Sessions are scheduled in Singapore Time (SGT)
- Sheng-Po Hao (Taipei City, Taiwan)
- Ana Martins Ferreira Varges Gomes (Faro, Portugal)
220O - RATIONALE-309: Effects of tislelizumab on health-related quality of life (HRQoL) in patients with recurrent or metastatic nasopharyngeal cancer (R/M NPC)
- Yunpeng Yang (Guangzhou, China)
Abstract
Background
In RATIONALE-309 (NCT03924986), tislelizumab with gemcitabine and cisplatin (GP) improved progression-free survival, objective response rate, and duration of response compared to placebo +GP in patients receiving first-line treatment for R/M NPC. This study evaluated HRQoL in the intent-to-treat (ITT) population and post-hoc analysis examined HRQoL in patients with liver metastases (LM) subgroup, a negative prognostic factor of overall and cancer-specific survival in patients with NPC.
Methods
Eligible patients in this double-blind, Phase 3 study were randomized 1:1 to tislelizumab +GP (Arm A) or placebo +GP (Arm B). HRQoL was evaluated using EORTC QLQ-C30 and QLQ Head and Neck Cancer module (H&N35). Mean changes from baseline to cycles 4 and 8 were estimated based on linear mixed effects model for repeated measures. Time to deterioration (TTD) was compared between treatment arms using a stratified Cox proportional hazard model. Nominal p-values are reported for descriptive purposes.
Results
All 263 randomized patients (Arm A n=131, Arm B n=132) comprised the ITT population; 43% of them (Arm A n=56; Arm B n=57) were diagnosed with LM. No differences in change from baseline to cycle 4 between the arms were observed for the ITT patients or LM subgroup. Greater reduction from baseline to cycle 8 were observed in Arm A vs Arm B in QLQ-H&N35 pain score (-2.82 vs -0.45, p=0.0117 for ITT population; -3.85 vs -0.05, p=0.0092 for LM subgroup) and sense score (-2.86 vs -0.01 for ITT population; -6.16 vs 1.03, p=0.0338 for LM subgroup). Greater improvement at cycle 8 in Arm A in QLQ-H&N35 symptoms index score (-3.62 vs -1.40, p=0.0580) and restrictions in speech (-2.43 vs 0.41, p=0.0694) for LM subgroup were observed. Differences in TTD were not observed.
Conclusions
Patients treated with tislelizumab +GP had greater improvements in symptoms than patients treated with placebo +GP. LM patients experienced a greater reduction in overall symptoms, pain, and problems associated with senses. These results, along with improved survival and an acceptable safety profile, suggest tislelizumab +GP represents a potential first-line treatment option for patients with R/M NPC.
Clinical trial identification
NCT03924986.
Editorial acknowledgement
Writer: Jason C. Allaire, Generativity.
Legal entity responsible for the study
BeiGene Ltd.
Funding
BeiGene Ltd.
Disclosure
Y. Wu, S. Leaw, F. Bai, Y. Wang, B. Tang: Financial Interests, Personal, Full or part-time Employment: BeiGene. N. Zhao: Financial Interests, Personal, Invited Speaker: BeiGene. G. Barnes: Non-Financial Interests, Institutional, Full or part-time Employment: BeiGene Ltd. All other authors have declared no conflicts of interest.
221O - Induction chemotherapy regimen of docetaxel plus cisplatin vs docetaxel, cisplatin plus fluorouracil followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Preliminary results of a phase III multicenter randomized controlled trial
- SHASHA HE (Guangzhou, China)
Abstract
Background
Induction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen.
Methods
We performed an open-label, noninferiority, phase 3, multicenter, randomized, controlled trial at six centers in China. Eligible NPC patients were randomly assigned (1:1) to receive either TP or TPF followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority of TP in failure-free survival.
Results
Between June 2018 and October 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% in the TP group and 82·4% in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (P = 0·001), grade 1 or 2 diarrhea (P = 0·032), and grade 3 or 4 neutropenia (P = 0·014) in the induction chemotherapy period.
Conclusions
The preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
222O - Updated efficacy and safety of larotrectinib in patients with TRK fusion salivary gland tumours
- Lin Shen (Beijing, China)
Abstract
Background
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers of various tumour types, including salivary gland tumours (SGTs). Secretory carcinoma of the salivary gland, a rare subset of SGTs, is characterised by an ETV6-NTRK3 gene fusion found in ≥80% of cases. Larotrectinib is a highly selective, central nervous system-active, tropomyosin receptor kinase (TRK) inhibitor with an objective response rate (ORR) of 92% across 24 evaluable patients (pts) with a variety of SGTs, as of July 2020 (Le et al. Oncologist 2022 [in press]). We report updated efficacy and safety of larotrectinib in pts with TRK fusion SGTs with longer follow-up.
Methods
Pts with TRK fusion SGTs were identified from two larotrectinib clinical trials (NCT02122913, NCT02576431). Pts received larotrectinib 100 mg twice a day (BID) except for one pt who received 150 mg BID in the phase 1 trial (NCT02122913). Response was assessed by independent review committee (per Response Evaluation Criteria in Solid Tumours v1.1).
Results
As of July 2021, 25 pts with TRK fusion SGTs were identified, including 24 with an additional year of follow-up. Median age was 59.0 years (range 28–80). All pts had ETV6-NTRK3 gene fusions. ORR was 84% (95% CI 64–95%): 8 complete responses, 13 partial responses, 2 stable disease and 2 progressive disease. Median time to response was 1.8 months. Median duration of response (DoR) was not reached; median follow-up was 39.6 months. Median progression-free survival (PFS) was 56.0 months (95% CI 30.8–not estimable) at a median follow-up of 41.3 months. Median overall survival (OS) was not reached at a median follow-up of 43.7 months. The 36-month DoR, PFS, and OS rates were 71%, 64%, and 82%. Duration of treatment ranged from 1.0 to 68.0 months. At data cut-off, 8 pts had progressed, with 5 pts continuing treatment post-progression for ≥4 weeks. Treatment-related adverse events (TRAEs) were mostly Grade 1–2. Grade 3–4 TRAEs were reported in 6 pts (24%). There were no treatment discontinuations due to TRAEs.
Conclusions
Larotrectinib demonstrated rapid and durable efficacy with a favourable safety profile in pts with TRK fusion SGTs. These data highlight the importance of identifying NTRK gene fusions in pts with SGTs.
Clinical trial identification
NCT02122913, NCT02576431.
Editorial acknowledgement
Medical writing assistance was provided by Anastasija Pesevska, PharmD, of Scion Medica, London, UK.
Legal entity responsible for the study
Bayer HealthCare Pharmaceuticals, Inc.
Funding
These studies were funded by Bayer HealthCare Pharmaceuticals, Inc. and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.
Disclosure
L. Shen: Financial Interests, Institutional, Research Grant: Beijing Xiantong Biomedical Technology Co., Ltd., Qilu Pharmaceutical Co., Ltd., Zaiding Pharmaceutical (Shanghai) Co., Ltd., Yaojie Ankang (Nanjing) Technology Co., Ltd., Baiji Shenzhou (Beijing) Biotechnology Co., Ltd.; Financial Interests, Personal, Advisory Role: MSD, BMS, Merck, AstraZeneca, Daiichi Sankyo, Roche, Minji biopharmaceutical, Harbour BioMed; Financial Interests, Personal, Speaker’s Bureau: Hutchison Whampoa, MSD. D.S. Hong: Financial Interests, Personal, Other, Travel, accommodations, expenses: AACR, ASCO, Bayer, Genmab, Gilead, SITC, Telperian; Financial Interests, Personal, Other, Consulting, Speaker, or Advisory Role: AbbVie, Adaptimmune, Alpha Insights, Acuta, Alkermes, Amgen, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, COR2ed, COG, Cowen, Ecor1, Gennao Bio, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, Immunogen, Infinity, Janssen, Liberium, MedaCorp, Medscape, Numab, Oncologia Brasil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, RAIN, SeaGen, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point Therapeutics, WebMD, YingLing Pharma, Ziopharm; Financial Interests, Personal, Ownership Interest, Advisor: Molecular Match; Financial Interests, Personal, Ownership Interest, Founder, Advisor: OncoResponse, Telperian; Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Adlai-Nortye, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Erasca, F. Hoffmann-LaRoche, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa Kirin, Loxo, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, TCR2, Teckro, Turning Point Therapeutics, VM Oncology. M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono pharma, Bristol Myers Squibb, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol Myers Squibb, Loxo, GlaxoSmithKline, Lilly, Rakuten Medical; Financial Interests, Institutional, Research Grant: Bayer. C.S. Baik: Financial Interests, Personal, Other, External consultant: AstraZeneca; Financial Interests, Personal, Other, External Consultant: Blueprint Medicines, Daiichi, Takeda, TurningPoint Therapeutics, Guardant Health, Regeneron, Silverback Therapeutics; Financial Interests, Institutional, Research Grant: Loxo, AstraZeneca, Pfizer, Spectrum Phaemaceuticals, Blueprint Medicines, Daiichi Sankyo, Rain Therapeutics, Abbive, TP Therapeutics, Lilly Oncology, Janssen. J.R. Bauman: Financial Interests, Personal, Advisory Board: Kura, Janssen, Pfizer, Blueprint Medicine, Lilly, Merck, Mirati, Turning Point Therapeutics, BeiGene. J. Gilbert: Financial Interests, Personal, Advisory Board: Exelixis, Loxo, HRA Pharma, Bayer, Cue; Financial Interests, Personal, Other, Editor of fellowship magazine: OncLive; Financial Interests, Institutional, Invited Speaker, Money to institution to run trial: Pfizer, Exelixis; Non-Financial Interests, Personal, Invited Speaker, Local affiliate of ASCO: Tennessee Oncology Practice Society. M.S. Brose: Financial Interests, Institutional, Research Grant: Bayer, Loxo Oncology, Genentech, Eisai, Blueprint Medicines, Lilly, Novartis; Financial Interests, Personal, Advisory Role: Bayer, Loxo Oncology, Genentech, AstraZeneca, Lilly; Financial Interests, Personal, Other, Honoraria: Clinical Care Options, Medscape, OncLive, PeerView. J.E. Grilley-Olson: Financial Interests, Personal, Other, Consulting/honoraria: SpringWorks, Sorrento. T. Patil: Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, PRIME Oncology, Aptitude Health, LLC; Financial Interests, Personal, Other, Consultancy fees: Guidepoint, Axiom. R.S. McDermott: Financial Interests, Personal, Advisory Board: Pfizer, Amgen, BMS, Bayer, Janssen, Clovis; Financial Interests, Personal, Invited Speaker: MSD, Ipsen, Astellas; Financial Interests, Institutional, Invited Speaker: MSD, Clovis, BMS, Regeneron, Bayer, Astellas. L.E. Raez: Financial Interests, Personal, Research Grant: LOXO, BMS, Pfizer, AstraZeneca, Syndax, Mirati, Nanth Health, Liquid Genomics, Guardant Health, Lilly Oncology, Merck. J.M. Johnson: Financial Interests, Personal, Research Grant: BMS, AstraZeneca, Merck; Financial Interests, Personal, Other, Consulting: Foundation Medicine, Rakuten. R. Norenberg, L. Dima, C.E. Mussi: Financial Interests, Personal, Full or part-time Employment: Bayer. X. Le: Financial Interests, Personal, Other, Consulting/advisory fees: EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceutics, Boehringer Ingelheim, AbbVie, Novartis, Janssen, Hengrui Therapeutics, Daiichi Sankyo, Eli Lilly; Financial Interests, Institutional, Research Grant: Eli Lilly, Boehringer Ingelheim. A. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem Oncology, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Amgen, Janssen; Financial Interests, Personal, Other, CME: Medscape, Onclive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options; Financial Interests, Personal, Other, CME, Consulting: Axis; Financial Interests, Personal, Other, Consulting: Nuvalent, Merus, mBrace, EPG Health, Harborside Nexus, Ology, TouchIME, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Remedica Ltd., RV More; Financial Interests, Personal, Stocks/Shares: Treeline Biosciences; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Funding, Research funding: Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; Financial Interests, Personal, Funding, Research: Foundation Medicine; Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus; Other, Personal, Other, Other: Boehringer Ingelheim.
Invited Discussant 220O, 221O and 222O
- Ana Martins Ferreira Varges Gomes (Faro, Portugal)
Q&A and discussion
- Sheng-Po Hao (Taipei City, Taiwan)
223O - Exosomal miRNA and mRNA signatures as biomarker for head and neck cancer
- Linda Hofmann (Ulm, Germany)
Abstract
Background
Head and neck squamous cell carcinomas (HNSCC) are highly immunosuppressive. Exosomes are small extracellular vesicles that mediate intercellular communication. HNSCC patient’s plasma is enriched in immunomodulatory exosomes which correlate with clinical parameters. We investigate the miRNA and mRNA signatures of plasma-derived exosomes as potential biomarkers for HNSCC.
Methods
Exosomes were isolated from plasma of 16 HNSCC patients and 12 healthy donors (HD) by ultrafiltration and differential (ultra)centrifugation (EV-Track ID 210344). Primary tumor cells were obtained from the same HNSCC patients. Total exosomal and tumor RNA was used for targeted profiling of 798 miRNAs and 730 mRNAs. Differential presence and discriminatory potential of exosomal RNAs between HNSCC and HD were analyzed by multiple Mann-Whitney test and unsupervised hierarchical clustering. Ingenuity pathway analysis was applied to predict downstream effects of miRNAs and identify related pathways.
Results
Of all detected exosomal RNAs, 55% miRNAs and 31% mRNAs were HNSCC-exclusive, while 8% miRNAs and 48% mRNAs were HD-exclusive. 91 miRNAs and 347 mRNAs were significantly differentially present between HNSCC and HD exosomes. Both exosomal RNA signatures could successfully assign samples to “Tumor” or “Healthy”. 165 miRNAs and 146 mRNAs overlapped between corresponding tumor and exosomes and were considered as tumor-originating RNAs. These were filtered to 23 miRNAs inversely targeting 17 mRNAs, e.g. upregulated miR-421-3p targeting downregulated, anti-tumor IL15. Identified core hubs of tumor-originating RNAs were related to TLR, NF-κB and IFN signaling.
Conclusions
Exosomal miRNA and mRNA signatures have high discriminatory potential between HNSCC patients and HD. Final RNA candidates are currently validated in an independent cohort. Identified RNAs were related to pathways of immune regulation, inflammatory response and cellular development which highlights their relevance for disease pathogenesis.
Legal entity responsible for the study
The authors.
Funding
German Research Foundation.
Disclosure
All authors have declared no conflicts of interest.
224O - Survival differences between EU and Asia for head and neck cancer: Results of the RARECAREnet-Asia collaboration
- Annalisa Trama (Milan, Italy)
Abstract
Background
The epidemiology of head and neck cancer (HNC) differs between East Asia and Europe: some HNCs are common and have better survival in East Asia than in Europe. We analyzed the impact of sex, age, HNC subsite and histologies on survival differences between Europe and Asia leveraging the RARECAREnet-Asia collaboration between European and Asian population-based cancer registries (PBCR).
Methods
We analysed all HNCs: oral cavity, hypopharynx, larynx, nasal cavity, salivary gland, nasopharynx, oropharynx. Oropharynx subsites were grouped in tonsil and non-tonsil related. Nasopharyngeal tumours were differentiated in keratinising and non-keratinising. European data were provided by 94 PBCR (diagnosis period 2000-2007; follow-up 2008). Asian data were provided by the Taiwan and Japan PBCR (diagnosis period 2009-2011, follow-up 2016). Relative survival was modelled with a generalised linear model providing relative excess risks of death after adjusting for sex, age, subsite and histological grouping. Analyses were performed using federated learning which enables analyses without sharing sensitive data.
Results
HNC subsites and histologies distribution and survival differed between the 3 countries. Compared to Europe, after adjusting for covariates, we confirmed better survival in Taiwan and in Japan for each HNC.
Conclusions
The lower survival in Europe was attributed to different period of diagnosis (in Europe intensity modulated radiotherapy was not yet standard), more advanced stage at diagnosis and worse treatment outcome. Our data confirm the need of international collaboration to improve early diagnosis and treatment appropriateness for HNC. RARECAREnet-Asia was established in the framework of Rare Cancers Asia to build a bridge between Asia and Europe to learn from each other in addressing the challenges in the respective continents faced by rare cancers considering the different cancer epidemiology. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing between organisations and geographies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 223O and 224O
- Naomi Kiyota (Kobe, Hyogo, Japan)
Q&A and discussion
- Sheng-Po Hao (Taipei City, Taiwan)