Rachel Wong

BackgroundThis study explores the potential benefits of neoadjuvant chemotherapy in borderline resectable (BR) pancreatic adenocarcinoma. Despite neoadjuvant treatment (NAT) increasingly being utilised, uncertainty remains as to the optimal approach.Patients and methodsThis study assessed clinical outcomes for 218 consecutive BR patients from the PURPLE registry. We compared initial surgery (IS) to NAT overall, and between different chemotherapy regimens.ResultsOf 1314 non-metastatic patients enrolled, 218 (17%) were considered BR. Of 28 planned for IS, 11/28 (39%) had their tumour excised compared to 68/152 (45%) with NAT (P = 0.59). Among those who received NAT and were resected, 52/100 (52%) received FOLFIRINOX (P = 0.234) and 8/28 (29%) received nab-paclitaxel with gemcitabine (nabPGem). There was no difference in median overall survival (OS) [hazard ratio (HR) 0.72, P = 0 …

12Background: Adjuvant chemotherapy (CT) following neoadjuvant chemoradiation and surgery for locally advanced rectal cancer (LARC) is widely adopted, despite uncertain survival benefit. Circulating tumor DNA (ctDNA) detection after surgery has been shown to be a strong prognostic marker in localized colorectal cancer and potentially could inform adjuvant treatment decision making. Methods: AGITG DYNAMIC-Rectal is a multi-centre randomized controlled phase II trial. Eligible patients (pts) had LARC (cT3-4 and/or cN+) treated with neoadjuvant chemoradiation, total mesorectal excision, and were fit for adjuvant CT. Pts were randomly assigned 2:1 to ctDNA-guided management or standard management (clinician decision). A tumor-informed personalized ctDNA assay was used. For the ctDNA-guided group, a positive result at 4 and/or 7 weeks after surgery prompted 4 months of oxaliplatin-based or …

BackgroundA substantial proportion of patients with stage III colorectal cancer (CRC) are older than 70 years. Optimal adjuvant chemotherapy (AC) for older patients (OP) continues to be debated, with subgroup analyses of randomized trials not demonstrating a survival benefit from the addition of oxaliplatin to a fluoropyrimidine backbone.Patients and MethodsWe analyzed the multisite Australian ACCORD registry, which prospectively collects patient, tumor and treatment data along with long term clinical follow-up. We compared OP (≥70) with stage III CRC to younger patients ([YP] <70), including the proportion recommended AC and any reasons for not prescribing AC. AC administration, regimen choice, completion rates, and survival outcomes were also examined.ResultsOne thousand five hundred twelve patients enrolled in the ACCORD registry from 2005 to 2018 were included. Median follow-up was 57.0 …

BackgroundPancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting.MethodsA prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old).ResultsOf 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative …

BackgroundPD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.MethodsKEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every …

BackgroundLong course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) results in a complete pathological CR in 10-30% of patients (pts). Radiotherapy (RT) is immuno-stimulatory by enhancing tumour cell death, but also immunosuppressive stimulating PDL1 production and myeloid-derived suppressor cells. PDL1 inhibition may be required to enhance RT immuno-stimulatory effects. Hypothesis: In pts with resectable LARC, Avelumab given post LCCRT may enhance tumour response rates whilst reducing relapses.MethodsPhase II single arm trial. Pts had LCCRT (50.4 Gy+ 5FU [225mg/m 2/day/CI] or Capecitabine [825mg/m 2 BID]/5.5 weeks). Post LCCRT pts received 4 cycles Avelumab (AV)(10mg/kg, q2 weeks), then resection 10-12 weeks post LCCRT. Fresh tumour biopsy/ctDNA sampling taken at pre LCCRT, pre AV and at surgery. Response by FDG PET and pelvic MRI. Inclusion …

Background Treatment with cetuximab provides a survival benefit for patients with RAS wild‐type metastatic colorectal cancer (mCRC). Practice‐defining cetuximab studies utilised weekly (q1w) administration. More convenient second weekly (q2w) administration is supported by pharmacokinetic data and a recent meta‐analysis, but large head‐to‐head studies have not been conducted. Therapeutic Goods Association (TGA) prescribing information states cetuximab be administered q1w for all indications. Aim To assess the real‐world use of q1w versus q2w cetuximab schedule and any difference in outcomes. Methods We analysed data from a prospective mCRC database at seven Melbourne hospitals from January 2010 to August 2019. Characteristics and outcomes for cetuximab‐treated patients were examined, comparing q1w versus q2w schedules. Progression‐free survival (PFS) and overall survival (OS …

3616Background: Neoadjuvant long course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) results in a complete pathological response rate in 10-30% of patients (pts), but with 20-40% non-responders and 10-15% have local recurrence. Radiotherapy (RT) is immuno-stimulatory by enhancing local/distant tumour cell death, but also immunosuppressive as it stimulates PDL1 production and myeloid-derived suppressor cell activity. Hence PDL1 inhibition may be required to enhance the immuno-stimulatory effects of RT. Hypothesis: In pts with resectable LARC, the anti-PDL1 antibody Avelumab given post LCCRT may enhance the pathological/imaging response rates whilst reducing local/distant relapse rates. Methods: Phase II single arm trial. All pts had standard LCCRT (50.4Gy RT plus 5FU [225mg/m2/day/CI] or Capecitabine [825mg/m2 BID on days of RT] over 5.5 weeks). Post LCCRT …

Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver …

Background The administration of adjuvant chemotherapy (AC) to colorectal cancer (CRC) patients in Australia and impact of recent trial data has not been well reported. We aim to evaluate temporal trends in AC treatment and outcomes in real‐world Australian patients. Methods CRC patients were analyzed from 13 hospitals, stratified by stage (II or III) and three 5‐year time periods (A: 2005–2009, B: 2010–2014, C: 2015–2019). Stage III was further stratified as pre‐ and post publication of the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration (March 2018). AC prescription, time‐to‐recurrence (TTR), and overall survival (OS) was compared across the time periods. Results Of 3977 identified patients, 1148 (stage II: 640, stage III: 508), 1525 (856 vs. 669), and 1304 (669 vs. 635) were diagnosed in Period A, B, and C, respectively. Fewer patients in Period C received AC compared to …

BackgroundFirst-line (1L) treatment options for LS RASwt mCRC include the addition of epidermal growth factor receptor inhibitors (EGFRi) to chemotherapy (CT), supported by the overall survival advantage versus CT+ bevacizumab (BEV) demonstrated recently in PARADIGM, the first phase 3 trial with pre-planned analysis by tumour side. Treatment selection and outcomes in Australasian routine practice has yet to be described.MethodsData from 1/2015–5/2023 on patients with LS RASwt mCRC who received 1L doublet CT for palliative intent was reviewed from TRACC, a prospective, multi-site Australasian registry. Baseline clinicopathological characteristics and survival outcomes were analysed with p≤ 0.05 denoted as statistical significance.ResultsOf 676 LS RASwt, palliative intent, mCRC patients, 573 (85%) were actively treated, 404 (60%) receiving 1L doublet CT. Of these, 193 (48%) also received …

Background Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable Method A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log‐rank model and Kaplan–Meier analysis. Results The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy …

Background and Aims: Cancer of unknown primary encompasses a diverse range of cancer types, whereby a metastatic lesion(s) is identified but a primary tumour evades clinical detection. Not all patients with cancer of unknown primary in Australia receive a standardised workup and this may lead to prolonged time to diagnosis and poor patient experience. This trial, titled Solving Unknown Primary Cancer - Earlier Diagnosis (SUPER-ED), aims to (1) standardise aModel of Care that adopts a standardised diagnostic workup adapted from the Optimal Care Pathways, with an embedded care coordinator, access to a virtual, national multidisciplinary meeting and an educational website and (2) implement this newModel of Care across a network of oncology services. This trial is funded from theMedical Research Future Fund. Method(s): This is a stepped-wedge cluster randomised trial comparing a control phase …

Background Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. Aims This analysis aims to explore real‐world treatment landscape of metastatic colorectal cancer in the third‐line setting. Methods We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression. Results Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third‐line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)‐oxaliplatin combination was the …

BackgroundThere is currently potential overuse of adjuvant chemotherapy (AC) in patients with stage II colon cancer (CC) given the uncertain survival benefit in unselected patients. A circulating tumour DNA (ctDNA) approach has the ability to improve patient selection for AC, defining patients who may benefit from treatment (ctDNA positive) and those who will not (ctDNA negative). This study aimed to estimate the health and economic impact of ctDNA-guided prescription of AC for stage II CC.MethodsA cost-utility analysis was performed comparing ctDNA-guided AC prescription for stage II CC to standard of care (SOC), where 22.6% of SOC patients received AC, all ctDNA-positive patients (8.7%) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC to reflect potential non-compliance. A state …

BackgroundFirst-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking.ObjectiveTo compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit.MethodsA retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken.FindingsFrom 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median …

Background Metastatic pancreatic ductal adenocarcinoma (mPDAC) is highly lethal. Combination chemotherapy regimens improve overall survival (OS). Historically, only one‐third of mPDAC patients in Victoria received chemotherapy. Aim To describe current Australian chemotherapy utilisation and outcomes in patients with mPDAC using the multi‐site PURPLE (Pancreatic cancer: Understanding Routine Practice and Lifting End Results) registry. Methods PURPLE collects longitudinal data on consecutive patients with pancreatic cancer seen since January 2016. Data were collated for patients with mPDAC from six Victorian sites, and analysed descriptively. Results Three hundred and sixty‐three patients with mPDAC were identified. Median age was 70 years (range 20–94 years). First‐line chemotherapy was administered in 195 (54%) patients. Prevalent regimens included gemcitabine‐nab‐paclitaxel (71 …

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE).Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease …

Background The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. Methods We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was …

Background RAS mutation testing now routinely informs the optimal management of metastatic colorectal cancer (mCRC), specifically the finding of a RAS mutation defines patients who will not benefit from treatment with an epidermal growth factor receptor inhibitor. Over time more RAS genes have been tested and more sensitive techniques used. Aims To review routine care RAS testing and results over time. Methods A retrospective analysis of the molecular data collected prospectively in the multi‐site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry from 2009 to 2018 was undertaken. Patients with RAS data were further analyzed. In parallel, the RAS mutation status of patients enrolled in the Test Tailor Treat (TTT) program was examined for 2011–2018. Results Of 2908 patients in the TRACC registry, 1892 (65%) were tested, with 898 (47%) of tested patients found to be RAS …