rearrangement in malignant pleural effusion (MPE) samples of patients with non-squamous, non‒small-cell lung cancer (NSCLC), we undertook a multicenter, observational study of Asian patients with untreated stage IV NSCLC. Methods: Eligible patients had untreated of EGFR and ALK inhibitor stage IV non-squamous NSCLC patients with MPE. The EGFR and ALK status of MPE and partially paired tumor tissue was determined with reverse transcription polymerase chain reaction (RT-PCR). Results: Among 210 patients with pleural effusion samples confirmed as malignant, 16 had EML4-ALK fusion gene rearrangements and 89 had EGFR mutations. No ALK/EGFR co-altered gene was found. Tumor tissue of 56 patients was collected. EGFR and ALK concordance rates between MPE samples and matched tumor tissue samples from 56 patients were 87.5% (49/56) and 96.1% (49/51), respectively. There was a tendency for a longer progression free survival in patients with EGFR accordance in comparison with those with EGFR discordance between tumor tissue and MPE samples (9.8 vs 6.2 months, respectively; p ¼ 0.078). A same trend was found in patients with ALK accordance and discordance (10.0 vs 3.2 months, respectively; p ¼ 0.004). Conclusion: These results demonstrate that MPE can be substituted for tumor tissues for EGFR and ALK gene detection. Patients with gene mutations or arrangement discordance between tumor tissue and MPE samples
P1.02-016 HER4 Expression Was Related to the Sensitivity of EGFR-TKI in Non-Small Cell Lung Cancer Topic: Driver Genes in NSCLC, Resistance, and Other Masaaki Inoue, Junichi Yoshida, Takashi Iwanami, Yusuke Nabe, Masatoshi Kanayama, Daisei Yasuda Chest Surgery, Shimonoseki City Hospital, Shimonoseki/ Japan Background: EGFR-TKIs show significant therapeutic effects against non-small cell lung cancer (NSCLC) with EGFR-activating mutations, however 20-30% of them have no response to EGFR-TKIs. HER-family receptors play a critical role in tumor progression, differentiation and survival in lung cancer. Recent studies suggest that the overexpression of HER-family receptors have a potential risk of EGFR-TKIs resistance. The aims of this study were to investigate the association between EGFRmutation and the expression of HER-family receptor in regard to clinical outcomes. Methods: We invested EGFR mutation by direct PCR analysis and HER2-4 expression by immunohistochemistry (IHC) of 231 consecutive non-small cell lung cancers, who had undertaken an operation from January 2007 to July 2012. The intensity of HER2-4 was graded (score: 0-3) from negative (score: 0-1) to positive (score: 2-3). The observed protein expression levels were analyzed for correlation to EGFR mutation status, clinicopathological parameters and the responses of EGFRTKI treatment. Results: EGFR mutation was observed in 40% of lung cancer, 61% of p. [Leu858Arg] and 31% of exon 19 deletion. Positive expression rates of HER2, HER3 and HER4 were 22.9%, 1.2%, 38.5%, respectively. HER4 positive rare of EGFR positive group was significantly higher than that of EGFR negative group (52% vs 30%, P<0.01), however there was no difference in HER2 expression. In histological type, positive rates of HER2 and HER4 in adenocarcinoma were higher than that in squamous cell carcinoma (HER2: 26% vs 13%, P¼0.07, HER4: 49% vs 13%, P<0.01). HER4 positive rate of HER2 positive group was significantly lower that of