Browsing Over 3689 Presentations
The optimal sequence: Does overall survival matter? (ID 265)
- Tony S.K. Mok (Shatin, Hong Kong PRC)
1221P - Anti-PD-L1/IL-15 fusion protein generates robust adaptive immune gene signatures in tumours leading to tumour inhibition and memory responses (ID 5717)
- Stella Martomo (New York City, United States of America)
Abstract
Background
We have generated a therapeutic anti-PD-L1/IL-15 fusion protein (KD033) by combining a proprietary, fully human, high affinity anti-PD-L1 antibody with human IL-15. We have also generated a surrogate KD033 by combining an anti-mouse PD-L1 surrogate antibody with human IL-15. Both KD033 and KD033 surrogate significantly increased CD8+ T, NK and NKT cells in peripheral blood in monkeys and mice respectively. KD033 surrogate treatment resulted in tumor clearance and generated memory responses in syngeneic mouse models of colon carcinoma. We examined the extent of memory responses in these KD033 surrogate-treated tumor-free mice and evaluated the molecular mechanisms of KD033 surrogate efficacy.
Methods
Mouse CT26 colon carcinoma cells were grown subcutaneously in Balb/c mice prior to intravenous treatments with fusion proteins. Tumor-free mice were re-challenged with tumors from the same genetic background. For immune gene expression analysis, tumors were isolated 7 days after treatments and analyzed using the mouse PanCancer IO 360 Gene Expression Panel from Nanostring.
Results
KD033 surrogate treatment was associated with increased cytotoxic lymphocyte infiltrations in tumors and the microenvironment. One hundred percent (100%) of KD033 surrogate-treated tumor-free animals rejected the same tumor without any additional treatments. Mice re-challenged with unrelated tumors from the same background were rejected or demonstrated reduction of tumor growth without further treatments. KD033 surrogate-treated tumors showed significant increases in expression of genes involved in cytokine, adaptive and inflammatory pathways and upregulation of immune gene signatures involving not only cytotoxic cells but also dendritic and B cells.
Conclusions
KD033 surrogate inhibited tumor growth inhibition and demonstrated evidence of epitope spreading. Broad activation of innate and adaptive immune responses in tumors was observed. These observations strongly support KD033 clinical development. A phase I clinical trial of KD033 is planned in 2H 2019.
Legal entity responsible for the study
Animal studies were conducted for Kadmon by Crown Bioscience Inc. with approved SOP and IACUC protocol. Nanostring platform analysis was done for Kadmon by Canopy Biosciences.
Funding
Kadmon Corporation, LLC.
Disclosure
S. Martomo: Full / Part-time employment: Kadmon Corporation. X. Feng: Full / Part-time employment: Kadmon Corporation. D. Lu: Full / Part-time employment: Kadmon Corporation. Z. Polonskaya: Full / Part-time employment: Kadmon Corporation. X. Luna: Full / Part-time employment: Kadmon Corporation. M.V. Poyurovsky: Full / Part-time employment: Kadmon Corporation. K. McCracken: Full / Part-time employment: Kadmon Corporation. F. Miyara: Full / Part-time employment: Kadmon Corporation. L. Li: Full / Part-time employment: Kadmon Corporation. S. Aggarwal: Full / Part-time employment: Kadmon Corporation. J. Patel: Full / Part-time employment: Kadmon Corporation.
LBA56 - Primary efficacy analysis results from the SORCE trial (RE05): Adjuvant sorafenib for renal cell carcinoma at intermediate or high risk of relapse: An international, randomised double-blind phase III trial led by the MRC CTU at UCL (ID 2483)
- Tim Q. Eisen (Cambridge, Cambridgeshire, United Kingdom)
Abstract
Background
SORCE is a randomised, double-blind trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) at intermediate or high risk of recurrence (Leibovich classification).
Methods
We recruited patients from 147 sites in the UK, Australia, France, Belgium, Denmark, The Netherlands and Spain and randomised them (2:3:3) between three years of placebo (A), one year of sorafenib followed by two years of placebo (B) and three years of sorafenib (C). The initial sorafenib dose was 400mg twice per day orally, amended during trial recruitment to a reduced starting dose of 400mg daily. The primary outcome is investigator-reported disease-free survival (DFS). Given the results of the ASSURE and S-TRAC trials, and blinded to SORCE outcomes, we revised the primary analysis to compare three years of sorafenib (arm C) vs placebo (arm A) to focus on the question of longer exposure to sorafenib.
Results
Between July 2007 and April 2013, we randomised 1711 patients; 430, 642, and 639 to arms A, B, and C respectively. Median age was 58 years; 71% male, 84% clear cell histology, 53% at intermediate risk of recurrence and 47% at high risk of recurrence. We observed no differences in DFS or OS in any of our pre-planned and pre-powered analyses: all randomised patients, high-risk patients only, and patients with clear cell RCC only. Median DFS was not reached for three years sorafenib or for placebo (HR 1.01, 95% CI 0.83 -1.23, p=0.95). We observed non-proportional hazards: restricted mean survival time (RMST) was 6.81 years for three years of sorafenib and 6.82 years for placebo, RMST difference 0.01, 95% CI -0.49 – 0.48, p=0.99. Despite offering treatment adaptations, over half of patients stopped treatment early. Grade 3 hand-foot syndrome was reported in 24% of patients on sorafenib.
Conclusions
Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence following nephrectomy; it is the appropriate control of our current international adjuvant RCC trial, RAMPART.
Clinical trial identification
ISRCTN38934710; EudraCT: 2006-006079-19; NCT00492258.
Legal entity responsible for the study
University College London (UCL).
Funding
Cancer Research UK, UK Medical Research Council, Educational Grants and Drug Supply from Bayer, Cancer Australia Support for Cancer Clinical Trials Program and University College London.
Disclosure
T.Q.G. Eisen: Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Research grant / Funding (self): Pfizer; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): GSK; Honoraria (self): AVEO; Honoraria (self): Astellas; Honoraria (self): Boehringer Ingelheim. I.D. Davis: Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche / Genentech; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bristol-Myers Squibb. M.R. Stockler: Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Binomics; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Tilray. J.M.G. Larkin: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Achilles Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Covance; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Aveo; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: Eisai; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Imugene; Advisory / Consultancy: Incyte; Advisory / Consultancy: iOnctura. A. Bex: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy, Non-remunerated activity/ies: BMS; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Non-remunerated activity/ies: Roche. S. Joniau: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas ; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ferring; Speaker Bureau / Expert testimony: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MDX Health; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: Sanofi. J. Bellmunt: Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Takeda; Shareholder / Stockholder / Stock options: Biocline. All other authors have declared no conflicts of interest.
1494P - Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study (ID 4305)
- Fabrice Barlesi (Marseille, CEDEX 20, France)
Abstract
Background
The EVIDENS study aims to describe clinical characteristics and health-related quality of life (HRQoL) of lung cancer patients treated with nivolumab in real-life in France and to assess its effectiveness and safety.
Methods
EVIDENS is an observational, multicenter, longitudinal cohort study of adult lung cancer patients treated with nivolumab. Survival was assessed using the Kaplan-Meier method and health-related quality of life (HRQoL) was assessed using EQ-5D-3L questionnaire.
Results
A total of 1,462 lung cancer patients were enrolled in the study from Oct 2016 to Nov 2017 in 146 French centers. Previous reports with a 8-month minimum follow-up showed that baseline patient and tumor characteristics from EVIDENS were representative of a standard advanced NSCLC population and that nivolumab was mostly administered as a 2nd line regimen. Median PFS and median OS was 2.8 months (95% CI: 2.6-3.0) and 10 months (95% CI: 9.2-11.0), respectively. Adverse events occurred in 440 patients (31.6%), including 98 patients (7.0%) with grade 3-4 events. Concerning HRQoL, mean change of visual analog score from baseline was statistically significant at 9 and 12 months and minimal important difference was achieved at 12 months for the squamous population. The analysis presented during the congress will include updated effectiveness, safety and HRQoL data as well as subgroups of interest (e.g. brain metastasis, age, prior radiotherapy) with a 17-month minimum follow-up.
Conclusions
TTo date, EVIDENS is the largest prospective observational study of nivolumab in lung cancer patients confirming effectiveness and safety in the real world setting. This updated analysis provides new insights on the experience of nivolumab over a period of longer follow-up and, for the first time, in clinically important subgroups of interest.
Clinical trial identification
NCT03382496.
Legal entity responsible for the study
Bristol-Myers Squibb France.
Funding
Bristol-Myers Squibb France.
Disclosure
A. Dixmier: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Lilly. D. Debieuvre: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugaï; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): GSK; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Mundipharma. J.B. Auliac: Advisory / Consultancy, Non-remunerated activity/ies: Bristol-Myers Squibb; Advisory / Consultancy: Roche. N. Benoit: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca. D. Moro-Sibilot: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Takeda. C. Audigier-Valette: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (institution), Advisory / Consultancy: Roche. B. Asselain: Advisory / Consultancy: Bristol-Myers Squibb. P. Lamoureux: Full / Part-time employment: Bristol-Myers Squibb. F. Cotté: Full / Part-time employment: Bristol-Myers Squibb. V. Allan: Full / Part-time employment: Bristol-Myers Squibb. M. Daumont: Full / Part-time employment: Bristol-Myers Squibb. N. Ozan: Full / Part-time employment: Bristol-Myers Squibb. C. Calvet: Full / Part-time employment: Bristol-Myers Squibb. M. Perol: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Takeda; Advisory / Consultancy: Clovis. All other authors have declared no conflicts of interest.
1528P - Effectiveness of sequencing TKIs in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC): A French national medical-administrative claim database analysis (ID 1524)
- Nicolas Girard (Paris, France)
Abstract
Background
Treatment of EGFR mutation-positive NSCLC has been revolutionized with the development of EGFR tyrosine kinase inhibitors (TKIs). Three generations of TKIs are now available (1st: erlotinib, gefitinib; 2nd: afatinib, dacomitinib; 3rd: osimertinib). Osimertinib has been developed as second-line treatment after a first-line TKI 1G or 2G when patients progressed with T790M-positive tumors, the most frequent mechanism of resistance. While osimertinib may also be given as first-line treatment, limited data exists on the real life effectiveness of the TKIs sequencing approach: TKI 1G or 2G followed by osimertinib. The French National medico administrative claim database (SNDS) offers the opportunity to estimate the effectiveness parameters for these patients in France.
Methods
Based on SNDS, a historic cohort of patients with a diagnosis of EGFR-mutated NSCLC treated, after a first-line with a TKI 1G or 2G, with osimertinib in second-line between 2015 and 2017 was extracted. Follow-up was conducted until December 31st 2017. Patients’ characteristics, Time on treatments and Overall survival were analysed.
Results
1,404 NSCLC patients have been treated with osimertinib in the database between 2015 and 2017. Among them, 509 had a previous treatment with TKI 1G or 2G without any other anticancer drug before osimertinib initiation, and constitute the analysed population. Mean age was 70.9 (29.1% were above 80 years old), 25.7% were males. Median time on TKI treatment (between the beginning of the first TKI 1G or 2G until discontinuation of osimertinib) was not reached but the percentages of patients still treated were: 83.8% at 24 months and 75.5% at 36 months. Median overall survival was not reached but the percentages of patients still alive were: 79.6% at 24 months and 70.3% at 36 months. Updated data will be presented at the meeting.
Conclusions
Our cohort confirms the prolonged time on TKI treatment and survival rates of patients receiving TKI 1G or 2G followed by osimertinib in a real life setting.
Legal entity responsible for the study
The authors.
Funding
Boehringer Ingelheim.
Disclosure
N. Girard: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): GlaxoSmithKline; Honoraria (self): Hoffmann La Roche; Honoraria (self): Lilly; Honoraria (self): Merck Sharp Dohme; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Takeda. S. Bouee: Full / Part-time employment: CEMKA. D. Moro-Sibilot: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Honoraria (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Honoraria (institution): Roche; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: AbbVie. C. Emery: Full / Part-time employment, CEMKA received a grant from Boehringer Ingelheim to perform the statistical analysis of this study : CEMKA. K. Le Lay: Full / Part-time employment: Boehringer Ingelheim. L. Luciani: Full / Part-time employment: Boehringer Ingelheim. C. Maritaz: Full / Part-time employment: 4. Boehringer Ingelheim. C. Chouaid: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): GlaxoSmithKline; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Takeda; Honoraria (self): Bayer; Honoraria (self): Amgen.
1156P - The clinical significance and biological mechanisms of miR-499a in high-tobacco exposed head and neck squamous cell carcinoma (ID 3407)
- Shiqi Gong (Shanghai, China)
Abstract
Background
Few studies have directly investigated the differential expression of miRNA between low-tobacco and high-tobacco exposed HNSCC. The purpose of this study is to screen the differentially expressed miRNA and to investigate the clinical significance and potential biological mechanisms in above two groups of HNSCC.
Methods
The HNSCC datasets were obtained from TCGA database. Meanwhile, we collected 22 HNSCC patients in our hospital. The differentially expressed miRNAs between low-tobacco and high-tobacco exposed HNSCC were identified based on log2FC > 1 and FDR < 0.05. KM survival analysis, Cox regression, chi-square test were used to evaluate the clinical significance of miRNA. The correlation between gene and clinical characteristic was analyzed by WGCNA. TargetScan, miRDB, DIANA databases were used to predict the target genes of miRNA. RT-qPCR was used to identify miRNA expression in HNSCC tissues. p < 0.05 was considered statistically significant.
Results
30 differentially expressed miRNAs were identified between low-tobacco and high-tobacco exposed HNSCC. The patients with high expression of miR-499a had lower overall survival than those with low expression of miR-499a in high-tobacco exposed HNSCC (p = 0.02). Multivariate Cox regression showed that high expression of miR-499a was an independent risk factor for prognosis of high-tobacco exposed HNSCC (HR = 3.26, p = 0.03). Chi-square test showed that miR-499a was related to N stage in high-tobacco exposed HNSCC (p < 0.01). The clinical significance of miR-499a was not found in low-tobacco exposed HNSCC. WGCNA identified genes associated with N stage in high-tobacco exposed HNSCC. The three databases predicted the target genes of miR-499a, which intersected the genes associated with N stage. ZNRF1, AEBP2, NUS1 were obtained. RT-qPCR showed that miR-499a was differentially expressed between low-tobacco and high-tobacco exposed HNSCC in our own patients.
Conclusions
30 differentially expressed miRNAs are identified between low-tobacco and high-tobacco exposed HNSCC. In high-tobacco exposed HNSCC, highly expressed miR-499a may promote lymph node metastasis by down-regulating one or more of ZNRF1, AEBP2, NUS1, resulting in shortened patient survival.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
The patient’s perspective (ID 499)
- Roger Wilson (Church Stretton, United Kingdom)
Sequencing ALK tyrosine kinase inhibitors: What’s best for our patients? (ID 6270)
- Shirish M. Gadgeel (Ann Arbor, MI, United States of America)
Presentation by expert (ID 69)
- Ignacio Melero (Pamplona, Spain)
1838P - The uptake, patient satisfaction and efficacy of scalp cooling among patients receiving chemotherapy in an Irish oncology day ward (ID 5225)
- William Maher (Cork, Ireland)
Abstract
Background
Chemotherapy-induced alopecia (CIA) is a common and distressing side effect of chemotherapy treatment. Significant progress has been made during the past 2 decades in treating many of the side effects associated with cancer chemotherapy including emesis, hematopoietic cytopenias, xerostomia, infection, pain, and thrombosis. Similar progress has not been made in the prevention of CIA, apart from scalp cooling. We set out to examine the uptake, patient satisfaction and efficacy (as perceived by medical staff and patients) of scalp cooling treatment among patients receiving chemotherapy.
Methods
We reviewed a prospectively maintained database of patients who were offered scalp cooling treatment in our oncology dayward between 01/10/2014 and 22/06/2018. We analysed patient uptake and efficacy as perceived and recorded by medical staff (“medical efficacy”). A questionnaire was sent to patients who had accepted scalp cooling treatment and were alive at follow-up, to assess patient perceived efficacy and patient satisfaction. Patient perceived efficacy was compared to medical efficacy using the Fisher’s exact test.
Results
The mean age was 60.1 (SD 10.9) and 91.4% of the patients were female. Uptake for scalp cooling was 49% (120/245). 75% (90/120) of patients were alive at follow up and 51% (46/90) responded to the questionnaire. Scalp cooling was considered efficacious in 63% (29/46) of patients, versus 43.3% (52/120) as assessed by the medical team, Fishers test p = 0.0253. 86.9% of patients who accepted scalp cooling and responded to the questionnaire (40/46) agreed or strongly agreed that they were satisfied with their choice to try scalp cooling, and 67.4% (31/46) agreed or strongly agreed that their experience of scalp cooling was a positive one. There was a strong association between patient perceived efficacy and satisfaction (p < 0.001).
Conclusions
The use of scalp cooling to prevent chemotherapy induced alopecia is an effective treatment in our real-world population. Patients were more likely than the medical team to consider scalp cooling treatment effective. We found high levels of patient satisfaction with the decision to try scalp cooling, even among patients whose treatment was ineffective.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
395PD - Circulating PD-L1 levels vary across brain tumour entities and are oppositely linked to survival in glioblastoma and lower grade glioma patients (ID 2990)
- Maximilian Mair (Vienna, Austria)
Abstract
Background
Immune therapies targeting the programmed cell death receptor (ligand) 1 (PD-1/PD-L1) axis have shown remarkable activity in a variety of solid tumors. While substantial responses were observed in asymptomatic patients with brain metastases (BM), their clinical activity in primary brain tumors remains limited. In a cohort of adult brain tumor patients, we aimed to analyze soluble PD-L1 (sPD-L1) levels in patient plasma as a systemic marker of tumor - immune system interactions.
Methods
We obtained EDTA plasma from 55 glioblastoma, 26 lower-grade (WHO grade II - III) glioma (LGG), 17 meningioma and 43 BM patients (29/43 lung cancer, 6/43 renal cell carcinoma, 4/43 breast cancer, 4/43 melanoma) as well as 25 controls. sPD-L1 concentrations were measured by a sandwich ELISA using an anti-PD-L1/CD274 antibody (Millipore ABF133) as capture antibody and a non-commercial anti-PD-L1 antibody (clone 5H1) as detection antibody. The lower detection limit as determined by serial dilutions of recombinant human PD-L1 was 0.050 ng/ml.
Results
sPD-L1 was identified in 41/81 (50.6%) glioma, 5/17 (29.4%) meningioma and 6/43 (14.0%) BM patient samples and in 9/25 (36.0%) controls (p = 0.001, Chi-square), with a median concentration of 0.415 ng/ml (range: 0.050 – 42.150 ng/ml). sPD-L1 concentrations were significantly lower in BM as compared to glioma patients (p < 0.001, Mann-Whitney-U) or controls (p = 0.028). There was no observable difference in sPD-L1 concentrations and detectability over WHO grades in glioma and meningioma patients. In BM patients, a trend towards different sPD-L1 levels between primary tumors was seen (p = 0.122, Kruskal-Wallis). sPD-L1 was not correlated to prognosis in meningioma and BM patients. In contrast, glioblastoma patients had longer overall survival (OS) when sPD-L1 was detected (p = 0.006, log-rank). Conversely, sPD-L1 detectability was linked to worse OS in LGG (p = 0.028).
Conclusions
Circulating PD-L1 levels differ between patients with distinct CNS malignancies, suggesting diverse tumor - immune system interactions between primary and secondary brain tumors. Moreover, our results indicate a differential prognostic impact of sPD-L1 in glioma which should be further studied.
Legal entity responsible for the study
The authors.
Funding
Medical University of Vienna.
Disclosure
A. Ilhan-Mutlu: Advisory / Consultancy: MSD; Advisory / Consultancy: Servier. M. Preusser: Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group (GLG); Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.
527PD - Trastuzumab and tucatinib for the treatment of HER2 amplified metastatic colorectal cancer (mCRC): Initial results from the MOUNTAINEER trial (ID 4795)
- John H. Strickler (Durham, United States of America)
Abstract
Background
HER2 (ERBB2) amplification is present in 5-10% of patients (pts) with KRAS and NRAS (RAS) WT mCRC. Tucatinib (Seattle Genetics, Bothell, WA) is a potent, highly selective oral tyrosine kinase inhibitor of the HER2 receptor. In patient-derived xenograft models of HER2+ mCRC, the combination of tucatinib and trastuzumab showed significantly greater antitumor activity compared with tucatinib or trastuzumab alone. Here we present initial results from a trial of tucatinib and trastuzumab in pts with HER2 amplified mCRC.
Methods
MOUNTAINEER is a multicenter open-label single-arm phase II trial. Pts with RAS WT mCRC had HER2 amplification/overexpression by NGS, FISH, or IHC (3+ or 2+ and amplified by FISH). Prior treatment with 5FU, oxaliplatin, irinotecan, and an anti-VEGF antibody was required. Prior anti-HER2 therapy was excluded. Pts received tucatinib 300mg PO bid and standard doses of trastuzumab (IV, Q3 weeks). The primary endpoint was objective response rate (ORR) per RECIST v1.1. Using a 2-Stage Fleming design, this study compared ORR of 20% (null) vs 40% (alt) in 10 or 25 evaluable pts (1-sided α = 0.11; β=.16). At least 8 responses were needed to meet the primary efficacy endpoint.
Results
As of 26 April 2019, 26 pts enrolled, and 22 pts completed ≥1 evaluation of response. 16/26 pts (62%) were male. Median age= 52.5 (range 24-70). The primary tumor site of origin included right colon (N = 4), left colon/rectum (N = 17), transverse colon (N = 3), and overlapping (N = 2). Among 22 evaluable pts, ORR= 55% (CR/PR= 12; SD = 5; PD = 5). Clinical benefit rate (CR+PR+SD≥4 months) = 64%. At a median follow-up of 10.6 months, median PFS= 6.2 months (95% CI 3.5-NE). Median OS = 17.3 months (95% CI 12.3-NE). Median duration of response has not been reached. There were 2 (9%) grade 3 treatment-related adverse events (TRAEs) and no grade 4/5 TRAEs. The most common TRAEs were AST elevation (48%; all G1), ALT elevation (30%; all G1), and diarrhea (26%; G1/G2/G3=4%/17%/4%).
Conclusions
The combination of tucatinib and trastuzumab is well tolerated and has met its primary efficacy endpoint. Based on these results, further expansion of the MOUNTAINEER trial in pts with HER2 amplified mCRC is justified. Updated results will be presented.
Clinical trial identification
NCT03043313.
Legal entity responsible for the study
Academic and Community Cancer Research United.
Funding
Seattle Genetics.
Disclosure
J.H. Strickler: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): Chugai; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: OncoMed; Advisory / Consultancy: Celgene; Advisory / Consultancy: Proteus Digital Health; Advisory / Consultancy: Chengdu Kanghong Biotechnology Ltd; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Leap Therapeutics. A. Cercek: Advisory / Consultancy: Bayer; Advisory / Consultancy: Proteus; Research grant / Funding (institution): Seattle Genetics. C. Wu: Research grant / Funding (institution): Vaccinex; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): FLX Bio. J. Hubbard: Research grant / Funding (institution): Seattle Genetics; Honoraria (institution), Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Treos Bio; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Senhwa pharmaceuticals. N. Kemeny: Research grant / Funding (institution): Amgen. P.M. Boland: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Hemispherx; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Isofol Medical; Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): Athenex; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Clinical Genomics. K. Ng: Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Tarrex Biopharma; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Trovagene; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Pharmavite; Research grant / Funding (institution): Consano. T. Bekaii-Saab: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Seattle Genetics. All other authors have declared no conflicts of interest.