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Does progress achieved in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) reach the elderly population?
abstracts
1577P
Analysis of the tumour microenvironment and tumour genotype through different stages of lung adenocarcinoma
P. Zink1, M. Falk1, S. Schatz1, M. Tiemann2 Molecular Pathology, Hematopathology Hamburg, Hamburg, Germany, 2 Hematopathology Hamburg, Hamburg, Germany
1
Background: Treatment options for metastasized NSCLC are steadily evolving and novel therapeutic approaches are increasingly based on molecular data. Predictive biomarkers include the presence of driver mutations and PD-L1 tumor status. The contribution of the tumor microenvironment to patient outcome requires further evaluation. In this study we genetically characterized 133 lung adenocarcinomas, assessed PD-L1 status and quantified tumor-infiltrating lymphocytes (TIL) within the tumor microenvironment. Data was evaluated depending on tumor stage. Methods: Tumor resections of 156 patients with lung adenocarcinomas were categorized into UICC tumor stages I-IV. Immunohistochemical analysis was performed to characterize TIL with antibodies against CD3, CD8, FoxP3 and PD-1 for TLymphocytes, CD19, CD20 (B cells) and CD68 (histiocytes). Total numbers of TIL and tumor cells were analyzed by counting 3 high-power fields each (40x magnification). In addition, we performed amplicon-based next-generation sequencing for 17 therapeutically relevant genes in 133 of cases were material was sufficient. ALK status was assessed by IHC. Results: The most common genetic alterations in our cohort of lung adenocarcinomas were TP53 mutations with 53.38% (71/133), followed by KRAS with 37.59% (50/133). In terms of targetable driver aberrations we detected frequencies of 10.53% for EGFR (14/133), 0.67% (1/133) for BRAF V600E and 3.76% (5/133) for ALK. While driver mutations were evenly distributed through tumor stages I-IV, TP53 mutations were significantly associated with tumor stages III and IV (p ¼ 0.0021). Further, we observed an unexpected correlation of driver alterations (KRAS, BRAF, ALK and EGFR) with the number of infiltrating CD19 positive B cells (p ¼ 0.0151) as well as the number of CD19 and CD20 positive B cell follicles within the tumor environment (p ¼ 0.0334). Conclusions: Supporting the concept of TP53 as a passenger mutation, we detected significantly more TP53 mutations in late stage disease. In addition, we found a pronounced B cell response in tumors carrying driver mutations. Characterization of the tumor microenvironment might become an integral part of biomarker assessment in solid tumors in the future. Legal entity responsible for the study: Hematopathology Hamburg. Funding: Has not received any funding. Disclosure: M. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS. All other authors have declared no conflicts of interest.
1578P
Does progress achieved in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) reach the elderly population?
J. Suipyte1, S. Schmidt2, C. Herrmann3, M. Mousavi3, F. Hitz4, M. Fruh4 Medical Faculty, Oncology & Hematology, University of Zu¨rich, Zurich, Switzerland, 2 Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland, 3Ostschweiz, Krebsliga, St. Gallen, Switzerland, 4Department of Oncology & Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland
1
Background: Although treatment modalities for non-small cell lung cancer (NSCLC) are rapidly evolving, there is insufficient evidence that novel drugs reach elderly patients (aged 70 years) and improve their outcomes. The purpose of this study was to evaluate the access to treatment in the elderly population with stage IV NSCLC in a real life setting and its impact on survival (OS) over the past 10 years. Methods: We compared elderly and younger patients with stage IV NSCLC treated at our tertiary cancer centre and its affiliated smaller hospitals. We collected patients and tumor characteristics such as age at diagnosis, gender, smoking history, histology, molecular subtyping, PDL1 expression status and data on treatment types as well as lines. We grouped the enrolled patients into four same size cohorts based on time and age at diagnosis: patients diagnosed 2005-2007 (elderly cohort-I) and 2015-2016 (elderly cohort-II) were compared to cohorts of patients <70 years old diagnosed during the same time periods (young cohorts-I and -II). The characteristics were analysed using Chi-square Test and survival related endpoints with Kaplan-Meier model. A logrank test was used to test the equality of the survivor functions and a z-Test to assess the differences in survival proportions. Results: 499 NSCLC cases were retrospectively analysed. Median OS significantly improved in both, the elderly and the young cohorts, over time. OS in the elderly cohort-I and -II was slightly lower (3.7 months and 5.3 months) compared to the young cohorts-I and -II (7.8 and 12.1 months). In the young group 12-months OS was significantly improved over the last 10 years (34% [95%CI 27%-42%] and 52% [95%CI 43%61%], p ¼ 0.049). There was no significant improvement in the elderly cohorts (18% [95%CI 11%-25% vs. 31% [95%CI 22%-39%], p ¼ 0.29). Therapy with any line of systemic treatment modalities remained lower in the elderly cohorts as compared to younger patients (53% versus 78%). Conclusions: We observed a significant improvement in OS over the past 10 years in young patients, whereas a similar benefit was not found for the elderly. Our findings highlight a strong need in studying this growing population separately in elderly specific clinical trials. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S. Schmidt: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: TAKEDA; Travel / Accommodation / Expenses: Boehringer Ingelheim. M. Fruh: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda. All other authors have declared no conflicts of interest.
1579P
Prognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)
Y. Ohhara1, T. Kojima2, O. Honjo3, N. Yamada4, T. Sato2, M. Kunisaki5, K. Takamura6, T. Takashina7, N. Sukoh8, H. Tanaka9, Y. Kawai10, Y. Fujita11, F. Sugaya12, F. Hommura13, T. Harada14, H. Ryoichi15, I. Kinoshita1, T. Amano16, S. Oizumi4, H.D. Akita1 1 Department of Medical Oncology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan, 2Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan, 3Department of Respiratory Medicine, Sapporo Minami-Sanjo Hospital, Sapporo, Japan, 4Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan, 5First Department of Medicine, Hokkaido University Hospital, Sapporo, Japan, 6Department of Respiratory Medicine, Obihiro-Kosei General Hospital, Obihiro, Japan, 7Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, Iwamizawa, Japan, 8 Department of Respiratory Medicine, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan, 9Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan, 10Department of Respiratory Medicine, Oji General Hospital, Tomakomai, Japan, 11Department of Respiratory Medicine, National Hospital Organization Asahikiwa Medical Center, Asahikawa, Japan, 12Department of Respiratory Medicine, Teine Keijinkai Hospital, Sapporo, Japan, 13 Department of Respiratory Disease, Sapporo City General Hospital, Sapporo, Japan, 14 Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan, 15 Department of Respiratory Medicine, Asahi General Hospital, Asahi, Japan,16Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan Background: Non-small cell lung cancer (NSCLC) is characterized by a high incidence of brain metastasis (BM) and the prognosis of NSCLC patients with BM is poor. Previous study demonstrated four prognostic factors, which were age, poor PS, presence of extracranial metastases (ECM), and number of BM, in NSCLC patients with BM. This study aimed to identify prognostic factors and clarify the survival in NSCLC patients with BM at the time of a diagnosis.
v650 | NSCLC, Metastatic
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.100/5576210 by guest on 26 October 2019
(institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. J. Spicer: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bayer; Honoraria (institution), Research grant / Funding (institution): BerGenBio ASA; Honoraria (institution), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (institution): BMS; Honoraria (institution), Research grant / Funding (institution): Curis; Honoraria (institution), Research grant / Funding (institution): Genmab; Honoraria (institution), Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution): Starpharma; Honoraria (institution), Research grant / Funding (institution): Taiho; Shareholder / Stockholder / Stock options: IGEM Therapeutics. R.J. Holt: Full / Part-time employment: BerGenBio ASA. J.B. Lorens: Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Full / Part-time employment: BerGenBio ASA. M. Shoaib: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. A. Siddiqui: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. E.V. Schmidt: Full / Part-time employment: Merck Sharp & Dome. M.J. Chisamore: Full / Part-time employment: Merck Sharp & Dome. M.G. Krebs: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Achilles Therapeutics; Advisory / Consultancy: Octimet; Advisory / Consultancy: Janssen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BerGenBio ASA. All other authors have declared no conflicts of interest.
Annals of Oncology
1577P
Analysis of the tumour microenvironment and tumour genotype through different stages of lung adenocarcinoma
P. Zink1, M. Falk1, S. Schatz1, M. Tiemann2 Molecular Pathology, Hematopathology Hamburg, Hamburg, Germany, 2 Hematopathology Hamburg, Hamburg, Germany
1
Background: Treatment options for metastasized NSCLC are steadily evolving and novel therapeutic approaches are increasingly based on molecular data. Predictive biomarkers include the presence of driver mutations and PD-L1 tumor status. The contribution of the tumor microenvironment to patient outcome requires further evaluation. In this study we genetically characterized 133 lung adenocarcinomas, assessed PD-L1 status and quantified tumor-infiltrating lymphocytes (TIL) within the tumor microenvironment. Data was evaluated depending on tumor stage. Methods: Tumor resections of 156 patients with lung adenocarcinomas were categorized into UICC tumor stages I-IV. Immunohistochemical analysis was performed to characterize TIL with antibodies against CD3, CD8, FoxP3 and PD-1 for TLymphocytes, CD19, CD20 (B cells) and CD68 (histiocytes). Total numbers of TIL and tumor cells were analyzed by counting 3 high-power fields each (40x magnification). In addition, we performed amplicon-based next-generation sequencing for 17 therapeutically relevant genes in 133 of cases were material was sufficient. ALK status was assessed by IHC. Results: The most common genetic alterations in our cohort of lung adenocarcinomas were TP53 mutations with 53.38% (71/133), followed by KRAS with 37.59% (50/133). In terms of targetable driver aberrations we detected frequencies of 10.53% for EGFR (14/133), 0.67% (1/133) for BRAF V600E and 3.76% (5/133) for ALK. While driver mutations were evenly distributed through tumor stages I-IV, TP53 mutations were significantly associated with tumor stages III and IV (p ¼ 0.0021). Further, we observed an unexpected correlation of driver alterations (KRAS, BRAF, ALK and EGFR) with the number of infiltrating CD19 positive B cells (p ¼ 0.0151) as well as the number of CD19 and CD20 positive B cell follicles within the tumor environment (p ¼ 0.0334). Conclusions: Supporting the concept of TP53 as a passenger mutation, we detected significantly more TP53 mutations in late stage disease. In addition, we found a pronounced B cell response in tumors carrying driver mutations. Characterization of the tumor microenvironment might become an integral part of biomarker assessment in solid tumors in the future. Legal entity responsible for the study: Hematopathology Hamburg. Funding: Has not received any funding. Disclosure: M. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS. All other authors have declared no conflicts of interest.
1578P
Does progress achieved in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) reach the elderly population?
J. Suipyte1, S. Schmidt2, C. Herrmann3, M. Mousavi3, F. Hitz4, M. Fruh4 Medical Faculty, Oncology & Hematology, University of Zu¨rich, Zurich, Switzerland, 2 Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland, 3Ostschweiz, Krebsliga, St. Gallen, Switzerland, 4Department of Oncology & Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland
1
Background: Although treatment modalities for non-small cell lung cancer (NSCLC) are rapidly evolving, there is insufficient evidence that novel drugs reach elderly patients (aged 70 years) and improve their outcomes. The purpose of this study was to evaluate the access to treatment in the elderly population with stage IV NSCLC in a real life setting and its impact on survival (OS) over the past 10 years. Methods: We compared elderly and younger patients with stage IV NSCLC treated at our tertiary cancer centre and its affiliated smaller hospitals. We collected patients and tumor characteristics such as age at diagnosis, gender, smoking history, histology, molecular subtyping, PDL1 expression status and data on treatment types as well as lines. We grouped the enrolled patients into four same size cohorts based on time and age at diagnosis: patients diagnosed 2005-2007 (elderly cohort-I) and 2015-2016 (elderly cohort-II) were compared to cohorts of patients <70 years old diagnosed during the same time periods (young cohorts-I and -II). The characteristics were analysed using Chi-square Test and survival related endpoints with Kaplan-Meier model. A logrank test was used to test the equality of the survivor functions and a z-Test to assess the differences in survival proportions. Results: 499 NSCLC cases were retrospectively analysed. Median OS significantly improved in both, the elderly and the young cohorts, over time. OS in the elderly cohort-I and -II was slightly lower (3.7 months and 5.3 months) compared to the young cohorts-I and -II (7.8 and 12.1 months). In the young group 12-months OS was significantly improved over the last 10 years (34% [95%CI 27%-42%] and 52% [95%CI 43%61%], p ¼ 0.049). There was no significant improvement in the elderly cohorts (18% [95%CI 11%-25% vs. 31% [95%CI 22%-39%], p ¼ 0.29). Therapy with any line of systemic treatment modalities remained lower in the elderly cohorts as compared to younger patients (53% versus 78%). Conclusions: We observed a significant improvement in OS over the past 10 years in young patients, whereas a similar benefit was not found for the elderly. Our findings highlight a strong need in studying this growing population separately in elderly specific clinical trials. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S. Schmidt: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: TAKEDA; Travel / Accommodation / Expenses: Boehringer Ingelheim. M. Fruh: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda. All other authors have declared no conflicts of interest.
1579P
Prognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)
Y. Ohhara1, T. Kojima2, O. Honjo3, N. Yamada4, T. Sato2, M. Kunisaki5, K. Takamura6, T. Takashina7, N. Sukoh8, H. Tanaka9, Y. Kawai10, Y. Fujita11, F. Sugaya12, F. Hommura13, T. Harada14, H. Ryoichi15, I. Kinoshita1, T. Amano16, S. Oizumi4, H.D. Akita1 1 Department of Medical Oncology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan, 2Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan, 3Department of Respiratory Medicine, Sapporo Minami-Sanjo Hospital, Sapporo, Japan, 4Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan, 5First Department of Medicine, Hokkaido University Hospital, Sapporo, Japan, 6Department of Respiratory Medicine, Obihiro-Kosei General Hospital, Obihiro, Japan, 7Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, Iwamizawa, Japan, 8 Department of Respiratory Medicine, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan, 9Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan, 10Department of Respiratory Medicine, Oji General Hospital, Tomakomai, Japan, 11Department of Respiratory Medicine, National Hospital Organization Asahikiwa Medical Center, Asahikawa, Japan, 12Department of Respiratory Medicine, Teine Keijinkai Hospital, Sapporo, Japan, 13 Department of Respiratory Disease, Sapporo City General Hospital, Sapporo, Japan, 14 Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan, 15 Department of Respiratory Medicine, Asahi General Hospital, Asahi, Japan,16Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan Background: Non-small cell lung cancer (NSCLC) is characterized by a high incidence of brain metastasis (BM) and the prognosis of NSCLC patients with BM is poor. Previous study demonstrated four prognostic factors, which were age, poor PS, presence of extracranial metastases (ECM), and number of BM, in NSCLC patients with BM. This study aimed to identify prognostic factors and clarify the survival in NSCLC patients with BM at the time of a diagnosis.
v650 | NSCLC, Metastatic
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.100/5576210 by guest on 26 October 2019
(institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. J. Spicer: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bayer; Honoraria (institution), Research grant / Funding (institution): BerGenBio ASA; Honoraria (institution), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (institution): BMS; Honoraria (institution), Research grant / Funding (institution): Curis; Honoraria (institution), Research grant / Funding (institution): Genmab; Honoraria (institution), Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution): Starpharma; Honoraria (institution), Research grant / Funding (institution): Taiho; Shareholder / Stockholder / Stock options: IGEM Therapeutics. R.J. Holt: Full / Part-time employment: BerGenBio ASA. J.B. Lorens: Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Full / Part-time employment: BerGenBio ASA. M. Shoaib: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. A. Siddiqui: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. E.V. Schmidt: Full / Part-time employment: Merck Sharp & Dome. M.J. Chisamore: Full / Part-time employment: Merck Sharp & Dome. M.G. Krebs: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Achilles Therapeutics; Advisory / Consultancy: Octimet; Advisory / Consultancy: Janssen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BerGenBio ASA. All other authors have declared no conflicts of interest.
Annals of Oncology