Oral abstracts:
Efficacy and safety of elinzanetant for vasomotor symptoms associated with adjuvant endocrine therapy: Phase 3 OASIS 4 trial
Vasomotor symptoms (VMS) associated with adjuvant endocrine therapy (AET) impact quality of life and decrease treatment adherence, worsening breast cancer outcomes. There are few effective treatment options and none approved for this indication. (Prof Donal Brennan, right)
Prognostic significance of PSA>0.2 after 6-12 months treatment for metastatic hormone-sensitive prostate cancer (mHSPC) intensified by androgen-receptor pathway inhibitors (ARPI): A multinational real-world analysis of the IRONMAN registry
Phase III post-hoc analyses show poor prognosis of PSA >0.2 in mHSPC treated by androgen deprivation therapy (ADT) and ARPI, but it remains unclear 1) when PSA cutoffs should be interpreted for prognostic significance, and 2) how PSA cutoffs may differ in real-world multinational data. IRONMAN (International Registry for Men with Advanced Prostate Cancer) prospectively enrolled mHSPC patients from 16 countries and is a unique large data set to investigate these questions. (Prof Ray McDermott, right, co-author)
Who’s on the podium? Geographic and career diversity of ASCO Annual Meeting presenters
The ASCO annual meeting is the world’s preeminent meeting of oncology professionals. Giving an oral presentation at the ASCO annual meeting is a landmark in a career. We examined the training and geographic diversity of presenters. (Dr Niamh Coleman, co-author)
Gene-specific outcomes in patients with Lynch syndrome treated by immune checkpoint blockade for advanced cancer
Lynch syndrome (LS), caused by germline pathogenic variants (gPVs) in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2), is characterized by microsatellite instability (MSI)/mismatch repair deficiency (MMRd) of associated tumors. The impact of the underlying gPV on the prognosis of LS patients with advanced cancer receiving ICB has not been elucidated. (Dr Emily Harrold, co-author)
Association of immunotherapy of high-risk neuroblastoma patients with long term infusion of dinutuximab beta with survival over short term infusion: Results from the HR-NBL1/SIOPEN trial
Dinutuximab beta (DB) delivered as long-term infusion is associated with a lower frequency and magnitude of side effects compared to short-term infusion (STI). Here, we evaluated the efficacy (event free survival- and cumulative incidence of relapse-rates at 5 years) of LTI compared to STI within the HR-NBL1/SIOPEN trial (EudraCT:2006-001489-17).. (Co-author, Dr Cormac Owens, right)
Posters:
Impact of elinzanetant on sleep disturbances and quality of life in women undergoing adjuvant endocrine therapy for breast cancer: Phase 3 OASIS 4 trial
Vasomotor symptoms (VMS) and sleep disturbances are common in women taking adjuvant endocrine therapy (AET) for hormone receptor-positive (HR+) breast cancer and can impact quality of life and treatment adherence, potentially affecting breast cancer outcomes. There are few efficacious treatments and none approved in this indication. Elinzanetant (EZN) is a dual neurokinin-1 and -3 receptor antagonist in development for the treatment of VMS. (Prof Donal Brennan, right)
Sexual health communication and young-onset cancer (YOC): Healthcare practitioners’ attitudes and practices
Sexual health-related discussions are often challenging for Healthcare Practitioners (HCPs) and patients, making sexual health communication a frequently neglected aspect of cancer care. HCPs’ lack of knowledge regarding LGBTQ+ cancer care contributes to greater unmet survivorship needs. We explored HCPs’ attitudes and practices regarding sexual health-related discussions with YOC patients (25yrs–50yrs) to identify barriers and training needs for improving effective communication. (Pictured right: Author Louise Kelly, Co-author Prof Maeve Lowery)
Molecular and clinical determinants of targeted therapy (TT) outcomes in biliary tract cancer (BTC): Analysis of a prospectively maintained next generation sequencing (NGS) biorepository
BTCs are genomically diverse. TT have established antitumor activity in a subset of pts that harbour actionable alterations; however, most patients (pts) do not respond to or experience acquired resistance on TT. We sought to explore genomic mechanisms of response across the spectrum of BTCs. (Dr Darren Cowzer, right)
Cost and resource utilisation for liquid biopsy vs tissue biopsy genotyping in advanced NSCLC: A micro-costing model
For patients with advanced non-small cell lung cancer, tumour genotyping identifies actionable variants that inform targeted therapeutic choices, that improve outcomes. Liquid biopsy genotyping (LBG) is a non-invasive approach to tissue biopsy genotyping (TBG) that reduces turnaround, avoids repeat tissue biopsy, and can identify additional actionable variants. However, despite these benefits, patient access to LBG is not universal in a range of healthcare systems. While others have developed models evaluating the cost-effectiveness of LBG, these have are limited by assumptions regarding frequency of oncogenic variants and treatment utilisation. We utilised a micro-costing model (MCM) to quantify the cost/resources of LBG and TBG in a prospective trial (PLAN; ClinicalTrials.gov Identifier: NCT05542485) aimed at investigating the feasibility of LBG in a tertiary cancer centre. (Author Dr David O’Reilly, right)
8-year outcomes of enzalutamide (ENZA) versus a non-steroidal anti-androgen (NSAA) for metastatic, hormone-sensitive prostate cancer (ENZAMET; ANZUP 1304)
We previously reported that ENZA improved overall survival (OS) after median follow-up times of 34 and 68 months, in comparison with a NSAA, when added to testosterone suppression, with or without concurrent early docetaxel, for mHSPC. We now report outcomes after median follow-up of 98 months. (Prof Ray McDermott, Prof John McCaffrey, right)
Rapid analysis and response evaluation of combination anti-neoplastic agents in rare tumors (RARE CANCER) trial: RARE 2 talazoparib and temozolomide
Preclinical data generated from NIH/NCI Patient-Derived Models Repository (PDMR) demonstrated significant synergistic activity of talazoparib (a PARP inhibitor) combined with temozolomide (an alkylating agent) in patient-derived xenograft models of rare adult and pediatric cancers. This clinical trial aimed to evaluate the objective response (OR) rate of this combination in patients with advanced rare cancers in exploratory fashion. Correlatives include genomic and transcriptomic profiling of tumor tissue, circulating tumor DNA (ctDNA), circulating tumor cells, and assessments of apoptosis and epithelial-mesenchymal transition in relation to treatment activity. (Co-author, Dr Geraldine O’Sullivan-Coyne, right)
KEYNOTE-859: 4.5-year median follow-up of pembrolizumab plus chemotherapy for previously untreated advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma
In the phase 3 KEYNOTE-859 study (NCT03675737), first-line pembrolizumab (pembro) + chemotherapy (chemo) continued to provide longer OS (HR, 0.79; 95% CI, 0.71-0.88) and PFS (HR, 0.76; 95% CI, 0.68-0.85), and a higher ORR (51.0% vs 42.0%) vs placebo + chemo in participants (pts) with HER2-negative G/GEJ adenocarcinoma, after a median follow-up of 41.6 mo (August 22, 2023). We present results after an additional 13 mo of follow-up. (Co-author, Prof Maeve Lowery, right)
A randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3
The addition of antiangiogenic agents to standard first-line treatment with a programmed cell death protein 1 (PD-1) inhibitor and platinum doublet chemotherapy has shown efficacy in patients with metastatic non–small cell lung cancer (NSCLC). Ivonescimab is a novel tetravalent bispecific antibody that targets PD-1 and vascular endothelial growth factor. In a phase 2 trial, ivonescimab plus chemotherapy showed objective response rates (ORRs) of 71.4% and 54.2% and median progression-free survival (PFS) of 11.1 and 13.3 months in patients with metastatic squamous (SQ) and nonsquamous (NSQ) NSCLC, respectively (1). (Co-author, Prof Jarushka Naidoo, right)
Association of circulating immune and metabolic markers with clinical outcomes in the ENZAMET trial (ANZUP 1304)
ENZAMET showed that enzalutamide (ENZ) significantly improves overall survival (OS) of metastatic hormone-sensitive prostate cancer (mHSPC) compared to conventional non-steroidal anti-androgen (NSAA). However, intrinsic and acquired resistance to ENZ are ongoing problems. In the CHAARTED mHSPC cohort, elevated circulating IL8 and IGFBP1, and a low IGF1:IGFBP1 ratio, were associated with shorter OS and shorter time to castration-resistance. The aim of this study was to confirm the prognostic association of IL8, IGFBP1, and IGF1:IGFBP1 in mHSPC, and also explore the relationship of a set of immune markers with ENZ treatment by post-hoc analysis of ENZAMET. (Co-author, Prof Ray McDermott, right)
Picking needles in a haystack: Exploring rare variants of a pan-cancer target in the RET landscape from 229,453 adult cancer patients
Advances in precision oncology have led to the approval of tumor-agnostic therapies, and RET, due to its role as a driver of oncogenesis across multiple tumor types, is increasingly recognized as a pan-cancer target. RET alterations, including mutations and fusions, are relatively rare events, however, potent and selective RET inhibitors such as selpercatinib and pralsetinib have demonstrated remarkable efficacy and changed clinical practice in RET-driven NSCLC, thyroid cancer and other cancers. Here, we present a comprehensive analysis of RET alterations in pan-cancer adult malignancies. (Author Dr Niamh Coleman, right)
EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA)
(Neo)adjuvant systemic treatment, with chemotherapy and/or endocrine therapy (ET), substantially reduces the recurrence rates of estrogen receptor positive (ER+) human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer (BC). However, recurrences still occur up to 20 years after diagnosis. Circulating tumor DNA (ctDNA) has emerged as a useful biomarker for surveillance in several solid tumors. ctDNA-based detection of molecular recurrence could allow the start of effective therapies before the clinical evidence of metastases. Elacestrant, a selective ER degrader, approved in the advanced setting of ER+/HER2- ESR1-mutated BC following progression on a CDK4/6-inhibitor, could be used at the time of ctDNA-based molecular relapse to delay or prevent the clinical manifestation of distant metastasis. (Co-author, Prof Catherine Kelly, right)
Clinico-genomic characterization of PALB2-mutated pancreatic adenocarcinoma
Pancreatic adenocarcinoma (PDAC) with germline (g) or somatic (s) mutations in BRCA1/2 and PALB2 exhibit unique molecular characteristics and predict response to platinum-based chemotherapy and PARP inhibition. However, distinct features of PALB2 and PDAC are not well described. Herein, we characterize distinct clinico-genomic features of patients (pts) with g/s PALB2 and PDAC. (Co-author, Dr Emily Harrold, right)
Efficacy and safety of larotrectinib in patients with TRK fusion thyroid carcinoma: An updated analysis
NTRK gene fusions are oncogenic drivers in various tumor types, including thyroid carcinoma (TC). Larotrectinib (laro) is the first-in-class, highly selective, central nervous system-active TRK inhibitor, approved for tumor‑agnostic use in patients (pts) with TRK fusion cancer. Here, we report updated long-term efficacy and safety data in pts with TRK fusion TC treated with laro. (Co-author, Prof Ray McDermott, right)
Larotrectinib resistance in TRK fusion cancers: Analysis of a tumor-agnostic, global clinical trial dataset
Larotrectinib (laro) is the first-in-class, highly selective, TRK inhibitor approved for tumor- and age-agnostic use in TRK fusion cancers. This is the seminal report of primary and secondary laro resistance based on an analysis of the regulatory dataset that supported drug approval across multiple countries. (Co-author, Prof Ray McDermott, right)
Publication:
Investigation of clonal hematopoiesis frequency following PARP inhibitor treatment and its association with prior platinum therapy exposure
Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a critical part of treatment for multiple solid tumors, especially among patients with germline homologous recombination deficiency (HRD). With their significant impact on survival has come a concern for therapy-related myeloid neoplasms (tMN). DNA damage response (DDR) mutations causing clonal hematopoiesis (CH) are the driving force behind the tMNs. We hypothesized that platinum and PARPi therapy have significant variation in their impact on CH, further altered by the presence of HRD. (Co-author, Prof Karen Cadoo, right)
Incidence of colorectal cancer in the republic of Ireland: Trends and challenges
The incidence of early onset colorectal cancer (EOCRC; ≤50 years) is increasing globally, while the incidence of average onset colorectal cancer (AOCRC; colorectal cancer ≥ 50years) is stabilising and beginning to decline with increased screening uptake. In Ireland screening begins at 59 years. We analysed trends in incidence of colorectal cancer (CRC) in the Republic of Ireland over a twenty-eight year period. (Pictured right: Co-authors Prof Ray McDermott & Prof Grainne O’Kane)
“How much does your medication cost?”: Assessing patient attitudes towards the costs of oncology medication to society
Global oncology medication expenditure has increased rapidly in recent decades. In many countries, this cost is borne by the healthcare system rather than individual patients. Minimal research has investigated patient attitudes towards the societal costs of these medications. Our aims were to describe patient attitudes towards the societal costs of oncology medications and their desires to be better informed of these costs. (Pictured right: Co-author Prof Seamus O’Reilly)
Awards:
Young Investigator Awards
First awarded in 1984, the YIA provides research funding to promising young physicians during the final years of training to support the transition to a faculty appointment and to encourage quality research in clinical oncology. (Dr David O’Reilly, right)