Browsing Over 3689 Presentations
1775P - Incidence of vascular thromboembolism events in cancer patients receiving immunotherapy: A single institution experience (ID 5638)
- Laura Gutiérrez Sainz (Madrid, Spain)
Abstract
Background
Cancer and cancer therapy, such as chemotherapy and vascular endothelial growth factor targeted therapies, have been associated with an increased incidence of vascular thromboembolic events (VTEs): deep venous thrombosis (DVT), pulmonary embolus (PE), arterial thromboembolism (ATE), cerebrovascular accident (CVA), and myocardial infarction. However, the incidence of VTEs in patients on immunotherapy has not been well characterized. The purpose of this study was to assess the incidence of VTEs in cancer patients receiving immunotherapy in our institution.
Methods
We conducted a single institution retrospective cohort study, which included all cancer patients treated with anti PD-1/PD-L1 or anti CTLA-4 therapy from June 2013 to April 2019. Data regarding clinical characteristics, incidence of VTEs and survival were collected.
Results
We selected 229 patients treated with immunotherapy, of whom the majority (n = 146, 63.8%) were males with a median age of 64 years (range 19 to 86 years). Lung cancer was the most frequent tumor treated with immunotherapy (n = 110, 48.0%) followed by melanoma (n = 54, 23.6%) and renal cell carcinoma (RCC) (n = 27, 11.8%). Pembrolizumab was the most commonly used single drug immunotherapy (n = 92, 40.2%) and nivolumab plus ipilimumab was the most common multidrug regimen (n = 17, 7.4%). VTEs occurred in 18 of 229 patients (7.9%). 6 patients had DVT, 7 patients had PE, 3 patients had DVT plus PE, 1 patient had ATE and 1 patient had CVA. 13 of 18 VTEs (72.2%) were symptomatic. VTEs occurred in 12 of 110 patients with lung cancer (10.9%), 5 of 54 patients with melanoma (9.2%) and 1 of 27 patients with RCC (3.7%). In the multivariable analysis, symptomatic VTEs in patients treated with immunotherapy were associated with worse OS (3.6 vs 19.1 months for symptomatic VTEs occurrence vs no occurrence respectively), with statistically significant differences (HR = 2.4 (95%IC: 1.2-4.8) p value: 0.01).
Conclusions
The incidence of VTEs in cancer patients receiving immunotherapy in our sample appears to be consistent with the incidence previously reported. Symptomatic VTEs in cancer patients were associated with worsened survival. Further and prospective studies are needed to derive definitive conclusions.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
315P - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors (ID 4499)
- Evgeny Imyanitov (Saint-Petersburg, Russian Federation)
Abstract
Background
Several lines of evidence suggest the involvement of CCND1 and FGFR1 genes in determining breast cancer (BC) resistance to endocrine therapy, however these assumptions still require a validation in clinical data sets.
Methods
This study included 138 tumors from patients with metastatic BC who received first-line endocrine therapy with aromatase inhibitors (AI, n = 69), tamoxifen (n = 65), goserelin (n = 2) or a combination of goserelin and tamoxifen (n = 2). DNA extracted from formalin-fixed paraffin-embedded archival specimens was tested for CCND1 and FGFR1 amplification by digital droplet PCR.
Results
CCND1 and FGFR1 status was successfully determined in 134 tumors. CCND1 and FGFR1 amplification was detected in 24 (18%) and 28 (21%) informative cases, respectively; 9 carcinomas had concurrent alterations of two genes. Amplifications were more common in less differentiated tumors (G1: 1/18 (6%) vs. G2-3: 34/86 (40%); p = 0.005, Fisher’s exact test). Median disease-free survival in patients receiving AI with CCND1 amplification was shorter than in cases with the normal gene status (12.3 vs. 14.9 months; p = 0.014, log rank test). Objective response to aromatase inhibitors was observed in 2/13 (15%) BC with FGFR1 amplification compared to 22/46 (48%) tumors with the normal FGFR1 gene copy number (p = 0.054). Noteworthy, among patients receiving AI, CCND1 and/or FGFR1 amplification occurred in 5 out of 7 (71%) women with progressive disease compared to only 4 in 23 (17%) patients with objective response to therapy (p = 0.01). Meanwhile, none of 5 tumors showing resistance to tamoxifen harbored CCND1 or FGFR1 amplification.
Conclusions
The presence of CCND1 and/or FGFR1 amplification is associated with worse results of AI therapy in breast cancer patients.
Legal entity responsible for the study
The authors.
Funding
Russian Foundation for Basic Research (grant 17-04-01281).
Disclosure
All authors have declared no conflicts of interest.
Second vote and conclusions (ID 7176)
- Martine Piccart (Brussels, Belgium)
Targeting androgen receptor and Wnt pathway in endocrine-resistant breast cancer. (ID 3572)
- Virginia Figueroa (Buenos Aires, Argentina)
Abstract
Background
Endocrine therapy is the standard treatment for patients with luminal breast cancer. However, after treatment most patients develop hormone resistance, by mechanisms that may include deregulation of growth factor signaling pathways. Fibroblast growth factor 2 (FGF2) consists of a secreted low molecular weight form (LMW-FGF2) and several nuclear high molecular weight forms (HMW-FGF2). We previously demonstrated that FGF2-overexpression in endocrine responsive T47D cell lines, induced hormone resistance. The aim of this study was to explore the mechanisms underlying endocrine resistance.
Methods
We performed RNAseq of FGF2-overexpressing, LMW- and HMW- FGF2-T47D-YA cell lines, compared to control T47D-YA. These results were validated in T47D by qPCR and western blot. Cell proliferation was evaluated by cell counting after 6 day-treatment with enzalutamide (E, anti-androgen), dihydrotestosterone (DHT, androgen) or LGK974 (WNT inhibitor). In vivo, cell lines were subcutaneously transplanted in NSG mice and treated for 3 weeks with E and LGK974.
Results
RNAseq analysis revealed that FGF2-overexpressing cells had a deregulated WNT signaling pathway with the upregulation of several WNT ligands. We also detected decreased estrogen receptor α (ER α) and progesterone receptors (PR) along with an increase in androgen receptors (AR), both at the mRNA and protein levels. We found a more pronounced decrease of PR isoform A (PRA) than isoform B (PRB) resulting in a low PRA/PRB ratio, which is consistent with an endocrine resistant phenotype, based on previous results from our lab. To explore the role of AR and WNT signaling pathways in FGF-triggered endocrine resistance, we evaluated the effect of DHT, E and LGK974 in LMW- and HMW-FGF2-T47D cells compared with T47D control cells. In endocrine resistant cells, DHT induced cell proliferation while blocking AR and WNT pathways inhibited cell proliferation and tumor growth. Conversely, DHT inhibited T47D control cell proliferation and blocking the AR had no significant effect on tumor growth.
Conclusions
Our results suggest that targeting AR and/or WNT pathways may be an alternative therapy for endocrine-resistant breast carcinomas with low PR and high AR levels.
Group psychotherapy: “Psycho-coaching” for oncologists (ID 523)
- Ana Fröbe (Zagreb, Croatia)
CN84 - Health-related quality of life in Greek haematological malignancies patients undergoing chemotherapy (ID 3047)
- Maria Lavdaniti (Thessaloniki, Greece)
Abstract
Background
Recent studies indicate that quality of life plays crucial role in cancer patients’ outcome. In order to obtain a more comprehensive view into this option, we applied three different questionnaires, the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30), the Functional Assessment of Cancer Therapy-general (FACT-G) and the generic Short –Form 36 (SF-36) for registering the haematological malignancies patients’ point of view.
Methods
A cross- sectional study was established involving 67 patients, treated in a large hospital in a major Northern Greek city, with haematological malignancies undergoing chemotherapy in cycle 3. Data was collected using the three aforementioned scales in addition with a questionnaire with demographic and clinical characteristics.
Results
The vast majority of patients were men (n = 42, 62.7%) and married ( 65.7 %, n = 44). Ten out of sixty-seven were multiple myeloma patients (n = 10, 14.9%). The mean scores of overall scales were: SF-36: 47.93±18.84, FACT-G: 73.68±18.25, EORTC-QLQ: 70,70±17.93. Cronbach’s a was >0.70 for all of the subscales of the questionnaires. There is an exception in emotional well being subscale of FACT-G and in physical functional subscale of EORTC QLQ-C30. Also, there was a strong correlation (>0.50) between physical functional subscale and emotional function subscale of the FACT-G, EORTC QLQ-C30 and SF-36 instruments (p < 0.001) and generally between the overall scores of three questionnaires (r = 0.771, p < 0.001 between FACT-G, EORTC QLQ-C30; r = 0.771, p < 0.001 between SF-36 and FACT-G; r = 0.842 p < 0.001 between SF-36 and EORTC QLQ-C30).
Conclusions
The Greek versions of FACT-G, EORTC QLQ-C30 and SF-36 questionnaires are valuable tools that could be easily applied in a daily practical routine for assessing quality of life in patients with hematological malignancies. Additionally, the above procedure provides valid information to the nursing staff in order to help their patients to improve their quality of life having possible influence in the disease outcome.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Chromosome mis-segregation in cancer (ID 93)
- Hiro Funabiki (New York, United States of America)
1336TiP - A randomized phase Ib/II study of the selective small molecule Axl inhibitor bemcentinib (BGB324) in combination with either dabrafenib/trametinib (D/T) or pembrolizumab in patients with metastatic melanoma (ID 2131)
- Oddbjørn Straume (Bergen, Norway)
Abstract
Background
Upregulation of the receptor tyrosine kinase Axl has been linked with both a reduced response to immune checkpoint blockade as well as the development of therapy resistance to BRAF directed therapies in melanoma. Bemcentinib is a first-in-class orally bioavailable selective inhibitor of Axl which is currently being explored in several phase II clinical trials. BGBIL006 (NCT02872259) is an open label phase Ib/II trial designed to explore whether combinations with bemcentinib improves ORR and duration of response compared to standard of care therapies in patient (pts) with metastatic melanoma (MM).
Methods
Patients are randomized 2:1 to receive D/T or pembro +/- bemcentinib, respectively, based on mutation status and tumour load. BRAF positive pts are allowed to switch D/T with pembrolizumab and vice versa upon progression. Tumour responses are assessed per investigator using RECIST v1.1. Plasma protein biomarker levels are measured using the DiscoveryMap v3.3 panel (Myriad RBM) in pts pre-dose and at C2D1. In June 2019, a formal interim analysis of clinical safety and efficacy data will be performed when at least 20 randomised patients have completed up to 12 cycles of treatment. Currently, 50 pts (92 planned) have been enrolled in the trial. Tolerability of the bemcentinib RP2D (200 mg daily) in combination with either D/T or pembro, and AE profiles for either therapeutic approach alone will be reported. Protein biomarkers candidates predictive of pt benefit following treatment and pre/post treatment changes of soluble proteins will be presented. Preliminary efficacy outcome data and safety data from the first formal preplanned interim analysis will be presented together with the recommendations from the Data Monitoring Committee.
Clinical trial identification
NCT02872259.
Legal entity responsible for the study
The authors.
Funding
Research Council Norway.
Disclosure
O. Straume: Travel / Accommodation / Expenses: BerGenBio. J.B. Lorens: Shareholder / Stockholder / Stock options: BerGenBio ASA. G. Gausdal: Full / Part-time employment: BerGenBio ASA. All other authors have declared no conflicts of interest.
Q&A (ID 6236)
LBA33 - Lefitolimod vs standard of care (SOC) for patients with metastatic colorectal cancer (mCRC) responding to first-line standard treatment: Results from the randomized phase III IMPALA trial (ID 5016)
- Ramon Salazar (Hospitalet de Llobregat, Spain)
Abstract
Background
The TLR9 agonist lefitolimod broadly activates the innate and adaptive immune system. Based on encouraging data from the randomized phase II IMPACT trial, lefitolimod was evaluated in this phase III trial as switch maintenance treatment in patients with mCRC who have responded to first-line therapy.
Methods
The international, multicenter, open-label phase III IMPALA trial was conducted including the AIO, TTD and GERCOR cooperative groups and recruited 549 patients across 8 European countries. Patients who had an objective response to any standard first-line induction therapy (5FU/FA or CAPE, plus OX or IRI, alone or plus antiVEGF or antiEGFR) were randomized to receive either lefitolimod monotherapy (experimental arm) or local standard of care (control arm). After first progression, patients started re-induction therapy, with those in the experimental arm continuing lefitolimod on top.
Results
Demographics and baseline characteristics were well balanced between the study arms. Median duration of follow up was 35 months. The primary endpoint overall survival (OS) was not met: median OS was 22.0 and 21.9 months in the lefitolimod and control group, respectively (p = 0.2765; HR = 1.12; 95% CI 0.91 - 1.38). Progression free survival, event-free rates, pre-defined sub-group analyses including molecular and immunological parameters for OS did also not indicate a benefit. In comparison with the control arm treatment with lefitolimod was generally well tolerated. Rates of grade 3, 4 and 5 toxicities were 6.3, 1.9 and 0%, respectively and no new safety signals or autoimmune events were identified while immune activation was confirmed in peripheral blood.
Conclusions
Lefitolimod did not show superiority to standard of care as a single agent maintenance treatment in patients with mCRC. Limited add-on toxicity confirmed the favorable safety and tolerability profile of lefitolimod. Hence, and given its mode of action, lefitolimod will be evaluated in combination with other anti-cancer immunotherapies.
Clinical trial identification
NCT02077868.
Legal entity responsible for the study
Mologen AG.
Funding
Mologen AG.
Disclosure
D. Cunningham: Advisory / Consultancy: Celgene; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Bayer; Advisory / Consultancy: 4SC; Advisory / Consultancy: Clovis; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck. R. Salazar: Advisory / Consultancy: VCN-BCN; Advisory / Consultancy: Agendia; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Roche Diagnostics; Advisory / Consultancy: Ferrer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Prizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche Farma; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: AZD; Speaker Bureau / Expert testimony: Celgene; Leadership role, Shareholder / Stockholder / Stock options: Sace Medhealth; Research grant / Funding (institution): Novartis Farmaceutica; Research grant / Funding (institution): PsiOxus Therapeutics Ltd; Research grant / Funding (institution): VCN Biosciences; Research grant / Funding (institution): Mologen. A. Sobrero: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda. M.P. Ducreux: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Celgene; Research grant / Funding (self): Chugai; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Novartis; Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier; Spouse / Financial dependant: Sandoz. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen. C. Tournigand: Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi. V. Molnar: Full / Part-time employment: Mologen AG. M. Starke: Full / Part-time employment: Mologen AG. M. Baumann: Leadership role: Mologen AG. E. Wiegert: Advisory / Consultancy: Mologen AG. M. Schmidt: Full / Part-time employment: Mologen AG. D. Arnold: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): Amgen; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Terumo; Honoraria (self): Astellas; Honoraria (self): Biocompatibles; Honoraria (self), Advisory / Consultancy: Sirtex; Advisory / Consultancy: Boston Scientific; Honoraria (self): ArtTempi Media; Honoraria (self): PRiME Oncology; Honoraria (self): TRM Oncology; Advisory / Consultancy: IQVIA / Quintiles; Advisory / Consultancy: FlatIron. All other authors have declared no conflicts of interest.
1766P - Efficacy of olanzapine combination in prevention of nausea & vomiting in highly emetogenic chemotherapy (ID 5146)
- Smitha C. Saldanha (Bangalore, Karnatka, India)
Abstract
Background
Chemotherapy Induced Nausea and Vomiting (CINV) is a common phenomenon and various modalities are being looked to reduce this adverse event. Though these modalities better control emesis, nausea is still a problem that is not optimally controlled, thus requiring newer methods to control the same.
Methods
In this study, various combinations of Olanzapine (O), Aprepitant (A), Dexamethasone (D) and 5-HT3 Antagonist (H) were randomized to three groups - standard (AHD), combined (AHDO) & olanzapine (HDO) and compared for efficacy to address the problem of CINV. Patients who had never had any previous chemotherapy and receiving cisplatin, cyclophosphamide–doxorubicin & any other Highly Emetogenic Chemotheraphy (HEC) as per guidelines were enrolled. The standard doses of the concomitant drugs were administered before and after chemotherapy. The two groups receiving Olanzapine were administered 10 mg orally daily on days 1 through 4. Nausea prevention & complete response (no emesis, no use of rescue medication) were primary end points. The toxicity profile and quality of life were secondary end points.
Results
Total of 209 subjects were included in this study (68 in standard (A), 70 in combined (B) & 71 in olanzapine (C) arm). The proportion of patients with no chemotherapy induced nausea was significantly greater in group B than in C & A arm for first 24 hours after chemotherapy (80% (B) v/s 63.23% & 58.9% (A&C); p < 0.01), the delayed period (25-120 hours) after chemotherapy (75.71% (B) v/s 59.23% & 64% (A&C); p < 0.05) and the overall 120-hour period (74% (C) v/s 48% & 52% (A&C); p < 0.01). The complete response rate for vomiting was also significantly increased with group B during the three periods – (85.71% (B) v/s 69.1% & 62% (A&C); p < 0.05), (81 % (B) v/s 70.5% & 68.3% (A&C); p = 0.09, and 77.14% (B) v/s 60.29% & 59.3% (A&C); p < 0.05) respectively. Although there were no significant differences between QTc intervals & blood sugar levels, 5% patients receiving olanzapine had increased sedation (grade 2).
Conclusions
Addition of Olanzapine to the standard arm significantly improved nausea prevention, as well as the complete response for vomiting. This modality may be further studied to determine its efficacy in lower doses so as to negate the effect of sedation.
Legal entity responsible for the study
Kidwai Cancer Institute.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
421P - Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy (ID 4079)
- Gabriela Kramer-marek (Sutton, United Kingdom)
Abstract
Background
Glioblastoma (GBM) employs a variety of mechanisms to suppress the tumour immune microenvironment. A therapeutic approach aiming to abolish immunosuppressive cells and activate anti-GBM immunity would provide a powerful treatment strategy against GBM. We investigated whether photoimmunotherapy (PIT) targeting epidermal growth factor receptor (EGFR) can promoteT cell activation, whilst overcoming the immunologically cold status of GBM.
Methods
The phthalocyanine dye (IR700) was conjugated to affibody molecule (ZEGFR:03115). Cell viability, reactive oxygen species (ROS) production and major damage associated molecular patterns (calreticulin (CRT), heat shock protein 70 (Hsp70), high mobility group box 1 (HMGB1), and ATP) were studied in human and murine glioma cell lines post-ZEGFR:03115–IR700 PIT using flow cytometry (FC), Western blot and ELISA. Maturation of dendritic cells (DCs) stimulated by ZEGFR:03115-IR700 PIT was verified by FC. Xenografts and syngeneic murine tumour models (subcutaneous and orthotopic) were used to determine therapeutic and tumour-specific immune response following PIT. Post-treatment tumours were evaluated ex vivo.
Results
Cells treated with ZEGFR:03115–IR700 PIT showed a significant decrease in cell viability. Generation of ROS post-PIT resulted in translocation of CRT to the cell membrane and the release of HMGB1, Hsp70 and ATP. FC analysis showed significant increase in the surface expression of CD86 and HLA-DR molecules on DCs stimulated by ZEGFR:03115–IR700 PIT compared to the negative controls. In vivo, PIT led to a significant delay in subcutaneous tumour growth. A therapeutic efficacy of the conjugate was observed in brain tumours as early as 24 h post-irradiation. Ki-67, CD31, H&E staining of tumour sections showed a reduced cell proliferation index, distinct differences in vessel density, extensive tumour necrosis and microhaemorrhage on the margins of the treated tumours. In addition, tumour-infiltrating lymphocytes were elevated in the treated mice compared with the controls.
Conclusions
EGFR-targeted PIT is an attractive therapeutic strategy that boosts the anti-tumour T cell response which might influence the suppressed immune microenvironment in GBM patients.
Legal entity responsible for the study
The authors.
Funding
The Institute of Cancer Research; The National Science Centre (NCNOPUS13#2017/25/B/NZ5/00039); and CRUK Convergence Science Centre Fund.
Disclosure
All authors have declared no conflicts of interest.