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A multicenter study of NRG1 fusions in Chinese non-small cell lung cancer patients and response to afatinib using next generation sequencing
abstracts
Annals of Oncology
of interest.
526P
A phase II study of apatinib in patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC)
L. Chu1, F. Liang2, J. Zhang1, J. Deng1, Y. Chen1, Q. Liu1, D. Ai1, Z. Zhu1, K. Zhao1 Radiation Oncology, Shanghai Cancer Center Fudan University, Shanghai, China, 2 Clinical Statistics Center, Shanghai Cancer Center Fudan University, Shanghai, China
NRG1 fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, only one (0.04%) patient was identified with a CD74NRG1 fusion. The patient was a 55-year-old never smoking male, who was diagnosed with lung adenocarcinoma from biopsies obtained, CD74-NRG1 fusion was found by NGS, the genes co-altered with NRG1 fusion was no concurrent with KRAS, EGFR, ALK, ROS1, RET, or other known drivers were identified in the study cohort cases, and NRG1 fusion driven NSCLC responding to afatinib will be presented. The patient was considered to have a partial response (PR) to afatinib, and he was alive up to now. Conclusions: NRG1 fusions were detected at a low incidence (0.04%) in Chinese patients. Patients with advanced NRG1 fusion NSCLC showed a good outcome of afatinib compared to those with ALK/ROS1 fusion which response to crizotinib, which will influence the development of strategies to detect these events on a large scale. Legal entity responsible for the study: Xingliang Li. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1
528P Background: No standard treatment strategy for patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC) experiencing progression after one or more lines of chemotherapy. The aim of this study was to assess the efficacy and safety of apatinib, an oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, in patients with recurrent/metastatic ESCC for whom at least one line of prior chemotherapy had failed. Methods: This was a phase II trial that enrolled patients with recurrent/metastatic ESCC who had evidence of disease progression after first-line or more lines chemotherapy. All patients received continuous apatinib 500mg once daily until disease progression, death, or intolerable toxicity, dose escalation was allowed. The primary end point was progression free survival (PFS). Results: Between July 2017 and August 2018, 40 patients were recruited. Data was cutoff at June 26, 2019. Among the 40 patients, 5 patients achieved partial response while 21 had stable disease. Primary end point median PFS (mPFS) was 113 days (95% 45-180). Median OS (mOS) was 158 days (95% 101-215), Objective response rate (ORR) was 12.5%. The incidence of drug-related adverse events (AEs) was 87.5%. 40.0% patients developed severe AEs. Main AEs were Fatigue (37.5%), Hand-foot syndrome (27.5%) and Hypertension (25%). Two patients with massive hemoptysis, and two patients with tracheal esophageal fistula had the uncontrolled primary tumor or trachea/bronchi eroded. Conclusions: The study confirmed that apatinib was effective as second-line or more lines treatment for recurrent/metastatic ESCC patients, and most adverse effect were acceptable. However, patients with uncontrolled primary tumor or trachea/bronchi eroded should been cautiously considered to use. Clinical trial identification: NCT03274011. Legal entity responsible for the study: Fudan University Shanghai Cancer Center. Funding: Jiangsu Hengrui Medicine. Disclosure: All authors have declared no conflicts of interest.
527P
A multicenter study of NRG1 fusions in Chinese non-small cell lung cancer patients and response to afatinib using next generation sequencing
X. Li1, W. Wang2, C. Xu3, X. Pu4, S. Fang5, X. Cai6, Y. Fang7, Y. Zhu8, H. Wang9, X. Liang10, W. Zhuang11, Y. Zhang12, L. Wang13, X. Cai14, J. Li15, H. Feng16, M. Fang2, G. Chen3, T. Lv17, Y. Song17 1 Tumor Molecular Laboratory, Zhejiang Rongjun Hospital, Jiaxing, China, 2 Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, China, 3Pathology, Fujian Cancer Hospital, Fuzhou, China, 4Thoracic Medical Oncology II, Hunan Cancer Hospital, Changsha, China, 5Pathology, Daping Hospital and Research Institute of Surgery, Army Medical University, Chongqing, China, 6Oncology, Sun Yat-sen University Cancer Hospital, Guangzhou, China, 7Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China, 8Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing, China, 9Lung Cancer, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China, 10Oncology, The Third People’s Hospital of Zhengzhou, Zhengzhou, China, 11Medical Oncology, Fujian Cancer Hospital, Fuzhou, China, 12Oncology, The Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China, 13 Oncology, Baotou Cancer Hospital, Baotou, China, 14Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China, 15Radiotherapy, Xiamen Cancer Hospital, Xiamen, China, 16Oncology, Shanxi Dayi Hospital, Shanxi Academy of Medical Science, Taiyuan, China, 17Respiratory Medicine, Jinling Hospital, Nanjing, China Background: NRG1 fusions are potentially actionable genomic events seen in nonsmall cell lung cancers (NSCLC) and there are reports of therapeutic efficacy with agents that target Erb-B2/Erb-B3, while little is known about NRG1 fusions association with outcomes of afatinib. The aim of this study was to investigate the efficacy of afatinib in patients with advanced NRG1 fusion NSCLC. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the
Volume 30 | Supplement 9 | November 2019
High-biologically effective dose radiotherapy may improve local control of small cell lung cancer patients with brain metastases: A propensity-matching analysis
Q. Zhuang1, F. Lin1, X. Lin1, J. Li2, W. Junxin1 Radiation Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China, 2 Radiotherapy, The First Affiliated Hospital of Xiamen University, Xiamen, China
1
Background: To compare the effects of high biologically effective dose (BED) and low BED radiotherapy for small cell lung cancer (SCLC) with brain metastases (BMs), and identify the prognostic factors of survival. Methods: A total of 250 consecutive limited-stage (LC) SCLC with BMs patients in our institution were retrospectively analyzed, from January 1998 to June 2018. Preliminary screening of the prognostic factors was accomplished by Kaplan-Meier univariate analysis. Baseline covariates were balanced by a propensity-matching analysis. And survival curves between two groups were compared by log-rank test. The Cox regression model was used to analyze factors associated with prognosis. Results: The Cutoff Finder program exported an optimal BED cutoff value of 47 for all patients. The high-BED (>47 Gy) group had a significantly better brain metastases progression-free survival (BMPFS) than low-BED (47 Gy) group (median BMPFS: 14.4 vs. 8.3, P < 0.001). Multivariate analysis found that BED, smoking and age (P < 0.001) were independently prognostic factors affecting BMPFS. And after 1:2 propensity score matching, 176 patients were divided into the high-BED group (n ¼ 59) and the lowBED group (n ¼ 117). In the matched cohort, BMPFS was significantly higher in the high-BED group than low-BED group (P < 0.001). Conclusions: BED, smoking and age were observed to affect BMPFS of SCLC patients with BMs. High BED radiotherapy (>47 Gy) might improve local control. Additional study is warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
529P
Osimertinib for patients with EGFR-mutant advanced NSCLC and asymptomatic brain metastases: An open-label, two-arm, phase II study
R. Gillis1, N. Peled1, I. Goldshtien1, O. Rotem2, A.B. Rozenblum2, H. Nechushtan3, L. Chen2, E. Dudnik2, A. Zer4, S. Yust-Katz2, I. Shelef5, L.C. Roisman1, E. Inbar2 1 Oncology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel, 2Oncology, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, Petah Tikva, Israel, 3Oncology, Hadassah Medical Center, Jerusalem, Israel, 4Medical Oncology, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, Petah Tikva, Israel, 5Radilology, Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel Background: Osimertinib is an EGFR TKI selective for both EGFR TKI sensitizing and Thr790Met resistance mutations. While intracranial activity of osimertinib has been observed in patient subgroups within larger trials, a study focusing exclusively on patients with brain metastases has not yet been reported. We assessed the intracranial activity of osimertinib in EGFR-mutant, NSCLC patients with asymptomatic brain metastases, either as first-line therapy or following progression in pre-treated Thr790Met-positive patients. Methods: In this phase 2, open-label, two-arm study we enrolled patients with EGFRmutant, metastatic NSCLC and at least one asymptomatic brain metastasis of 4 mm or larger in diameter. Treatment-naı¨ve patients (arm A) and Thr790Met-positive patients who progressed on EGFR-TKI therapy (arm B) received osimertinib 80 mg once daily. Dose escalation to 160 mg once daily was performed in cases of intracranial progression without symptomatic systemic progression. The primary endpoint in both arms was
doi:10.1093/annonc/mdz437 | ix177
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz437.052/5638368 by Goteborgs Universitet user on 14 December 2019
with previously reported chemotherapy regimen, CBDCA plus paclitaxel or Cisplatin combination chemotherapy. No treatment-related deaths occurred in this cohort. Grade 3 or worse hematological toxicity was observed in five patients (neutropenia: three patients; anemia: two patients); grade 3 or worse non-hematological toxicity was observed in three patients. None of the patients developed febrile neutropenia. Conclusions: Cisplatin and Irinotecan combination chemotherapy may be a safe and effective first-line chemotherapy regimen for unresectable thymic carcinoma. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: Y. Hosomi: Honoraria (self): AstraZeneca. All other authors have declared no conflicts
Annals of Oncology
of interest.
526P
A phase II study of apatinib in patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC)
L. Chu1, F. Liang2, J. Zhang1, J. Deng1, Y. Chen1, Q. Liu1, D. Ai1, Z. Zhu1, K. Zhao1 Radiation Oncology, Shanghai Cancer Center Fudan University, Shanghai, China, 2 Clinical Statistics Center, Shanghai Cancer Center Fudan University, Shanghai, China
NRG1 fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, only one (0.04%) patient was identified with a CD74NRG1 fusion. The patient was a 55-year-old never smoking male, who was diagnosed with lung adenocarcinoma from biopsies obtained, CD74-NRG1 fusion was found by NGS, the genes co-altered with NRG1 fusion was no concurrent with KRAS, EGFR, ALK, ROS1, RET, or other known drivers were identified in the study cohort cases, and NRG1 fusion driven NSCLC responding to afatinib will be presented. The patient was considered to have a partial response (PR) to afatinib, and he was alive up to now. Conclusions: NRG1 fusions were detected at a low incidence (0.04%) in Chinese patients. Patients with advanced NRG1 fusion NSCLC showed a good outcome of afatinib compared to those with ALK/ROS1 fusion which response to crizotinib, which will influence the development of strategies to detect these events on a large scale. Legal entity responsible for the study: Xingliang Li. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1
528P Background: No standard treatment strategy for patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC) experiencing progression after one or more lines of chemotherapy. The aim of this study was to assess the efficacy and safety of apatinib, an oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, in patients with recurrent/metastatic ESCC for whom at least one line of prior chemotherapy had failed. Methods: This was a phase II trial that enrolled patients with recurrent/metastatic ESCC who had evidence of disease progression after first-line or more lines chemotherapy. All patients received continuous apatinib 500mg once daily until disease progression, death, or intolerable toxicity, dose escalation was allowed. The primary end point was progression free survival (PFS). Results: Between July 2017 and August 2018, 40 patients were recruited. Data was cutoff at June 26, 2019. Among the 40 patients, 5 patients achieved partial response while 21 had stable disease. Primary end point median PFS (mPFS) was 113 days (95% 45-180). Median OS (mOS) was 158 days (95% 101-215), Objective response rate (ORR) was 12.5%. The incidence of drug-related adverse events (AEs) was 87.5%. 40.0% patients developed severe AEs. Main AEs were Fatigue (37.5%), Hand-foot syndrome (27.5%) and Hypertension (25%). Two patients with massive hemoptysis, and two patients with tracheal esophageal fistula had the uncontrolled primary tumor or trachea/bronchi eroded. Conclusions: The study confirmed that apatinib was effective as second-line or more lines treatment for recurrent/metastatic ESCC patients, and most adverse effect were acceptable. However, patients with uncontrolled primary tumor or trachea/bronchi eroded should been cautiously considered to use. Clinical trial identification: NCT03274011. Legal entity responsible for the study: Fudan University Shanghai Cancer Center. Funding: Jiangsu Hengrui Medicine. Disclosure: All authors have declared no conflicts of interest.
527P
A multicenter study of NRG1 fusions in Chinese non-small cell lung cancer patients and response to afatinib using next generation sequencing
X. Li1, W. Wang2, C. Xu3, X. Pu4, S. Fang5, X. Cai6, Y. Fang7, Y. Zhu8, H. Wang9, X. Liang10, W. Zhuang11, Y. Zhang12, L. Wang13, X. Cai14, J. Li15, H. Feng16, M. Fang2, G. Chen3, T. Lv17, Y. Song17 1 Tumor Molecular Laboratory, Zhejiang Rongjun Hospital, Jiaxing, China, 2 Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, China, 3Pathology, Fujian Cancer Hospital, Fuzhou, China, 4Thoracic Medical Oncology II, Hunan Cancer Hospital, Changsha, China, 5Pathology, Daping Hospital and Research Institute of Surgery, Army Medical University, Chongqing, China, 6Oncology, Sun Yat-sen University Cancer Hospital, Guangzhou, China, 7Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China, 8Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing, China, 9Lung Cancer, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China, 10Oncology, The Third People’s Hospital of Zhengzhou, Zhengzhou, China, 11Medical Oncology, Fujian Cancer Hospital, Fuzhou, China, 12Oncology, The Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China, 13 Oncology, Baotou Cancer Hospital, Baotou, China, 14Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China, 15Radiotherapy, Xiamen Cancer Hospital, Xiamen, China, 16Oncology, Shanxi Dayi Hospital, Shanxi Academy of Medical Science, Taiyuan, China, 17Respiratory Medicine, Jinling Hospital, Nanjing, China Background: NRG1 fusions are potentially actionable genomic events seen in nonsmall cell lung cancers (NSCLC) and there are reports of therapeutic efficacy with agents that target Erb-B2/Erb-B3, while little is known about NRG1 fusions association with outcomes of afatinib. The aim of this study was to investigate the efficacy of afatinib in patients with advanced NRG1 fusion NSCLC. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the
Volume 30 | Supplement 9 | November 2019
High-biologically effective dose radiotherapy may improve local control of small cell lung cancer patients with brain metastases: A propensity-matching analysis
Q. Zhuang1, F. Lin1, X. Lin1, J. Li2, W. Junxin1 Radiation Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China, 2 Radiotherapy, The First Affiliated Hospital of Xiamen University, Xiamen, China
1
Background: To compare the effects of high biologically effective dose (BED) and low BED radiotherapy for small cell lung cancer (SCLC) with brain metastases (BMs), and identify the prognostic factors of survival. Methods: A total of 250 consecutive limited-stage (LC) SCLC with BMs patients in our institution were retrospectively analyzed, from January 1998 to June 2018. Preliminary screening of the prognostic factors was accomplished by Kaplan-Meier univariate analysis. Baseline covariates were balanced by a propensity-matching analysis. And survival curves between two groups were compared by log-rank test. The Cox regression model was used to analyze factors associated with prognosis. Results: The Cutoff Finder program exported an optimal BED cutoff value of 47 for all patients. The high-BED (>47 Gy) group had a significantly better brain metastases progression-free survival (BMPFS) than low-BED (47 Gy) group (median BMPFS: 14.4 vs. 8.3, P < 0.001). Multivariate analysis found that BED, smoking and age (P < 0.001) were independently prognostic factors affecting BMPFS. And after 1:2 propensity score matching, 176 patients were divided into the high-BED group (n ¼ 59) and the lowBED group (n ¼ 117). In the matched cohort, BMPFS was significantly higher in the high-BED group than low-BED group (P < 0.001). Conclusions: BED, smoking and age were observed to affect BMPFS of SCLC patients with BMs. High BED radiotherapy (>47 Gy) might improve local control. Additional study is warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
529P
Osimertinib for patients with EGFR-mutant advanced NSCLC and asymptomatic brain metastases: An open-label, two-arm, phase II study
R. Gillis1, N. Peled1, I. Goldshtien1, O. Rotem2, A.B. Rozenblum2, H. Nechushtan3, L. Chen2, E. Dudnik2, A. Zer4, S. Yust-Katz2, I. Shelef5, L.C. Roisman1, E. Inbar2 1 Oncology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel, 2Oncology, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, Petah Tikva, Israel, 3Oncology, Hadassah Medical Center, Jerusalem, Israel, 4Medical Oncology, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, Petah Tikva, Israel, 5Radilology, Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel Background: Osimertinib is an EGFR TKI selective for both EGFR TKI sensitizing and Thr790Met resistance mutations. While intracranial activity of osimertinib has been observed in patient subgroups within larger trials, a study focusing exclusively on patients with brain metastases has not yet been reported. We assessed the intracranial activity of osimertinib in EGFR-mutant, NSCLC patients with asymptomatic brain metastases, either as first-line therapy or following progression in pre-treated Thr790Met-positive patients. Methods: In this phase 2, open-label, two-arm study we enrolled patients with EGFRmutant, metastatic NSCLC and at least one asymptomatic brain metastasis of 4 mm or larger in diameter. Treatment-naı¨ve patients (arm A) and Thr790Met-positive patients who progressed on EGFR-TKI therapy (arm B) received osimertinib 80 mg once daily. Dose escalation to 160 mg once daily was performed in cases of intracranial progression without symptomatic systemic progression. The primary endpoint in both arms was
doi:10.1093/annonc/mdz437 | ix177
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz437.052/5638368 by Goteborgs Universitet user on 14 December 2019
with previously reported chemotherapy regimen, CBDCA plus paclitaxel or Cisplatin combination chemotherapy. No treatment-related deaths occurred in this cohort. Grade 3 or worse hematological toxicity was observed in five patients (neutropenia: three patients; anemia: two patients); grade 3 or worse non-hematological toxicity was observed in three patients. None of the patients developed febrile neutropenia. Conclusions: Cisplatin and Irinotecan combination chemotherapy may be a safe and effective first-line chemotherapy regimen for unresectable thymic carcinoma. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: Y. Hosomi: Honoraria (self): AstraZeneca. All other authors have declared no conflicts