Browsing Over 990 Presentations
Keynote 1 - Cancer burden in the Asia-Pacific region
- Elisabete Weiderpass
- Elisabete Weiderpass
Keynote 2 - Innate immunity, inflammation and cancer: The long journey to bedside
- Alberto Mantovani
- Alberto Mantovani
Singapore Cultural Dance performance
Welcome address by the ESMO President
- Josep Tabernero
- Josep Tabernero
Welcome address by the Senior Minister of State, Ministry of Transport & Ministry of Health
- Pin Min Lam
- Pin Min Lam
Welcome address by the President of the Singapore Society of Oncology
- Su Pin Choo
- Su Pin Choo
Presentation of Token of Appreciation to the endorsing National Oncology Societies
- Josep Tabernero
- Josep Tabernero
Scientific address
- Rebecca Dent
- Ian Chau
- Rebecca Dent
- Ian Chau
404O - A phase II single arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated Classical Kaposi Sarcoma (CKS)
- Alona Zer
- Alona Zer
- Oded Icht
- Oded Jacobi
- Eyal Fenig
- Sivan Shamai
- Ofer Merimsky
- Ronnie Shapira
- Hanna Bernstine
- Rony Weitzen
- Olga Vornikova
- Eytan Ben-Ami
- Gil Bar-Sela
- Salomon M. Stemmer
- Michal Lotem
Abstract
Background
CKS is an angioproliferative mesenchymal neoplasm causatively associated with human herpes virus 8 infection. Though recombinant IFNa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated (tx) progressive CKS.
Methods
CKS pts with progressive disease after > 1 line of systemic tx and measurable disease by PET/CT and/or physical exam received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint (EP) was overall response rate (ORR), secondary EP include 6-months progression free survival rate (PFS) and safety. Exploratory EP included PD-L1/MMR IHC, DNAseq (596 genes)/RNAseq (whole transcriptome) of tissue and matched blood to explore CKS genomic traits and IO correlates: TMB, MSI, dMMR, PD-L1, immune gene expression (PD1, CTLA4, etc) (Tempus Labs, Chicago, IL, USA).
Results
Twelve patients were enrolled and evaluable between Apr2018-Jun2019 and 11 were evaluable for response. Median age 72 (61-81). At a mFU of 6 months ORR was 45% (4 pts PR, 1 pt CR, 6 pts SD). mPFS was not reached, 6-mo PFS rate was 91% (1 out of 11 patients had PD). The safety profile was as expected with three patients with G2 toxicity (1 ALT/AST increase, 1 asymptomatic lipase increase) and two patients with G3 toxicity (1 colitis, 1 asymptomatic lipase increase) . One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in one pt (G2 LFT increase. maintaining CR 4 months after treatment discontinuation). Correlative results are available for four patients showing negative PDL1 IHC in all, low TMB, MS-S, but marked overexpression of CTLA4, PD1 and PDL1.
Conclusions
The interim analysis in this prospectively designed phase II study of nivo/ipi demonstrate promising activity in progressive CKS, with 45% ORR and a 6mo PFS rate of 91%. Toxicity profile as expected in this class of drugs. Correlative studies are preliminary but warrants further investigation into immune gene expression profiles.
Clinical trial identification
NCT03219671.
Editorial acknowledgement
None
Legal entity responsible for the study
The authors.
Funding
BMS Rabin Medical Center.
Disclosure
A. Zer: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AZ. All other authors have declared no conflicts of interest.
405O - Neutrophil-lymphocyte and platelet-lymphocyte ratios as robust prognostic markers in sarcomas: A population-based analysis of 3746 sarcoma patients from Hong Kong
- Sui Chun Sampson Kwan
- Sui Chun Sampson Kwan
- Carlos K. Wong
- CW Ho
- Ying Zhun Zhang
- Teresa Tse
- Yat-ming Lau
- Linda K. Leung
- Teresa Tan
- Herbert Loong
Abstract
Background
Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to be prognostic in various cancers. Prior reports of this in sarcomas have predominantly been made through smaller cohorts from single institutions. We investigated the prognostic implications of these indices in patients with soft-tissue (STS) and bone sarcomas using a large population-based database.
Methods
A population-based retrospective database was assembled to extract pts with sarcoma, as defined as ICD-9-CM codes of bone (170.x) or/and soft tissue (171.x) who have attended clinics or hospitals of the Hong Kong Hospital Authority between Jan 2004 and Mar 2018. Eligible patients (pts) with index presentation of bone sarcoma or/and STS on or after Jan 2005 were analysed to allow 1-year window. The most recent documented lymphocyte, neutrophil, and platelet counts from the index date of sarcoma diagnosis were retrieved, and the neutrophil-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were correlated with survival. Abnormal (abn) NLR and abn PLR are defined as NLR≥2.5 and PLR≥182 respectively. Restricted cubic spline plots were used to explore the shape of association between baseline NLR and PLR and all-cause mortality, fitting a restricted cubic spline function with four knots (5th, 35th, 65th, and 95th centiles).
Results
Of 3746 pts identified, 3358 pts satisfied eligibility: bone n = 661, STS n = 2576, both n = 121. NLR and PLR is available for 89.93% (n = 3020) of eligible pts, amongst which 65.9% (n = 1989) had abn NLR while 47.6% (n = 1438) had abn PLR., Abn NLR and abn PLR are each associated with higher all-cause mortality (abn NLR: HR 1.698, p < 0.001, 95% CI 1.424-2.025; abn PLR: HR 1.346, p < 0.001, 95%CI 1.164-1.555) and cancer-related mortality (abn NLR: HR 1.648, p < 0.001, 95% CI 1.341-2.024; abn PLR: HR 1.430, p < 0.001, 95% CI 1.205-1.697).
Conclusions
This is the largest assembled population-based sarcoma cohort in Asia. We show that NLR and PLR are robust prognostic factors, and abn NLR and PLR have negative effects on survival. More importantly, the relationship between NLR and PLR and mortality is shown to be non-linear.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
406O - VEGFR2 Polymorphisms as Novel Biomarker of Anti-angiogenic Therapy for Pediatric and Young Adult Sarcoma
- Qiyuan Bao
- Qiyuan Bao
- Yuehao Hu
- Junxiang Wen
- Yuhui Shen
- Weibin Zhang
Abstract
Background
The impact of germline mutations of the angiogenesis pathways on the therapeutic response has been extensively studied for the carcinoma population. However, such information is almost unknown for pediatric and young adult’s sarcoma, for which the field has seen the rapid growing popularity of the use of the anti-angiogenic therapy.
Methods
In this study, we retrospectively analyzed 79 tissue sarcoma patients less than 45 yrs receiving anti-angiogenic therapy (apatinib). In 67 (84%) of these patients, twenty previously reported single nuclear polymorphism (SNPs) in angiogenesis pathway were genotyped to screen for potential toxicity and predictive biomarkers.
Results
The mean 6 mo PFS rate was 64%, with the duration of response varying from no response to more than 26 months. Multivariate analysis indicated that hand-foot reactions, hair depigmentation and spontaneously pneumothorax (SP) remain independent toxicity biomarker for greater PFS. Interestingly, we observed a strong correlation of ITGA2 rs1126643 polymorphism vs surgical wound complications (C/C 4% vs C/T 24% vs T/T 33%, p = 0.008) as well as SP (C/C 13.8% vs C/T 36.4% vs T/T 66%), suggesting that Integrin mechanism might underline both toxicities. Moreover, VEGFR2 rs2071559 polymorphism remains the only sensitivity biomarker for mPFS (mutation vs WT, 12 mo vs 5 mo), regardless of the sarcoma subtypes. Surprisingly, such mutations were to be associated with the incidence of hair depigmentation (R = 0.398, p = 0.026), further supporting that hair discoloration is a mechanism-based toxicity biomarker. Moreover, a significant higher frequecies of such two mutations (0.53 for ITGA polymorphism, 0.59 for VEGFR2 polymorphism) in our cohort than general Han Chinese (1000G project database) suggest a theoretical impact on the sarcomagenesis.
Conclusions
Our study is the first one examining the angiogenesis germline polymorphism for the younger population in bone and soft tissue cancer. VEGFR2 (rs2071559) as well as ITGA (rs1126643) might serve as pan-sarcoma biomarkers for VEGFR2 targeted therapy and warrant further validation for its biological and clinical implications.
Legal entity responsible for the study
Ruijin Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Discussion led by moderators
- Tom Wei-Wu Chen
- Silvia Stacchiotti
- Aisha Miah
- Tom Wei-Wu Chen
- Silvia Stacchiotti
- Aisha Miah