Browsing Over 3689 Presentations
CN44 - Standardized nursing care in the department of radiotherapy of a network of cancer centres (ID 2789)
- José Delgado (Hospitalet de Llobregat, Spain)
Abstract
Background
The Catalan Institute of Oncology (ICO) is a specialised cancer institution. It has four centres distributed around Catalonia that covers 45% of the adult cancer patient population in the autonomy. In three of them exists a radiotherapy department: L’Hospitalet, Badalona and Girona; with 11 accelerators altogether. Near 6.000 patients per year receive treatment in them. All radiotherapy departments in Spain need to accomplish with a quality system. ICO has a system based in International Organization for Standardization (ISO) regulations. Recently, a new system of ISO certification (ISO 9001:2015) has required increasing the homogenization level among our three departments. In addition, ICO promotes equality in access to services and assistance. For all these reasons it was developed the “Standardize project of the assistance procedures in Oncologic radiation”.
Methods
The ISO whole process was divided in 6 sub processes. In each center there was a group of professionals who works with every sub process and discuss with the other hospitals in order to define the common procedures. In February 2018, we started a work plan to do it through teleconference meetings. Nurses and radiotherapist technicians were included and nominate several leaders in each of the working groups which involved their activity. Meeting works ended in June 2018. From then until 2019 July we run with the implementation time.
Results
Nurses and radiotherapist technicians of the three institutions defined the list of agreements and consensus to do: homogeneous written education for patients to implement the active identification with patients Image guided radiotherapy protocols (IGRT) protocols for management break on treatments & short interruptions safety check list for the first session patient follow-up, alternating nurses and physicians nurse appointment at the end of treatments quality indicators for activity & schedules.
Conclusions
This project has assured that population from 3 different areas will receive same treatments, under equal circumstances. We incorporated strengths of each centre, using now a unique map of the process of radiotherapy. Furthermore we share same safety and prevention standards and a prospective system for risk analysis.
Legal entity responsible for the study
Institut Català d’Oncologia.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
1238P - Genomic correlates of response to anti-PDL1 atezolizumab in non-small cell lung cancer OAK and POPLAR trials (ID 1898)
- Hari Singhal (Basel, Switzerland)
Abstract
Background
Limitations of integrating biological knowledgebases with genomics impedes the development of predictive correlates that would help in personalization of immunotherapy. Non-small cell lung cancer (NSCLC) patients treated with atezolizumab, an antiprogrammed death-ligand 1 (PDL1) antibody, have better overall survival when compared to patients receiving docetaxel chemotherapy in Poplar (Lancet, 2016) and Oak (Lancet, 2017). We hypothesized that patterns in the mutations of immune signatures would correlate with the immunotherapeutic effect of atezolizumab in NSCLC.
Methods
Sequencing data from Poplar (n = 277 patients) and Oak (n = 725 patients) trials was analyzed for understanding genomic alterations in relation to patient outcomes. Signatures from publicly-available knowledgebases were integrated with the genomics and clinicopathological data into an algorithm for identifying patterns correlative of immunotherapeutic response.
Results
Patients benefitting from atezolizumab were more likely to have mutations in oncoimmunity-related genes which were significantly overlapping between the two trials. These overlapping genes were used to develop a de novo signature comprising of CDKN1A, ERRFI1, JAK2, NOTCH2, ACVR1B, NFKBIA, GNA13, MERTK, BTG1, CDKN1B, FOXP1, PDK1, ETV6, MLL2, SMAD3, DICER1 and BRCA2. Mutations in any of the genes within the signature identified patient subpopulations with higher immunotherapeutic response to Atezolizumab in both Oak (HR = 0.3, P = 1.8e-6 versus HR = 0.76, P = 5.5e-3 for entire cohort) and Poplar (HR = 0.18 and P = 3.6e-2 versus HR = 0.71, P = 0.023 for all patients) trials. Prediction efficiency of the signature was significantly better than established biomarkers such as PDL1 staining (Nature, 2014) in both Oak (HR: 0.58 and P = 1.8e-6) and Poplar (HR: 0.58 and P = 0.04) trials indicating that genomic correlates could add significant value to existing modalities in predicting immunotherapy response.
Conclusions
In summary, integration of biological knowledgebases with genomics suggests that a rheostat of mutational burden in non-overlapping genesets is associated with immunotherapeutic effect and identifies novel genomic correlates for response to Atezolizumab.
Clinical trial identification
NCT02008227; NCT01903993.
Legal entity responsible for the study
Roche.
Funding
Roche.
Disclosure
D.R. Gandara: Research grant: Bristol-Myers Squibb, Roche-Genentech, Novartis, Merck; Consultancy: AstraZeneca, Celgene, CellMax Life, FujiFilm, Roche-Genentech, Guardant Health, Inviata, IO Biotech, Lilly, Liquid Genomics, Merck, Samsung Bioepis, Pfizer. All other authors have declared no conflicts of interest.
769P - Prognosis of esophageal squamous cell carcinoma based on local immunity evaluation (ID 4293)
- Elena Y. Zlatnik (Rostov-on-Don, Russian Federation)
Abstract
Background
The purpose of the study was to assess the significance of the local cytokine composition in patients with esophageal squamous cell carcinoma (EC) for the disease prognosis.
Methods
Cytokines were studied in tumor, peritumoral (PT) and resection line (RL) tissues of 36 patients with stage II-III EC. All patients received surgery; further treatment depended on the tumor stage. During the observation, patients were divided into groups with short and prolonged progression-free survival (< and >1.5 years). Levels of TNF-α, IL-1b, IL-6, IL-8, and IL-10 were determined in tissue homogenates by ELISA and calculated in pg/mL/g of protein. Discriminant and ROC analyses were performed with the calculation of the area under a ROC curve (AUC) and cut-off points for statistically significant indicators sharing with maximum diagnostic sensitivity (DSe) and specificity (DSp) two alternative signs: the presence or absence of the risk of early progression.
Results
Patients showed different initial levels of tissue pro-and anti-inflammatory cytokines. PT of patients with the further progression was characterized by higher levels of TNF-α (by 1.9) and IL-10 (by 1.6 times), and their tumor tissues – by 2.1 times higher IL-1b and 1.6 times higher IL-8 (p < 0.05). The ROC analysis demonstrated the following cut-off values: in tumors 57.5 pg/mL/g (IL-1b) and 4.5 pg/mL/g (IL-10), in PT 36.0 pg/mL/g (IL-8) and 7.4 pg/mL/g (TNF-α), in RL 9.8 pg/mL/g (TNF-α) and 5.2 pg/mL/g (IL-10). Exceeding them involved the risk of early disease progression. Levels of TNF-α in PT, IL-10 in tumors and RL showed good (AUC 0.8-0.9), and levels of TNF-α in RL, IL-1b in tumors and IL-8 in PT - satisfactory (AUC 0.7-0.8) ability to recognize the risk of early EC progression, p < 0.005.
Conclusions
Evaluation of local levels of cytokines allowed identifying the risk criteria for the development of early progression of EC, which along with clinical signs (the process spread) determine its prognosis.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
1389P - Analysis of PD-1/PD-L1 blockade biomarker and immune infiltrates in gastroenteropancreatic neuroendocrine carcinoma (ID 1234)
- Jia Zhang Xing (Beijing, China)
Abstract
Background
Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly differentiated grade 3 neuroendocrine neoplasm, of which the overall survival is poor with limited treatment options. Immune checkpoint related therapy such as PD-1 blocking has successfully been used in some solid tumor treatment. In this study, we investigated the infiltration of immune-cells and PD-1/PD-L1 blockade biomarkers to improve understanding of the tumor immune microenvironment in GEP-NEC.
Methods
Stromal and tumor cells expressing CD3, CD8 and CD68 protein were assessed in 32 cases of GEP-NEC by immunohistochemistry. Their tumor mutational burden (TMB) and microsatellite instability (MSI) were measured by gene sequencing. Software mSINGS MSIsensor and MSIseq were used to evaluate MSI and MSI status was set when more than two software showed the MSI. The Mann-Whitney U test and Kruskal-Wallis test were used to analyze the correlation of markers expression with clinicopathological parameters. Kaplan -Meier curves were applied in survival analyses.
Results
In the study, 65.6% of the patients were male and the median age was 65. The predominant primary sites were stomach (66%) and pancreas (19%). High infiltration (more than 25% stromal area infiltration) of CD3, CD8 and CD68 immune cells were found in 84%, 47% and 81% of the patients, respectively. High expression of CD3 correlated with high expression of CD8 and CD68 (p < 0.05). Average of TMB was 5.84 mutations per megabase. 57% of the patients were classified as having intermediate TMB (5-15 mutations/megabase) with the remaining classified as having low TMB (0-5 mutations/megabase). None of the patients was in MSI status under our evaluation. Among the baseline characteristics, patients in stage IV of TNM showed lower CD8 expression (p < 0.05). No significant association was observed between the investigated markers and survival.
Conclusions
The study contributes to the understanding of immune microenvironment of GEP-NEC. The association of clinicopathological features with PD-1/PD-L1 blockade biomarkers and immune cells in GEP-NEC were explored. This understanding should help to improve predictions of the impact of the PD-1/PD-L1 pathway in GEP-NEC patients.
Legal entity responsible for the study
The authors.
Funding
Chinese Academy of Medical Sciences (CAMS) Initiative for innovative Medicine (CAMS-I2M) 2017-I2M-1-001.
Disclosure
All authors have declared no conflicts of interest.
1574P - Survival prolongation by rationale innovative genomics (SPRING): An international WIN consortium phase I study exploring safety and efficacy of avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer (NSCLC) with integrated genomic and transcriptomic correlates (ID 3390)
- Benjamin Solomon (Sioux Falls, SD, United States of America)
Abstract
Background
In prior published work, the Worldwide Innovative Network (WIN) Consortium described the Simplified Interventional Mapping System (SIMS) algorithm, based on the hypothesis that both genomic and transcriptomic data are important for matching to a tri-therapy regimen. To account for variation in transcription levels between different tissues, gene by gene tumor RNA levels are normalized against RNA levels in analogous biopsied normal tissue. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced NSCLC.
Methods
Patients with metastatic NSCLC (no EGFR or ALK alterations; no ROS1 alteration if tested; PD-L1 unrestricted; ≤2 prior therapy lines) were treated with avelumab, palbociclib, and axitinib (3 + 3 dose escalation design). After consent, biopsies of tumor and normal endobronchial mucosa were obtained on all patients for analysis on a central genomics/transcriptomics platform and retrospective SIMS algorithm validation. A safety monitoring committee reviews study conduct at least weekly.
Results
Twelve patients have been treated (3 at dose level 1; 6, dose level 2; 3, dose level 3). Three dose-limiting toxicities (DLTs) at least possibly drug related occurred: 1 DLT at dose level 2 (Grade 3 (G3) infusion reaction); 2 DLTs at dose level 3 (G3 hand/foot syndrome and a G5 respiratory failure). The partial response (PR) rate was 44% (4/9 patients who have reached restaging including 2/3 patients at dose level 1; two PRs are in patients who failed prior pembrolizumab). The maximum tolerated dose was avelumab 10 mg/kg IV q2weeks, axitinib 5 mg po bid, palbociclib 75 mg po daily (7 days off; 21 days on) (dose level 2).
Conclusions
The tri-therapy combination of avelumab, axitinib, and palbociclib is tolerable with early evidence of activity including in NSCLC patients who failed a prior checkpoint inhibitor. Expansion cohorts are being added to further explore safety of a recommended phase II dose. Transcriptomic and genomic correlates of response are being assessed.
Clinical trial identification
NCT03386929; First posted: December 29, 2017.
Legal entity responsible for the study
Worldwide Innovative Network (WIN) Association - WIN Consortium.
Funding
ARC Foundation for Cancer Research and Pfizer.
Disclosure
B. Solomon: Travel / Accommodation / Expenses: Elekta. A. Callejo: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boerhinger; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Speaker Bureau / Expert testimony: KYOWA KIRIN ; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Celgene. J. Bar: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Genentech; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Takeda; Advisory / Consultancy: Vascular Biogenics; Research grant / Funding (institution): MedImmune. G. Berchem: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Celgene. L. Bazhenova: Advisory / Consultancy: Takeda; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Loxo Oncology; Shareholder / Stockholder / Stock options: Epic Sciences; Research grant / Funding (institution): Beyondspring Pharma. P. Saintigny: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): HTG Diagnostics. E. Raymond: Full / Part-time employment: Genoscience; Full / Part-time employment: Scor; Advisory / Consultancy: Pharmaengine; Travel / Accommodation / Expenses: Merck. N. Girard: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Takeda; Advisory / Consultancy: GSK; Advisory / Consultancy: AbbVie. R. Sulaiman: Full / Part-time employment: Physicians Laboratory . E. Rubin: Travel / Accommodation / Expenses: Roche. V. Lazar: Licensing / Royalties: Worldwide Innovative Network Association. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: ABBVIE; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blue Print Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck MGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Domme; Advisory / Consultancy, Speaker Bureau / Expert testimony: NOVARTIS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: JANSSEN; Research grant / Funding (institution): Fundation Merck Salud; Research Grant / Funding (Institution): Grant For Oncology Innovation Emd Serono. A. Onn: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. B. Leyland-Jones: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Exelixis; Speaker Bureau / Expert testimony: Genentech; Speaker Bureau / Expert testimony: Puma; Travel / Accommodation / Expenses: NFCR; Travel / Accommodation / Expenses: AkesoGen. R. Kurzrock: Shareholder / Stockholder / Stock options, Co-founder: CureMatch; Shareholder / Stockholder / Stock options: IDbyDNA; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Soluventis; Advisory / Consultancy: Gaido; Advisory / Consultancy: Loxo Oncology; Advisory / Consultancy: Xbiotech; Advisory / Consultancy: Acurate Therapeutics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: NeoMed; Research grant / Funding (institution): uardant Health; Research grant / Funding (institution): Grifols; Research grant / Funding (institution): Konica Minolta; Research grant / Funding (institution): OmniSeq; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sequenom; Research grant / Funding (institution): Foundation Medicine. All other authors have declared no conflicts of interest.
Welcome and introduction (ID 6480)
- Nicola Fazio (Milan, Italy)
General discussion (ID 377)
1264P - Changes of TCR repertoire in metastatic renal cell carcinoma and metastatic melanoma patients treated with nivolumab (ID 5758)
- Martin Klabusay (Olomouc, Czech Republic)
Abstract
Background
Renal cell carcinoma and melanoma are common cancers with growing incidence rates. Nivolumab, anti-programmed-death 1 protein (PD1) antibody selectively blocks the interaction between PD-1 and its ligand PD-L1 and enables a restart of the immune response against cancer cells, significantly improving survival in both treatment-naïve and pretreated patients with metastatic renal cell carcinoma (mRCC) and metastatic melanoma. It was hypothesized that proliferation of specific T cell clones may be associated with response to anti-PD1 therapy. The aim of this study was to analyze T cell repertoire.
Methods
Blood samples of 10 patients with mRCC and 12 patients with metastatic melanoma were evaluated and compared to 14 healthy controls. All mRCC patients were treated with nivolumab after prior interferon α, sunitinib, pazopanib, everolimus or axitinib. Mononuclear cells were isolated from the peripheral blood on Histopaque. Cells were stained with directly labeled anti-CD3 PerCP-Cy5.5, anti-CD4 APC, anti-CD8 APC-Cy7 and anti-TCR FITC and PE antibodies. In total, 24 Vß TCR families were evaluated. Measurement was performed by multicolor flow cytometry. Data were analyzed with Wilcoxon non-parametric test and principal component analysis.
Results
Significant changes in following TCR families (p < 0.001) were confirmed: an increase of CD4+ cells Vß16, Vß20, a decrease of CD4+ cells Vß17 and CD8+ cells Vß5.1, Vß5.3, Vß7.1, Vß22. In several patients, highly enriched individual populations of CD4+ together with CD8+ cells were observed. CD4+ Vß21.3 was increased significantly in mRCC patients while decreased in melanoma patients.
Conclusions
Significant changes in TCR repertoire were observed in mRCC and melanoma patients treated with nivolumab compared to healthy controls. The changes were different between mRCC and melanoma patients as shown on principal component analysis biplot. Very high levels of CD4 and CD8 lymphocytes with defined TCR Vß families were identified in several patients. Clonal expansion of CD4+ and CD8+ cells is related to nivolumab treatment and it is likely to correlate with the response to treatment.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Q&A led by Discussant (ID 6693)
966P - Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma (ID 2405)
- Felix Lefort (Bordeaux, France)
Abstract
Background
Nivolumab is a standard of care in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) after failure of prior anti-angiogenic tyrosine-kinase inhibitors (TKIs). We evaluated the impact of corticosteroids (CS) during nivolumab in pts with mccRCC as part of a prospective clinical trial.
Methods
We conducted an ancillary study of the GETUG-AFU 26 NIVOREN study (NCT03013335), a multicenter prospective phase II safety study of nivolumab in mccRCC after progression on anti-angiogenic TKIs. Patients receiving CS at nivolumab initiation were excluded. Overall survival (OS) and progression free survival (PFS) of pts exposed to CS (≥ 10 mg of prednisone equivalents) or not during nivolumab were assessed. To overcome immortal time bias, we used two different landmark analysis methods. We first excluded pts who progressed or died before specified landmark timepoints (12 and 16 weeks). In a second method, patients treated with CS before landmark timepoints (12 and 16 and 24 weeks) were used to evaluate the effect of an early exposition to CS.
Results
Among the 665 evaluable pts, with a median follow up of 23.9 months, 113 (17 %) were exposed to CS during nivolumab, mainly to treat immune-related adverse events of any grade (74%). Other indications included infections (15%), complications of radiotherapy and chronic obstructive pulmonary disease. Median time to the first CS treatment was 21.6 weeks. Using a landmark at 12 weeks, OS rate at 12 months were 85.6% and 73.5% in pts exposed or not to CS [hazard ratio (HR), 0.57; p = 0.0017]. PFS rate at 12 months were 61.1% and 41.6% in pts exposed or not to CS (HR, 0.63; p = 0.0065). Landmark analyses at 16 weeks showed similar results. With the second landmark method, no differences in PFS or OS were observed between groups at 12 and 16 weeks. With a landmark set at 24 weeks, OS was similar in pts exposed or not to CS (HR, 1.14; p = 0.55).
Conclusions
The use of CS during nivolumab in mccRCC is not associated with a detrimental effect on survival outcomes. The positive association of corticosteroid use for irAEs with outcomes was not confirmed by second landmark modalities. Immortal time bias should be carefully considered when studying time-dependent variable.
Clinical trial identification
NCT03013335.
Legal entity responsible for the study
UNICANCER.
Funding
Bristol-Myers Squibb.
Disclosure
M. Gross-Goupil: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis. B. Laguerre: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): Ipsen. P. Barthelemy: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Sanofi. S. Negrier: Honoraria (self): Pfizer; Honoraria (self): Bms; Honoraria (self): Novartis; Honoraria (self): IPSEN; Honoraria (self): Euspharma. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck. S. Ladoire: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS. M. Laramas: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: SANOFI; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: IPSEN; Speaker Bureau / Expert testimony: Janssen; Travel / Accommodation / Expenses: Eisai. S. Oudard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; 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: Ipsen. B. Escudier: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Advisory / Consultancy, Research grant / Funding (institution): Avevo; Advisory / Consultancy, Research grant / Funding (institution): Pfizer. L. Albiges: Advisory / Consultancy, Compensated to institution: Pfizer; Advisory / Consultancy, Compensated to institution: Novartis; Advisory / Consultancy, Compensated to institution: BMS; Advisory / Consultancy, Compensated to institution: Ipsen; Advisory / Consultancy, Compensated to institution: Roche; Advisory / Consultancy, Compensated to institution: MSD; Advisory / Consultancy, Compensated to institution: AstraZeneca. All other authors have declared no conflicts of interest.
1116PD - A window of opportunity trial of preoperative nivolumab with or without tadalafil in squamous cell carcinoma of the head and neck (SCCHN): Safety, clinical, and correlative outcomes (ID 4782)
- Adam J. Luginbuhl (Philadelphia, United States of America)
Abstract
Background
Tadalafil is a phosphodiesterase-5 inhibitor was found to decrease MDSC, Treg, arginase and iNOS expression with an increase in cytotoxic effector T cells. In order to improve on the clinical efficacy of PD-1 blockade platform, we designed a window of opportunity trial to test the immunological and therapeutic effects of nivolumab and tadalafil combination.
Methods
We conducted an investigator-initiated, two-arm multi-institutional window of opportunity randomized trial in patients with SCCHN of any stage, who were candidates for complete surgical resection (NCT03238365). Subjects in the two cohorts received nivolumab 240 mg intravenously on day 1 and 15 followed by surgery on day 28. Subjects in the combination cohort received tadalafil 10 mg p.o. once daily for 4 weeks. Patients were stratified to HPV status. Imaging, blood and tumor were obtained pretreatment and post treatment and used for immunological correlatives. The primary endpoint was correlative analysis of immune cell polarization. We present results with complete study accrual.
Results
Of 47 randomized patients, 21 had HPV + tumors. 45/47 patients completed the treatment regimen. Grade 3 serious adverse event (SAEs) occurred in 18% of pts. No related AE’s resulted in delay of surgery. Preliminary evaluation of pathologic treatment effect (TE) was assessed on post treatment specimens showing that 25% of pts demonstrated no treatment effect (TE), 25% had 1-20% TE, 41% had 21-99%TE and 9% had CR. Patients receiving tadalafil amplified intratumoral transcript levels consistent with enhanced myeloid infiltration and T cell activation. This was associated with changes in cytokine levels in patients sera consistent with altered myeloid phenotypes.
Conclusions
Nivolumab +/- tadalafil demonstrated a range of treatment responses with 50% of pts having a pathologic TE > 21% in 4 weeks. In the context of PD-1 blockade, tadalafil enhanced T lymphocyte and myeloid cell infiltration. The mechanisms underlying this shift warrant further investigation.
Clinical trial identification
NCT03238365.
Legal entity responsible for the study
The authors.
Funding
Bristol-Myers Squibb.
Disclosure
All authors have declared no conflicts of interest.
371P - Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2- breast cancer in Germany: Interim results of the INGE-B phase II study (ID 1423)
- Diana Lüftner (Berlin, Germany)
Abstract
Background
In the PALOMA-3 trial, palbociclib plus fulvestrant demonstrated a clinically meaningful improvement in overall survival compared with fulvestrant plus placebo in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer who had relapsed or progressed on prior endocrine therapy (Turner NC et al., NEJM 2018). Detailed analyses for first-line (1L) and second- or later- line (2L+) therapy are still limited.
Methods
The prospective, multicenter phase 2 INGE-B trial was designed to generate efficacy and safety data on the combination of palbociclib with letrozole (1L) or fulvestrant (1L, 2L+) in accordance with the PALOMA trials and to generate so far lacking trial data on the combination of palbociclib with anastrozole (1L), exemestane (1L) or letrozole (2L+). This pre-planned interim analysis was conducted to evaluate data on pts receiving palbociclib plus fulvestrant as 1L or 2L+ therapy. The primary endpoint was the clinical benefit rate (CBR) in pts with measurable disease according to RECIST v1.1. Key secondary endpoints included the overall response rate (ORR), the CBR for all pts, and safety. Data were analyzed with descriptive statistics.
Results
At the cut-off date of the interim analysis (Dec 17, 2018), 124 pts have been recruited from 03/2017 through 06/2018 at 47 sites across Germany to receive palbociclib plus fulvestrant (1L: 57 pts; 2L+: 67 pts). 57 of 67 pts treated in 2L+ were evaluable. Median age was 68.0 years, 91.2% (n = 52) of pts had an ECOG performance score of 0 or 1. 28.1% (n = 16) of pts presented with non-measurable bone-only disease. The CBR was 35% (n = 14) for the 40 pts with measurable disease (RECIST v1.1) and 51% (n = 29) for all pts (investigator assessment). The ORRs were 25% (n = 10) and 21% (n = 12), respectively. Grade 3/4 adverse events experienced by at least 10% of pts were neutropenia (n = 21, 36.8%) and leukopenia (n = 7, 12.3%).
Conclusions
This INGE-B interim analysis showed a remarkable clinical benefit for palbociclib plus fulvestrant as second- or later-line therapy for pts with HR+/HER2- advanced breast cancer. No new safety signals were detected.
Clinical trial identification
2015-001603-32.
Legal entity responsible for the study
iOMEDICO AG.
Funding
Pfizer Pharma GmbH.
Disclosure
D. Lüftner: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Teva; Advisory / Consultancy: Tesaro; Advisory / Consultancy: L’Oréal; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca. M.K. Welslau: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: GILEAD; Honoraria (self), Advisory / Consultancy: HEXAL; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Medac; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): Astellas; Honoraria (self): AstraZeneca. A. Welt: Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Eisai; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. M. Zaiss: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis. N.W. Marschner: Leadership role, Shareholder / Stockholder / Stock options: iOMEDICO AG; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.