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Immuno-oncology biomarker study in non-small cell lung cancer harboring oncogenic driver alterations: LC-SCRUM-IBIS
abstracts
Annals of Oncology
MO3 7 3½Encore
Immuno-oncology biomarker study in non-small cell lung cancer harboring oncogenic driver alterations: LC-SCRUM-IBIS
Masahiro Kodani1, Kiyotaka Yoh2, Shingo Matsumoto2, Kei Kunimasa3, Koichi Nishi4, Taku Nakagawa5, Shunichi Sugawara6, Tomohiro Kato7, Jun Sakakibara-Konishi8, Koji Tsuta9, Yuichiro Hayashi10, Noriko Motoi11, Genichiro Ishii12, Koichi Goto2 1 Tottori University, 2National Cancer Center Hospital East, 3Osaka International Cancer Institute, 4Ishikawa Prefecutual Central Hospital, 5Omagari Kosei Medical Center, 6 Sendai Kousei Hospital, 7National Hospital Organization Himeji Medical Center, 8 Hokkaido University Hospital, 9Kansai Medical University, 10Keio University School of Medicine, 11National Cancer Center Hospital, 12Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Background: The efficacy of immune checkpoint inhibitors (ICI) and PD-L1 status in patients with advanced non-small cell lung cancer (NSCLC) harboring oncogenic alterations has not been fully investigated. We initiated this immuno-oncology biomarker study as part of nationwide genomic screening by LC-SCRUM-Japan (LC-SCRUMIBIS). Methods: Lung cancer patients enrolled in LC-SCRUM-IBIS underwent targeted NGS with Oncomine Comprehensive Assay, PD-L1 IHC assays and further wholeexome sequencing (WES) to determine tumor mutation burden. According to subtype of oncogenic alterations, the efficacy of ICI and PD-L1 status were analyzed. Results: Between Feb 2017 and May 2018, 1017 lung cancer patients were enrolled. Of these, 832 NSCLC patients were included in this analysis. Targeted NGS showed that major oncogenic alterations included 157 EGFR, 83 KRAS, 33 MET, 28 HER2, 27 FGFR, 22 PIK3CA, 19 ALK, 15 ROS1, 10 RET, 5 BRAF and others. High expression of PD-L1 (> 50% of tumor cells by 22C3) were observed in RET (70%), MET (67%), ROS1 (53%), KRAS (41%) and BRAF (40%) positive tumors. 105 patients were evaluable for the efficacy of ICI. Among them, 104 were treated with PD-1/PD-L1 monotherapy and only 1 in combination therapy of ICI. Median treatment line was 2 (range, 1-9). The response rate was 19% (20/105) and median progression-free survival (PFS) and overall survival (OS) were 3.3 and 18.3 months. In 50 patients harboring at least one oncogenic alterations, the response rate, PFS and OS were 18% (9/50), 3.3 and 24.8 months. Among 9 responders to ICI, 3 had KRAS, 2 had MET and 1 each had ALK/EGFR/HER2/RET. Six (26%) of 23 patients with both high PD-L1 expression and at least one oncogenic alterations responded to ICI. Conclusions: PD-L1 status seemed to vary among patients with advanced NSCLC harboring oncogenic alterations. New biomarker for ICI therapy in this population should be moreover explored. Updated results on WES analysis will be presented at the meeting.
MO3 7 4
Real-World Effectiveness of Nivolumab by PD-L1 Expression in NSCLC pts in Japan: A Multicenter-Retrospective Study
Young Hak Kim1,2, Ryo Morita2, Kyoichi Okishio2, Junichi Simizu2, Haruhiro Saito2, Hiroshi Sakai2, Osamu Hataji2, Makiko Yomota2, Makoto Nishio2, Keisuke Aoe2, Osamu Kanai2, Toru Kumagai2, Kayoko Kibata2, Hiroaki Tsukamoto2, Satoshi Oizumi2, Keisuke Tomii2, Hiroshi Tanaka2, Keiko Mizuno2, Hirotoshi Hoshiyama3, Kenya Ochi4, Yuichiro Ohe2 1 Department of Respiratory Medicine, Kyoto University Hospital, 2Nivolumab Japan Real World Study Group, 3Bristol-Myers Squibb K.K, 4Ono Pharmaceutical Co., Ltd Background: Since its approval in December 2015, nivolumab has been widely used as a second-line treatment for non-small cell lung cancer (NSCLC) patients regardless of tumor PD-L1 expression or histology. However, the relationship between nivolumab effectiveness and PD-L1 expression using 22C3 PharmDx in the real-world setting is unclear. Methods: Data from patient who initiated nivolumab treatment from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan. Tumor PD-L1 expression was determined using PD-L1 IHC 22C3 PharmDx or 28-8 PharmDx assays. Here, we report the relationship between nivolumab effectiveness/ safety and PD-L1 expression using 22C3 PharmDx, from a multicenter, observational study; CA209-9CR (NCT03273790). Results: PD-L1 expression in 348 cases of NSCLC was determined using the 22C3 PharmDx assay. The propotion of cases with PD-L1 negative (<1%), low (1-49%), and high (50%) expression were 47.1%, 31.3% and 21.6%, respectively. The ORR of Nivolumab in squamous NSCLC pts with PD-L1 negative, low, high expression were
Volume 30 | Supplement 6 | October 2019
8.8%, 23.1%, and 28.6%, respectively. The ORR of Nivolumab in adenocarsinoma NSCLC pts with PD-L1 negative, low, high expression were 12.7%, 20.3%, and 41.7%, respectively. Among 182 pts with PD-L1 expression that was measured both with 22C3 PharmDx and 28-8 PharmDx assay, concordance of the two assays showed 77.5%. Relationship between PD-L1 expression and PFS, OS and safety will also be presented at the meeting. Conclusion: These real-world data show relationship of nivolumab effectiveness and PD-L1 expression using 22C3 PharmDx.
MO3 7 6
Exploratory Analysis of Nivolumab Effectiveness with Lab Data in NSCLC pts in Japan: A Multicenter-Retrospective Study
Keisuke Aoe1,2, Ryo Morita2, Kyoichi Okishio2, Junichi Shimizu2, Haruhiro Saito2, Hiroshi Sakai2, Yong Hak Kim2, Osamu Hataji2, Makiko Yomota2, Makoto Nishio2, Osamu Kanai2, Toru Kumagai2, Kayoko Kibata2, Hiroaki Tsukamoto2, Satoshi Oizumi2, Keisuke Tomii2, Hiroshi Tanaka2, Keiko Mizuno2, Hirotoshi Hoshiyama3, Kenya Ochi4, Yuichiro Ohe2 1 National Hospital Organization Yamaguchi, Ube Medical Center, 2Nivolumab Japan Real World Study Group, 3Bristol-Myers Squibb K.K, 4Ono Pharmaceutical Co., Ltd Background: In December 2015, nivolumab was approved for previously treated advanced NSCLC irrespective of PD-L1 expression or histology in Japan. Real-world data can provide insights beyond the clinical trial, and in this analysis we study a large Japanese patient cohort. Methods: Data for 901 patients who initiated nivolumab treatment for advanced NSCLC from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan, including clinical laboratory data before and all the available data during nivolumab treatment. Here we report an exploratory analysis on the association of nivolumab effectiveness with the clinical laboratory data of the Japanese advanced NSCLC patients from a multicenter, observational study; CA209-9CR (NCT03273790). Results: Analysis on association of objective response rate (ORR) with each clinical laboratory data at baseline among responders and non-responders suggested that neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), albumin, sodium, CYFRA, and uric acid at baseline were associated with significantly improved ORR. Further analyses on those multiple factors are planned to identify associations with improved outcome of with nivolumab treatment beyond ORR.
MO3 8 2
Characteristics and prognosis of leptomeningeal metastasis in patients with breast cancer
Yurina Maeshima1, Yoshinori Ito2, Tomoko Shibayama2, Mari Hosonaga2, Makiko Ono3, Kokoro Kobayashi2, Takayuki Kobayashi2, Takayuki Ueno1, Masahiko Oguchi4, Syunji Takahashi3, Shinji Ohno4 1 Department of Breast Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 2Department of Breast Medical Oncology,The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 4Department of Radiation Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Background: The incidence of leptomeningeal metastasis (LM) in breast cancer is reported to be approximately 5% and prognosis of breast cancer patients with LM is poor. Characteristics and treatment for breast cancer with LM remain unclear. The objective of this study is to observe outcome of breast cancer patients with LM in the current background. Patients and methods: We retrospectively reviewed 84 breast cancer patients who were diagnosed with LM and received treatment for LM between 2005 and 2018 in our institution. LM was diagnosed by brain imaging and/or lumbar puncture with the presence of malignant cells in cerebrospinal fluid. Results: Median age at diagnosis of LM was 56.5 years (33-76). Thirty-nine (46%), 7 (8%), 12 (14%), and 24 (29%) were HRþ/HER2-, HRþ/HER2þ, HR-/HER2þ and triple negative, respectively. Median time to LM from the diagnosis of distant metastasis was 66.6 months, and significantly longer in HRþ/HER2þ compared with other subtypes (p < 0.0045). Twenty-four (29%) women had developed brain metastasis at diagnosis of LM. Of 84 patients, 72 patients (85.7%), 4 (4.8%), and 8 (9.5%) were treated with radiotherapy (RT), IT, and RTþIT, respectively. Median overall survival (OS) was 3.8 months, with 11 patients (13%) surviving longer than 1 year. In univariate and multivariate analysis, higher performance status (PS), and RT with planned dose were positive prognostic factors for OS (p ¼ 0.027 and p < 0.001). Median survival of RTþIT patients was 11.9 months, 1.7months for IT and 3.7 months for RT patients (p ¼ 0.132). Six months survival rate following LM were 26.7% for RT, 0% for IT and 53.6% for RTþIT respectively. Age, HR, and HER2 status, breast cancer subtype, cranial only involvement and neurological findings were not associated with OS. Conclusion: Survival following a diagnosis of LM in breast cancer patients remains poor, but some patients survived more than 1 year in this study. PS and RT with planned dose were independent prognostic factors.
doi:10.1093/annonc/mdz338 | vi113
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz338.098/5583137 by guest on 24 October 2019
expression, with an adjusted odds ratio of 3.2 (95% confidence Interval [CI], 1.1 to 9.0). Among 70 pts with 22C3-PD-L1 TPS of 1% or higher tumors, 14 pts were evaluable for the efficacy of pembrolizumab treatment. Of these 14 pts, only two pts with UC were TKI naı¨ve. Objective response was observed in 36% (95% CI, 16 to 61) of all 14 pts, 22% (95% CI, 6 to 55) of nine pts with CM, and 60% (95% CI, 23 to 88) of five pts with UC. Of nine pts with 22C3-PD-L1 TPS of 50% or higher tumors, five pts including two TKI naı¨ve pts had an objective response (56%; 95% CI, 27 to 81), while none of five pts with 22C3-PD-L1 TPS 1 to 49% tumors had an objective response. Conclusions: PD-L1 Expression was significantly associated with subtype of EGFR mutation in Japanese pts with EGFR-Mutant NSCLC. 22C3-PD-L1 TPS of 50% or higher may be a predictive marker of pembrolizumab treatment for EGFR-Mutant NSCLC.
Annals of Oncology
MO3 7 3½Encore
Immuno-oncology biomarker study in non-small cell lung cancer harboring oncogenic driver alterations: LC-SCRUM-IBIS
Masahiro Kodani1, Kiyotaka Yoh2, Shingo Matsumoto2, Kei Kunimasa3, Koichi Nishi4, Taku Nakagawa5, Shunichi Sugawara6, Tomohiro Kato7, Jun Sakakibara-Konishi8, Koji Tsuta9, Yuichiro Hayashi10, Noriko Motoi11, Genichiro Ishii12, Koichi Goto2 1 Tottori University, 2National Cancer Center Hospital East, 3Osaka International Cancer Institute, 4Ishikawa Prefecutual Central Hospital, 5Omagari Kosei Medical Center, 6 Sendai Kousei Hospital, 7National Hospital Organization Himeji Medical Center, 8 Hokkaido University Hospital, 9Kansai Medical University, 10Keio University School of Medicine, 11National Cancer Center Hospital, 12Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Background: The efficacy of immune checkpoint inhibitors (ICI) and PD-L1 status in patients with advanced non-small cell lung cancer (NSCLC) harboring oncogenic alterations has not been fully investigated. We initiated this immuno-oncology biomarker study as part of nationwide genomic screening by LC-SCRUM-Japan (LC-SCRUMIBIS). Methods: Lung cancer patients enrolled in LC-SCRUM-IBIS underwent targeted NGS with Oncomine Comprehensive Assay, PD-L1 IHC assays and further wholeexome sequencing (WES) to determine tumor mutation burden. According to subtype of oncogenic alterations, the efficacy of ICI and PD-L1 status were analyzed. Results: Between Feb 2017 and May 2018, 1017 lung cancer patients were enrolled. Of these, 832 NSCLC patients were included in this analysis. Targeted NGS showed that major oncogenic alterations included 157 EGFR, 83 KRAS, 33 MET, 28 HER2, 27 FGFR, 22 PIK3CA, 19 ALK, 15 ROS1, 10 RET, 5 BRAF and others. High expression of PD-L1 (> 50% of tumor cells by 22C3) were observed in RET (70%), MET (67%), ROS1 (53%), KRAS (41%) and BRAF (40%) positive tumors. 105 patients were evaluable for the efficacy of ICI. Among them, 104 were treated with PD-1/PD-L1 monotherapy and only 1 in combination therapy of ICI. Median treatment line was 2 (range, 1-9). The response rate was 19% (20/105) and median progression-free survival (PFS) and overall survival (OS) were 3.3 and 18.3 months. In 50 patients harboring at least one oncogenic alterations, the response rate, PFS and OS were 18% (9/50), 3.3 and 24.8 months. Among 9 responders to ICI, 3 had KRAS, 2 had MET and 1 each had ALK/EGFR/HER2/RET. Six (26%) of 23 patients with both high PD-L1 expression and at least one oncogenic alterations responded to ICI. Conclusions: PD-L1 status seemed to vary among patients with advanced NSCLC harboring oncogenic alterations. New biomarker for ICI therapy in this population should be moreover explored. Updated results on WES analysis will be presented at the meeting.
MO3 7 4
Real-World Effectiveness of Nivolumab by PD-L1 Expression in NSCLC pts in Japan: A Multicenter-Retrospective Study
Young Hak Kim1,2, Ryo Morita2, Kyoichi Okishio2, Junichi Simizu2, Haruhiro Saito2, Hiroshi Sakai2, Osamu Hataji2, Makiko Yomota2, Makoto Nishio2, Keisuke Aoe2, Osamu Kanai2, Toru Kumagai2, Kayoko Kibata2, Hiroaki Tsukamoto2, Satoshi Oizumi2, Keisuke Tomii2, Hiroshi Tanaka2, Keiko Mizuno2, Hirotoshi Hoshiyama3, Kenya Ochi4, Yuichiro Ohe2 1 Department of Respiratory Medicine, Kyoto University Hospital, 2Nivolumab Japan Real World Study Group, 3Bristol-Myers Squibb K.K, 4Ono Pharmaceutical Co., Ltd Background: Since its approval in December 2015, nivolumab has been widely used as a second-line treatment for non-small cell lung cancer (NSCLC) patients regardless of tumor PD-L1 expression or histology. However, the relationship between nivolumab effectiveness and PD-L1 expression using 22C3 PharmDx in the real-world setting is unclear. Methods: Data from patient who initiated nivolumab treatment from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan. Tumor PD-L1 expression was determined using PD-L1 IHC 22C3 PharmDx or 28-8 PharmDx assays. Here, we report the relationship between nivolumab effectiveness/ safety and PD-L1 expression using 22C3 PharmDx, from a multicenter, observational study; CA209-9CR (NCT03273790). Results: PD-L1 expression in 348 cases of NSCLC was determined using the 22C3 PharmDx assay. The propotion of cases with PD-L1 negative (<1%), low (1-49%), and high (50%) expression were 47.1%, 31.3% and 21.6%, respectively. The ORR of Nivolumab in squamous NSCLC pts with PD-L1 negative, low, high expression were
Volume 30 | Supplement 6 | October 2019
8.8%, 23.1%, and 28.6%, respectively. The ORR of Nivolumab in adenocarsinoma NSCLC pts with PD-L1 negative, low, high expression were 12.7%, 20.3%, and 41.7%, respectively. Among 182 pts with PD-L1 expression that was measured both with 22C3 PharmDx and 28-8 PharmDx assay, concordance of the two assays showed 77.5%. Relationship between PD-L1 expression and PFS, OS and safety will also be presented at the meeting. Conclusion: These real-world data show relationship of nivolumab effectiveness and PD-L1 expression using 22C3 PharmDx.
MO3 7 6
Exploratory Analysis of Nivolumab Effectiveness with Lab Data in NSCLC pts in Japan: A Multicenter-Retrospective Study
Keisuke Aoe1,2, Ryo Morita2, Kyoichi Okishio2, Junichi Shimizu2, Haruhiro Saito2, Hiroshi Sakai2, Yong Hak Kim2, Osamu Hataji2, Makiko Yomota2, Makoto Nishio2, Osamu Kanai2, Toru Kumagai2, Kayoko Kibata2, Hiroaki Tsukamoto2, Satoshi Oizumi2, Keisuke Tomii2, Hiroshi Tanaka2, Keiko Mizuno2, Hirotoshi Hoshiyama3, Kenya Ochi4, Yuichiro Ohe2 1 National Hospital Organization Yamaguchi, Ube Medical Center, 2Nivolumab Japan Real World Study Group, 3Bristol-Myers Squibb K.K, 4Ono Pharmaceutical Co., Ltd Background: In December 2015, nivolumab was approved for previously treated advanced NSCLC irrespective of PD-L1 expression or histology in Japan. Real-world data can provide insights beyond the clinical trial, and in this analysis we study a large Japanese patient cohort. Methods: Data for 901 patients who initiated nivolumab treatment for advanced NSCLC from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan, including clinical laboratory data before and all the available data during nivolumab treatment. Here we report an exploratory analysis on the association of nivolumab effectiveness with the clinical laboratory data of the Japanese advanced NSCLC patients from a multicenter, observational study; CA209-9CR (NCT03273790). Results: Analysis on association of objective response rate (ORR) with each clinical laboratory data at baseline among responders and non-responders suggested that neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), albumin, sodium, CYFRA, and uric acid at baseline were associated with significantly improved ORR. Further analyses on those multiple factors are planned to identify associations with improved outcome of with nivolumab treatment beyond ORR.
MO3 8 2
Characteristics and prognosis of leptomeningeal metastasis in patients with breast cancer
Yurina Maeshima1, Yoshinori Ito2, Tomoko Shibayama2, Mari Hosonaga2, Makiko Ono3, Kokoro Kobayashi2, Takayuki Kobayashi2, Takayuki Ueno1, Masahiko Oguchi4, Syunji Takahashi3, Shinji Ohno4 1 Department of Breast Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 2Department of Breast Medical Oncology,The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 4Department of Radiation Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Background: The incidence of leptomeningeal metastasis (LM) in breast cancer is reported to be approximately 5% and prognosis of breast cancer patients with LM is poor. Characteristics and treatment for breast cancer with LM remain unclear. The objective of this study is to observe outcome of breast cancer patients with LM in the current background. Patients and methods: We retrospectively reviewed 84 breast cancer patients who were diagnosed with LM and received treatment for LM between 2005 and 2018 in our institution. LM was diagnosed by brain imaging and/or lumbar puncture with the presence of malignant cells in cerebrospinal fluid. Results: Median age at diagnosis of LM was 56.5 years (33-76). Thirty-nine (46%), 7 (8%), 12 (14%), and 24 (29%) were HRþ/HER2-, HRþ/HER2þ, HR-/HER2þ and triple negative, respectively. Median time to LM from the diagnosis of distant metastasis was 66.6 months, and significantly longer in HRþ/HER2þ compared with other subtypes (p < 0.0045). Twenty-four (29%) women had developed brain metastasis at diagnosis of LM. Of 84 patients, 72 patients (85.7%), 4 (4.8%), and 8 (9.5%) were treated with radiotherapy (RT), IT, and RTþIT, respectively. Median overall survival (OS) was 3.8 months, with 11 patients (13%) surviving longer than 1 year. In univariate and multivariate analysis, higher performance status (PS), and RT with planned dose were positive prognostic factors for OS (p ¼ 0.027 and p < 0.001). Median survival of RTþIT patients was 11.9 months, 1.7months for IT and 3.7 months for RT patients (p ¼ 0.132). Six months survival rate following LM were 26.7% for RT, 0% for IT and 53.6% for RTþIT respectively. Age, HR, and HER2 status, breast cancer subtype, cranial only involvement and neurological findings were not associated with OS. Conclusion: Survival following a diagnosis of LM in breast cancer patients remains poor, but some patients survived more than 1 year in this study. PS and RT with planned dose were independent prognostic factors.
doi:10.1093/annonc/mdz338 | vi113
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz338.098/5583137 by guest on 24 October 2019
expression, with an adjusted odds ratio of 3.2 (95% confidence Interval [CI], 1.1 to 9.0). Among 70 pts with 22C3-PD-L1 TPS of 1% or higher tumors, 14 pts were evaluable for the efficacy of pembrolizumab treatment. Of these 14 pts, only two pts with UC were TKI naı¨ve. Objective response was observed in 36% (95% CI, 16 to 61) of all 14 pts, 22% (95% CI, 6 to 55) of nine pts with CM, and 60% (95% CI, 23 to 88) of five pts with UC. Of nine pts with 22C3-PD-L1 TPS of 50% or higher tumors, five pts including two TKI naı¨ve pts had an objective response (56%; 95% CI, 27 to 81), while none of five pts with 22C3-PD-L1 TPS 1 to 49% tumors had an objective response. Conclusions: PD-L1 Expression was significantly associated with subtype of EGFR mutation in Japanese pts with EGFR-Mutant NSCLC. 22C3-PD-L1 TPS of 50% or higher may be a predictive marker of pembrolizumab treatment for EGFR-Mutant NSCLC.