1596TiPDUBLIN-3, a stage IIIb/IV NSCLC phase (Ph)3 trial comparing the plinabulin (P)/Docetaxel(D) combination with D Alone
AbstractBackgroundThe PD-L1 inhibitors Avelumab (AV) and Atezolizumab (AT) have proven clinical anticancer efficacy, however in NSCLC trials, Javelin Lung 200 (JAV for AV) failed, whereas OAK (for AT) met primary endpoint showing better survival vs 75  mg/m2 D as comparator. The authors suggested JAV trial design factors may have played a role (Barlesi, Lancet Oncology 2018). Firstly, its open-label study design lead to more D patients (pts) dropping out prior to receiving first D dose (8% vs 1% for D vs AV). Secondly, JAV did not stratify for region, resulting in 29% vs 25% Asian pts with D vs AV; Asian pts tend to resp...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

476PUpdated efficacy and safety of entrectinib in patients with NTRK fusion-positive tumors: Integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
ConclusionsIn line with the primary data, these results at an additional 5 months of follow-up show that entrectinib induced clinically meaningful, durable systemic and intracranial responses in pts with NTRK+ solid tumours.Clinical trial identificationALKA, EudraCT: 2012-000148-88 STARTRK-1, NCT02097810 STARTRK-2, NCT02568267.Editorial acknowledgementLaura Vergoz and Charlotte Kennerley, PhD of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche.Legal entity responsible for the studyF. Hoffman-La Roche.FundingF. Hoffman-La Roche.DisclosureC. Rolfo: Leadership role: Educational Committee Member: IALSC -...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

257PMulti-gene prognostic signatures and prediction of pathological complete response of ER-Positive HER2-negative breast cancer patients to neo-adjuvant chemotherapy
ConclusionsIn this in silico analysis, OM, EP and RS prognostic scores were significantly predictive of pCR to neo-adjuvant chemotherapy in ER-positive, HER2-negative breast cancer. Optimal stratification for neo-adjuvant chemotherapy offers the opportunity for personalised care, improved therapy response rates, and reduced ineffective treatment and costs.Legal entity responsible for the studyUniversity College Dublin.FundingThe EI and from the European Union ’s Horizon 2020 research and innovation programme under the Marie Slodowska-Curie grant agreement No. 713654.DisclosureThe author has declared no conflicts of inter...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1150PExpression of immune response biomarkers in head and neck squamous cell carcinoma (HNSCC) in irradiated area
ConclusionsThere were persistence of cytotoxic cells and lower expression of PD-L1 and CD3+ TILs in tumors within irradiated area. This study provides first hypothesis to explain the fact that these lesions are less responsive to immunotherapy although they may still have antitumor capacity. The assessment of predictive biomarkers in patients treated by immunotherapy in randomized trials is required.Legal entity responsible for the studyDr Lionnel Geoffrois.FundingHas not received any funding.DisclosureC. Borel: Honoraria (self): Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Con...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1478OResults of the ASCEND-7 phase II study evaluating ALK inhibitor (ALKi) ceritinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) metastatic to the brain
ConclusionsEfficacy of ceritinib, either in pts with or without a prior exposure to crizotinib, as reported in other studies, is confirmed in this study where only pts with active brain metastases were eligible. Safety profile of ceritinib in these pts remain consistent to what was reported earlier.Clinical trial identificationNCT02336451.Editorial acknowledgementShiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd, Hyderabad, India.Legal entity responsible for the studyNovartis Pharmaceuticals Corporation.FundingNovartis Pharmaceuticals Corporation.DisclosureL.Q. Chow: Advisory / Consultancy, Consultation Honoraria/Revi...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

20PMatrix metalloproteinases and their tissue inhibitors genes abnormal DNA methylation in breast cancer
ConclusionsTaken that HER2-positive BC is a more aggressive disease, one can assume that unsuppressed expression of the MMP2, MMP23B, MMP24, MMP25, MMP28 genes allowed by the absence of abnormal methylation of their promoters is characteristic for less aggressive BCs. Legal entity responsible for the study: Research Centre for Medical Genetics. Funding: The research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation.Legal entity responsible for the studyResearch Centre for Medical Genetics.FundingMinistry of Science and Higher Education of the Russian Federatio...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

258PImpact of menopause status on breast cancer outcomes and amenorrhea incidence during adjuvant tailored dose dense chemotherapy
ConclusionsTdd EC/D was associated with non-significant improvements in BCRFS, regardless of menopause status, without increasing rates of CIA. Negative effect on TNBC could be a chance finding due to low number of patients but the results warrant caution and necessitate further investigation.Legal entity responsible for the studyThe authors.FundingSwedish Cancer Society, Swedish Breast Cancer Association (BRO), Radiumhemmet Research funds, Amgen, Roche, Sanofi-Aventis.DisclosureG. Steger: Honoraria (self): Amgen. R. Greil: Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): MS...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

477PAn international randomized cross-over bio-equivalence study of oral paclitaxel + HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumours
ConclusionsOraxol (oral paclitaxel + HM30181) given daily for 3 days can show bio-equivalence to single dose of IV paclitaxel 80mg/m2 at 80% power with 90% CI of the GMR within the limits of 80 – 125%.Clinical trial identificationACTRN 12615000894594.Legal entity responsible for the studyAthenex.FundingAthenex.DisclosureC.G.C.A. Jackson: Travel / Accommodation / Expenses: Athenex. N.A. Hung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Zentech. D. Cutler: Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex. D. Kramer: Full / Part-time employment: Athenex. J. Zhi: Ful...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1151PHLA-ligandome analysis reveals target antigens of oropharyngeal squamous cell carcinoma
ConclusionsThe analysis of HLA-ligandomes from OPSCC revealed tumor-exclusive and newly discovered antigens. We found clear differences between the HLA ligandomes of HPV+ and HPV- patients. These differences need to be taken into account for therapeutic vaccination strategies. The level of personalization needed for such vaccines remains to be determined.Legal entity responsible for the studyThe authors.FundingUniversity of Ulm, Clinician Scientist Programme.DisclosureS. Laban: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp& Dohme (MSD); Honoraria (institution), Advisory...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

21PUveal melanoma cell lines depend on multiple signaling pathways for survival
ConclusionsThe sensitivity of GNAQ/11 mutation UM cell lines to 6 targeted drugs is heterogeneous and no single dominant signalling pathway was identified. This suggest that multiple, independent signal pathways contribute to the survival of UM. Thus, inhibition of any single pathway is unlikely to be effective in the treatment of majority of metastatic UM. Table:21P Summary of UM cell lines to each inhibitor. Combined result of cell viability assay and cell cycle analysisCell LineMutationTrametinibBEZ235NAV2729AEB071VerteporfinLXS196Mel270GNAQsensitivesensitivesensitivesensitivesensitivesensitiveOMM1GNA11resistantsensitiv...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

259PProgesterone receptor isoform ratio dictates antiprogestins/progestins effects on metastatic breast cancer models
ConclusionsProgestins/antiprogestins stimulate or inhibit, respectively tumor growth/metastasis of mammary carcinomas with high PRA/PRB ratio, and they may exert opposite effects in tumors with low PRA/PRB ratio. These findings highlight the relevance of evaluating PR isofor.m ratio prior to PR ligand treatment on human breast cancer.Legal entity responsible for the studyCONICET.FundingCONICET; INC, ANPCYT.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

478PClinical evaluation of drug-eluting bead transcatheter arterial chemoembolization(D-TACE) versus conventional TACE in treatment of unresectable hepatocellular carcinoma
ConclusionsIn unresectable HCC, transcatheter treatment with DEB loaded with doxorubicin offers a better objective tumor response than conventional TACE, especially in patients with tumor size less than 7cm and tumor numbers less than 3.Legal entity responsible for the studyThe author.FundingHas not received any funding.DisclosureThe author has declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1598PEscalation plans and DNACPR discussions in the unwell oncology patient
ConclusionsEmpowering junior doctors and simple departmental changes lead to a significant improvement in communicating and implementing DNACPR decisions. We therefore significantly reduced unnecessary CPR attempts and subsequently improved communication and documentation of escalation plans and prognosis. We believe our model can be implemented in other oncology centres and look forward to discussing this further.Legal entity responsible for the studyNational Health Service, UK.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

22PXAF1 and ZNF313 complex stimulates ER stress-induced apoptosis via direct GRP78 inhibition
ConclusionsConclusion: XAF1 sensitizes cells to ER stress and drives apoptotic switch of UPR function away from cell cycle arrest by directly antagonizing GRP78 through the assembly of a ZNF313-mediated destruction complex. Our study identifies first a cell-fate decisions function of XAF1 under ER stress conditions.Legal entity responsible for the studySung-Gil Chi.FundingBK.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1152PTopographical distribution of sentinel lymph nodes in early tongue squamous cell carcinomas
ConclusionsSLNB is a minimally invasive and highly reliable method staging the cN0 for patients with early OSCC. Completion neck dissection of level I-III in SLNB-positive patients might be sufficient in patients with early TSCC. Our study showed that SLNB was helpful in clarifying unexpected bilateral or contralateral metastatic drainage patterns. SLNB provides more accurate staging than elective neck dissection or wait and see policy.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research