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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 (1) . 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 was 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 (20-94). First line chemotherapy was administered in 195 patients (54%). Prevalent regimens included gemcitabine-nab-paclitaxel (71%), gemcitabine alone (10%) and FOLFIRINOX (6%). Sixty-two of 195 (32%) patients who received first line treatment have proceeded to second line chemotherapy. Chemotherapy treated patients were younger (69 versus 73 years, p

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

Background Prior studies have reported for several cancer types that treatment in the private sector is associated with improved survival outcomes. Data for patients with locally advanced unresectable and metastatic pancreatic ductal adenocarcinoma (PDAC) have not previously been reported. Methods Analysis of patients from January 2016 to June 2020 registered to a multicentre prospective cancer database. Baseline demographic and clinicopathologic characteristics were compared. The Kaplan-Meier method was used to compare overall survival (OS). Multivariate Cox and logistic regression analyses were used to determine predictors of mortality and first-line chemotherapy treatment, respectively. Results Of 822 patients, 22.5% received private care. Private patients were older (median 71.5 vs. 68.9 years, p ≤ .05), had better performance status (ECOG 0 to 1: 82.2 vs. 73.5%, p = .05) and more likely to reside in an area with high socioeconomic advantage (67.0 vs. 19.6%, p ≤ .01). Private patients were more likely to receive first-line chemotherapy (69.7 vs. 54.2%, p ≤ .01) with logistic regression demonstrating private care (OR: 1.87, 95% CI: 1.20 to 2.97) as an independent predictor of receiving chemotherapy. Private patients had prolonged survival (median OS: 9.2 vs. 6.9 months, HR 1.2, p = .05). Receiving first-line chemotherapy was an independent predictor of mortality, but private care was not. Conclusions Care in the private system is associated with improved OS, with higher uptake of first-line chemotherapy appearing to be the main contributor. Given the discrepancy, further studies are needed to determine what factors are driving this difference.

B-Raf proto-oncogene (BRAF)-V600E mutations (BRAFmt) in colorectal cancer (CRC) predominantly occur in right-side (RS) primaries. In metastatic CRC (mCRC), there is substantial overlap between the reported features of BRAFmt and of an RS primary. To explore the significance of BRAFmt in a left-side (LS) primary, we analysed data from a multi-site mCRC registry. Tumours distal to the splenic flexure were considered LS. Of 3380 patients enrolled from June 2009 to June 2020, 214 (13%) of 1657 with known status were BRAFmt: 127 (24%) of 524 RS and 87 (8%) of 1133 LS. LS versus RS BRAFmt were younger (mean 59.5 vs. 65.1 years; p = 0.01), whereas sex (48 vs. 59% female; p = 0.13), mismatch repair-deficiency (dMMR) (16 vs. 21%; p = 0.47), and overall survival (OS) (median 15.1 vs. 17.7 months; p = 0.98) were similar. LS BRAFmt versus LS BRAF wildtype (wt) were of similar age (59.5 vs. 61.3 years; p = 0.28) with more females (48 vs. 37%; p = 0.04), more dMMR (16 vs. 1%; p < 0.0001), and inferior OS (median 15.1 vs. 36.6 months; p < 0.0001). Initial treatment with chemotherapy plus an epidermal growth factor receptor inhibitor produced median progression-free survival (PFS) of 4.3 versus 12.3 months (p = 0.20) for LS BRAFmt (n = 9) versus LS BRAFwt (n = 104). Initial chemotherapy and bevacizumab produced a median PFS of 7.6 versus 11.6 months (p = 0.02) for LS BRAFmt (n = 36) versus LS BRAFwt (n = 438), respectively. LS BRAFmt cancers share many features with RS BRAFmt cancers, including poor survival outcomes. Mature data on the activity of BRAF-targeted therapies in the first-line setting are eagerly awaited.

BACKGROUND: Evidence supporting dose modifications to reduce serious treatment-related adverse events of antineoplastic therapy is limited and frequently based on clinical trial protocols, which are not always generalisable to community patients. eviQ is an online resource with treatment protocols and recommendations for dose modification formulated by expert opinion and evidence-based review. Original recommended haematological thresholds to delay treatment were: neutrophil count

Trifluridine/tipiracil is available on the Australian Pharmaceutical Benefits Scheme for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor agents and anti-epidermal growth factor receptor agents. This article reviews trifluridine/tipiracil clinical data and presents practical information on its use in the management of refractory mCRC in Australia. Whereas the primary mechanism of action of fluoropyrimidines such as fluorouracil (5-FU) and capecitabine is enzyme inhibition of nucleotide synthesis, trifluridine/tipiracil primarily acts by incorporation into DNA, resulting in DNA dysfunction. Trifluridine/tipiracil has activity in patients with 5-FU-resistant tumors and can be considered in patients with prior intolerance or toxicity to 5-FU. In the pivotal phase III RECOURSE trial evaluating trifluridine/tipiracil in chemotherapy-refractory mCRC, efficacy benefits were observed across all a priori prognostic subgroups including those defined by age (≥65 and ≥75 years), geographical origin, primary tumor site or KRAS status. Trifluridine/tipiracil therapy benefits appropriately selected patients who have an ECOG performance status of 0 or 1, with no more than mild hepatic impairment or mild-to-moderate renal impairment, and who are capable of adhering to oral therapy safely. Appropriate dosing, monitoring for adverse events and effective management of side effects are essential.

Introduction Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localised and advanced pancreatic cancer and offers an expert opinion on current best practice. Areas covered For patients with localised disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable and locally advanced disease. Advances in metastatic disease are discussed including cytotoxic chemotherapy, targeted therapies and the role of genomic testing to identify patients with molecular alterations. Reviewed literature included; journal publications, abstracts presented at major international oncology meetings and ongoing clinical trials databases. Expert opinion Pancreatic cancer is a devastating diagnosis and despite recent advances has a very poor prognosis. Only a minority of patients, 20%, are diagnosed with potentially curable disease. The shifting paradigm towards neoadjuvant therapy may improve resectability and survival rates however robust evidence is required. Thus far, there has only been limited progress in advanced stage disease. Genomic testing may potentially identify more treatment targets although limited to small subgroups.

BackgroundDetection of circulating tumour DNA (ctDNA) after curative intent treatment reflects the presence of minimal residual disease and predicts for recurrence. DYNAMIC trial is a randomised phase II investigating the clinical utility of ctDNA-guided adjuvant treatment strategy compared with the standard of care (non-ctDNA based) approach in patients with stage II colon cancer. The primary trial endpoint is recurrence-free survival estimated from Kaplan Meier Method at 2 years. Secondary endpoints include proportion of patients treated with adjuvant chemotherapy, time-to-recurrence, overall survival, ctDNA clearance rate (investigational arm) and quality-adjusted life-years.ObjectiveTo outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis.MethodsThe SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data.Trial RegistrationANZ Clinical Trials Registry, ACTRN12615000381583. Registered on 27th April 2015.

This study uses incentive-compatible techniques to obtain valuations of 14 common poverty reduction interventions from (probable) aid recipients. Recipients’ valuations for these interventions are highly heterogeneous both across interventions and across recipients of the same intervention. Valuation for interventions does not correlate with overall poverty or with perceived need for specific interventions, suggesting that targeting individuals with high valuations based on recipient characteristics is difficult. Through simulations, this study assesses how various allocation mechanisms—cash transfers and voting—compare in generating recipient surplus in the allocation of aid. When markets function and constraints on joint private contributions to public goods do not bind, cash transfers generate considerably more recipient surplus than voting. Even when cash transfers cannot enable public goods and some services, they may still outperform voting at very low resource levels. However, as resource levels increase, voting dominates cash transfers from a surplus-maximization perspective.

Background The safety and efficacy of targeted therapy in older patients (≥ 70 years) with metastatic colorectal cancer is not well evaluated. Patients and Methods Outcomes of older patients (including overall survival [OS], progression-free survival [PFS], toxicity, and quality of life [QoL]) were compared to young patients using data from 2 large previously reported clinical trials, CO.17 (cetuximab vs. best supportive care) and CO.20 (cetuximab plus placebo vs. cetuximab plus brivanib). Only patients with wild-type KRAS tumors were included. Results A total of 251 (26.3%) of 955 patients were ≥ 70 years old. No significant differences in OS, PFS, or grade 3/4 adverse events were observed between older and younger patients treated with cetuximab (or cetuximab with placebo) in either trial. Younger patients trended toward superior OS in both CO.17 (hazard ratio = 1.80; P = .16) and CO.20 (hazard ratio = 1.34; P = .07). QoL maintenance favored younger patients in CO.17 (3.6 vs. 5.7 months; P = .046) but no difference of QoL maintenance was observed in the larger CO.20 trial (1.7 vs. 1.8 months; P = .64). Combination therapy of cetuximab and brivanib was significantly more toxic in older adults (87% vs. 77%; P = .03). Conclusion OS, PFS, and toxicities were similar between older and younger patients with wild-type KRAS metastatic colorectal cancer when treated with cetuximab. Both age groups likely experience similar QoL maintenance with cetuximab. Dual targeted therapy was significantly more toxic in older patients.

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute. METHODS: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers. Patient, tumor, treatment, and survival data were analyzed stratified by side. RESULTS: Of 2306 patients enrolled from July 2009-March 2018, 747 (32%) had an RC. Patients with RC were older, more likely to be female and have a Charlson score ≥3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases, and less likely to receive chemotherapy. Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs. 10.8 months, hazard ratio [HR] for progression in RC 1.38, P

ObjectiveMeaning and Purpose (MaP) therapy aims to enhance meaning-based coping through a life review that focuses on the value and worth of the person, key relationships, sources of fulfillment, roles, and future priorities in living life out fully. We sought to test the feasibility and acceptability of a six-session model of MaP therapy against a wait-list control cohort in a pilot study seeking effect sizes on measures of adaptation.MethodWe randomized patients with advanced cancer to MaP therapy or wait-list control, with measures administered at baseline and after 6–8 weeks. Wait-list patients could then crossover to receive therapy, with further measures collected postintervention. Adherence to the manualized model was sustained through weekly supervision and fidelity coding of recorded sessions. We used generalized estimating equations to control for baseline and any correlation of data.ResultFrom 134 eligible participants, 57 (43%) consented, and 40 of 45 (89%) offered therapy completed 6 sessions. Key barriers to consenting patients were poor health (15 refusers and 4 withdrawals) and death intervened in 6 participants. MaP therapy generated adequate effect sizes in posttraumatic growth (new possibilities, appreciation of life, and personal strength) and life attitudes (choices and goal seeking) to permit calculation of power for a formal randomized, controlled trial.Significance of resultsDelivery of this model of existentially oriented therapy is feasible and acceptable to patients. A properly powered randomized controlled trial is justified to examine the efficacy of this intervention.

Background Pancreatic cancer is noted for its late presentation at diagnosis, limited prognosis and physical and psychosocial symptom burden. This study examined associations between timing of palliative care referral (PCR) and aggressive cancer care received by pancreatic cancer patients in the last 30 days of life through a single health service. Method A retrospective cohort analysis of end-of-life (EOL) care outcomes of patients with pancreatic cancer who died between 2012 and 2016. Key indicators of aggressive cancer care in the last 30 days of life used were: ≥1 emergency department (ED) presentations, acute inpatient/intensive care unit (ICU) admission, and chemotherapy use. We examined time from PCR to death and place of death. Early and late PCR were defined as > 90 and ≤ 90 days before death respectively. Results Out of the 278 eligible deaths, 187 (67.3%) were categorized as receiving a late PCR and 91 (32.7%) an early PCR. The median time between referral and death was 48 days. Compared to those receiving early PCR, those with late PCR had: 18.1% (95% CI 6.8–29.4%) more ED presentations; 12.5% (95% CI 1.7–24.8%) more acute hospital admissions; with no differences in ICU admissions. Pain and complications of cancer accounted for the majority of overall ED presentations. Of the 166 patients who received chemotherapy within 30 days of death, 23 (24.5%) had a late PCR and 12 (16.7%) an early PCR, with no association of PCR status either unadjusted or adjusted for age or gender. The majority of patients (55.8%) died at the inpatient palliative care unit. Conclusion Our findings reaffirm the benefits of early PCR for pancreatic cancer patients to avoid inappropriate care toward the EOL. We suggest that in modern cancer care, there can sometimes be a need to reconsider the use of the term ‘aggressive cancer care’ at the EOL when the care is appropriately based on an individual patient’s presenting physical and psychosocial needs. Pancreatic cancer patients warrant early PCR but the debate must thus continue as to how we best achieve and benchmark outcomes that are compatible with patient and family needs and healthcare priorities.

This paper uses a large-scale field experiment in India to study attitudinal, behavioral, and cognitive constraints that can stymie the link between financial education and financial outcomes. The study complements financial education with (i) financial incentives on a financial literacy test to affect participant motivation, (ii) financial goal setting to provide a psychological nudge, and (iii) personalized financial counseling to enhance the intensity of treatment. The analysis finds no impact of financial incentives on learning but significant effects of both goal setting and counseling on real financial outcomes. These results identify important complements to financial education that can bridge the gap between financial knowledge and behavior change. Data and the online appendix are available at https://doi.org/10.1287/mnsc.2017.2819 . This paper was accepted by Amit Seru, finance.

Background Pancreatic cancer (PC) remains a highly fatal disease. There is a gap in the literature on the of quality care on survival in a real-world population. Objectives This study: (1) assessed compliance with a consensus set of quality indicators (QIs); and (2) evaluated the association between compliance with these QIs and survival. Methods Data were collected on a core set of quality indicators by the Upper Gastrointestinal Cancer Registry (UGICR) for patients diagnosed with PC between 1 January 2016 and 31 December 2019. Univariable and multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association between survival and patient characteristics, hospital characteristics and QIs, stratified by resectability. A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. Results 1061 patients were eligible for this study with 52% male, 71% over the age of 65, 23% potentially resectable and 51% with metastatic disease at diagnosis. 52% received some form of cancer directed treatment. Significant association with improved survival were: (1) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (2) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58) and (3) in the metastatic disease group included having documented ECOG at presentation and/or American society of Anaesthesiologists (ASA) performance status at a diagnostic procedure (HR, 0.65; 95 CI, 0.47-0.89), being seen by a medical oncologist and/or a radiation oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and having disease management discussed at an MDT meeting (HR, 0.79; 95 CI, 0.64-0.96). Conclusion Capture of a concise data set has enabled quality of care to be assessed and an analysis of factors associated with improved survival identified.

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 and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.

Introduction: The optimal management of isolated distant lymph node metastases (IDLNM) from a colorectal primary, is not clearly established. We aimed to analyze the outcomes of patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. Materials & Methods: Clinical data were collected and reviewed from the Treatment of Recurrent and Advanced Colorectal Cancer registry, a prospective, comprehensive registry for metastatic colorectal cancer (mCRC) treated at multiple tertiary hospitals across Australia. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with disease at other sites. Results: Of 3408 mCRC patients diagnosed 2009 to 2020, with median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC at other sites, patients with IDLNM were younger (mean age: 62.1 vs. 65.6 years, P = .02), more likely to have metachronous disease (57.0% vs. 38.9%, P < .01), be KRAS wild-type (74.6% vs. 53.9%, P< .01) and BRAF mutant (12.9% vs. 6.2%, P = .01). Amongst mCRC patients with IDLNM, 24 (25.8%) received treatment with curative intent and had a significantly better overall median survival than those treated with palliative intent (73.5 months vs. 23.2 months, P = .01). These 24 patients had an overall median survival similar (62.7 months, P = .82) to patients with isolated liver or lung metastases also treated with curative intent. Conclusion: Curative treatment strategies (radiotherapy or surgery), with or without systemic therapy, should be considered for mCRC patients with IDLNM where appropriate as assessed by the multidisciplinary team.

Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames posttrial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first-line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2-amplified breast cancer (BC) and castrate-resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice-changing trial. Registry patients were older than the matched trial cohort by a median of 2-6 years (all P =

We study the economic and psychological effects of a USD 1076 PPP unconditional cash transfer, a five-week psychotherapy program, and the combination of both interventions among 5,756 individuals in rural Kenya. One year after the interventions, cash transfer recipients had higher consumption, asset holdings, and revenue, as well as higher levels of psychological well-being than control households. In contrast, the psychotherapy program had no measurable effects on either psychological or economic outcomes, both for individuals with poor mental health at baseline and others. The effects of the combined treatment are similar to those of the cash transfer alone. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

The management of metastatic colorectal cancer patients with a poor performance status (PS) continues to be a clinical dilemma, with the potential activity and safety of treating this population remaining poorly understood. Few of these patients are enrolled onto clinical trials, and poor PS is often multifactorial.We analyzed the Treatment of Recurrent and Advanced Colorectal Cancer registry to describe treatment practices and outcomes in poor (Eastern Cooperative Oncology Group [ECOG] PS 2) and very poor PS (ECOG PS2) patients to explore the relationship between age, tumor burden, comorbidities, and PS, and to evaluate the benefit of systemic therapy. Standard descriptive statistical methods, Kaplan-Meier analysis, and a multivariate Cox regression model were used.Of 2769 registry patients (diagnosed January 2009 to June 2018), 329 (12%) and 182 (7%) patients had a poor and very poor PS, respectively. Good PS patients were more likely to receive systemic therapy than poor and very poor PS patients (85%, 55%, and 21.5%, P .0001), but clinician assessed response was observed in all subsets (53%, 41%, and 29%, P = .0003). Treatment with chemotherapy was associated with longer median overall survival across PS groups. Exploratory analysis based on comorbidity score and tumor burden subgroups demonstrated a consistently positive overall survival association with treatment. Benefit was observed where poor overall survival was attributable to medical comorbidities and to tumor burden.In routine clinical care, a substantial proportion of poor and very poor PS patients receive active treatment, which is often associated with meaningful clinical benefit.

3531 Background: Surgical resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether such benefit is consistently observed for BRAF V600E mutant (MT) and wild type (WT) mCRC. We conducted a retrospective analysis to explore the influence of BRAF mutation status on survival outcomes after metastasectomy. Methods: Data collected from two large prospective population databases in Australia (Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) and South Australian cancer registry). Overall survival (OS) and recurrence free survival (RFS) for BRAF MT and WT mCRC were evaluated by Kaplan-Meier method and compared by log-rank test. Results: 513 patients who had undergone metastasectomy were identified, 6% were BRAF MT. Median age 63. Metastasectomy rate was lower in BRAF MT (13 v 27%). In BRAF WT, 4% underwent resection of metastases (mets) in >1 organ at diagnosis and 5% had 3 or 4 metastasectomies versus none in BRAF MT. Median OS in BRAF MT v WT: 25.7 v 48.5 months (HR 1.95; 1.18-3.22). In a multivariate model adjusting for variables which were significant on univariate analysis, OS differences were not statistically significant. Right primary tumor, intact primary, >1 metastatic sites at diagnosis, non R0 resection, peritoneal mets and synchronous mets were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 v 19 months, p=0.09). Rate of downsizing was higher with triplet chemo than doublet +/- bevacizumab or doublet/EGFR in BRAF WT (50 v 30%) as well as MT (33 v 11%). Conclusions: Median OS was > 2 years in BRAF MT V600E after metastasectomy in this study consistent with an OS benefit. OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Presence of BRAF MT should not impact patient selection for metastasectomy.[Table: see text]

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 most common choice (51%), followed by FP-irinotecan (15%), trifluridine/tipiracil (11%), mono-chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP-doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP-doublet (18%), mono-chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4-41.2), and median time on third-line treatment was 3 months (range 0.1-40). Conclusions In real-world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.

PURPOSE Metastatic colorectal cancers (mCRCs) assigned to the transit-amplifying (TA) CRCAssigner subtype are more sensitive to anti–epidermal growth factor receptor (EGFR) therapy. We evaluated the association between the intratumoral presence of TA signature (TA-high/TA-low, dubbed as TA-ness classification) and outcomes in CRCs treated with anti-EGFR therapy. PATIENTS AND METHODS The TA-ness classes were defined in a discovery cohort (n = 84) and independently validated in a clinical trial (CO.20; cetuximab monotherapy arm; n = 121) and other samples using an established NanoString-based gene expression assay. Progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) according to TA-ness classification were assessed by univariate and multivariate analyses. RESULTS The TA-ness was measured in 772 samples from 712 patients. Patients (treated with anti-EGFR therapy) with TA-high tumors had significantly longer PFS (discovery hazard ratio [HR], 0.40; 95% CI, 0.25 to 0.64; P < .001; validation HR, 0.65; 95% CI, 0.45 to 0.93; P = .018), longer OS (discovery HR, 0.48; 95% CI, 0.29 to 0.78; P = .003; validation HR, 0.67; 95% CI, 0.46 to 0.98; P = .04), and higher DCR (discovery odds ratio [OR]; 14.8; 95% CI, 4.30 to 59.54; P < .001; validation OR, 4.35; 95% CI, 2.00 to 9.09; P < .001). TA-ness classification and its association with anti-EGFR therapy outcomes were further confirmed using publicly available data (n = 80) from metastatic samples (PFS P < .001) and patient-derived xenografts ( P = .042). In an exploratory analysis of 55 patients with RAS/BRAF wild-type and left-sided tumors, TA-high class was significantly associated with longer PFS and trend toward higher response rate (PFS HR, 0.53; 95% CI, 0.28 to 1.00; P = .049; OR, 5.88; 95% CI, 0.71 to 4.55; P = .09; response rate 33% in TA-high and 7.7% in TA-low). CONCLUSION TA-ness classification is associated with prognosis in patients with mCRC treated with anti-EGFR therapy and may further help understanding the value of sidedness in patients with RAS/BRAF wild-type tumors.

PURPOSE BRCA1 or BRCA2 ( BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.

Background The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. Patients and Methods Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m2, then 250 mg/m2 cetuximab weekly, with or without irinotecan 180 mg/m2 every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life. Results From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P = .008); response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial); P = .04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%); global and specific quality of life scores did not differ. Conclusion In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.

Background Two germ line Fc‐γ receptor (FCGR) polymorphisms, rs1801274 [FCGR2A; His(H)131Arg(R)] and rs396991 [FCGR3A; Phe(F)158Val(V)], produce altered proteins through amino acid substitutions. We previously reported that the FCGR2A H/H genotype was associated with longer overall survival (OS) in cetuximab‐treated chemotherapy‐refractory patients with metastatic colorectal cancer. Here, we aimed to replicate and extend this finding in the Canadian Clinical Trials Group CO.20 trial. Methods After germ line DNA genotyping, polymorphic relationships with survival were assessed using log‐rank tests and hazard ratios (HR) from Cox proportional hazard models, adjusting for known prognostic factors. The dominant genetic inheritance model was used for the main analysis. Results Of 592 wild‐type KRAS patients treated with cetuximab, those with the FCGR2A H/H genotype (n = 165, 28%) had improved OS (HR: 0.66, P

Summary Background Napabucasin is a first-in-class cancer stemness inhibitor that targets STAT3, which is a poor prognostic factor in colorectal cancer. This study aimed to test napabucasin in advanced colorectal cancer. Methods This study was a double-blind randomised phase 3 trial done at 68 centres in Canada, Australia, New Zealand, and Japan. Patients with advanced colorectal cancer with a good Eastern Cooperative Oncology Group (ECOG) performance status (0–1) for whom all available standard therapies had failed were eligible for the study. Patients were randomly assigned (1:1) to receive placebo or napabucasin through a web-based system with a permuted block method, after stratification by ECOG performance status, KRAS status, previous VEGF inhibitor treatment, and time from diagnosis of metastatic disease. Napabucasin 480 mg or matching placebo was taken orally every 12 h. All patients received best supportive care. The primary endpoint was overall survival assessed in an intention-to-treat analysis. This is the final analysis of this trial, which is registered at ClinicalTrials.gov, number NCT01830621. Findings Accrual began on April 15, 2013, and was stopped for futility on May 23, 2014, at which point 282 patients had undergone randomisation (138 assigned to the napabucasin group and 144 to the placebo group). Overall survival did not differ significantly between groups: median overall survival was 4·4 months (95% CI 3·7–4·9) in the napabucasin group and 4·8 months (4·0–5·3) in the placebo group (adjusted hazard ratio [HR] 1·13, 95% CI 0·88–1·46, p=0·34). The safety population included 136 patients in the napabucasin group and 144 patients in the placebo group. More patients who received napabucasin had any grade of treatment-related diarrhoea (108 [79%] of 136 patients), nausea (69 [51%]), and anorexia (52 [38%]) than did patients who received placebo (28 [19%] of 144 patients, 35 [24%], and 23 [16%], respectively). The most common severe (grade 3 or worse) treatment-related adverse events were abdominal pain (five [4%] patients receiving napabucasin vs five [3%] receiving placebo), diarrhoea (21 [15%] vs one [1%]), fatigue (14 [10%] vs eight [6%]), and dehydration (six [4%] vs one [1%]). 251 (89%) patients had data on pSTAT3 expression, of whom 55 (22%) had pSTAT3-positive tumours (29 in the napabucasin group, 26 in the placebo group). In a prespecified biomarker analysis of pSTAT3-positive patients, overall survival was longer in the napabucasin group than in the placebo group (median 5·1 months [95% CI 4·0–7·5] vs 3·0 months [1·7–4·1]; HR 0·41, 0·23–0·73, p=0·0025). Interpretation Although there was no difference in overall survival between groups in the overall unselected population, STAT3 might be an important target for the treatment of colorectal cancer with elevated pSTAT3 expression. Nevertheless, these results require validation. Funding Canadian Cancer Society Research Institute and Boston Biomedical.

248 Background: Quality indicators (QI) are essential to monitor the efficacy of cancer care and to guide quality improvement, however many are derived from ‘expert consensus’ and are not validated against outcomes. Moreover, the majority of oncological QI are defined in the surgical setting, with only a paucity of QI for the treatment of metastatic disease. We aimed to define and validate novel QI for metastatic colorectal cancer (mCRC) based on therapeutic approaches associated with a proven survival benefit. Methods: Data was analysed from TRACC, a multisite Australian registry collecting prospective demographic, tumour, treatment and outcome data for mCRC. We identified all patients diagnosed across 11 hospitals and explored variation by site with regards to patient and tumour characteristics, first-line chemotherapy administration and resection of oligometastatic disease. Log-rank testing and Kaplan-Meier curves compare overall survival (OS) between sites, and Pearson correlation was used to assess associations with each QI. Results: We examined data from 3132 patients diagnosed with mCRC between July 2009 – April 2021. Median age was 66 years (range 62 – 71 years by site), ECOG 0-1 81% (range 69 – 96% by site), and Charlson Comorbidity Index ≤2 43% (33 – 59% by site). Multivariate analysis confirmed association of known adverse prognostic factors with inferior OS (poor ECOG, right sided primary, KRAS or BRAF mutation, all p 2 = 0.851), rate of liver resection (9.8 – 23.2% by site) was moderately correlated (R2 = 0.523), and rates of active treatment with first-line chemotherapy (63 - 90% by site) were weakly correlated (R2 = 0.209). Other proposed QI such as rates of lung metastases resection or chemotherapy administration in the elderly showed significant variation by site, but did not correlate with survival. Conclusions: There is significant variation in OS for patients with mCRC in these Australian hospitals, with major differences in treatment approaches. Treatment strategies known to improve survival outcomes, such as triplet FOLFOXIRI chemotherapy and resection of liver metastases, may be potential QI to benchmark and track quality improvement over time. Further analysis will determine the impact of baseline patient populations between sites, and to correlate these QI with other quality measures.

Introduction: eviQ Cancer Treatments Online is a free, web-based resource providing access to over 600 evidence-based treatment protocols in medical oncology, radiation oncology, hematology and cancer genetics. With over 60 000 registrants from 148 countries, eviQ is widely used by cancer clinicians globally. The aim of this study was to examine the perceived quality of eviQ by Australian medical oncologists, the impact it had on their knowledge and practice, and the effect it had on their patients. Methods: A web-based survey was administered to members of the Medical Oncology Group of Australia by email. Two reminders emails were sent to encourage participation. Results: Of the 97 respondents (15%), all but one, were practicing in Australia, with varying years of oncology experience ( 10 years: 39%). eviQ was most frequently used as a source for providing patient information sheets on chemotherapy side effects, with 57% of respondents using eviQ for this purpose. Other uses included accessing side effect information (27%), checking drug doses (26%) and guiding dose adjustments (22%). The majority of respondents rated eviQ as current, accurate and relevant with over 90% agreeing that eviQ was of a high quality. Most of the respondents reported that they provided better care with enhanced patient experiences as a result of using eviQ. Conclusions: eviQ was highly regarded by Australian medical oncologists who responded to our survey. The results suggested that usage of eviQ had a positive impact on individual knowledge, practice and promoted better patient-centered care.

The share of people living in extreme poverty fell from 36 percent in 1990 to 10 percent in 2015 but has continued to increase in many fragile and conflict-affected areas where half of the extreme poor are expected to reside by 2030. These areas are also where the least evidence exists on how to tackle poverty. This paper investigates whether the Targeting the Ultra Poor program can lift households out of poverty in a fragile context: Afghanistan. In 80 villages in Balkh province, 1,219 of the poorest households were randomly assigned to a treatment or control group. Women in treatment households received a one-off “big-push” package, including a transfer of livestock assets, cash consumption stipend, skills training, and coaching. One year after the program ended—two years after assets were transferred—significant and large impacts are found across all the primary pre-specified outcomes: consumption, assets, psychological well-being, total time spent working, financial inclusion, and women’s empowerment. Per capita consumption increases by 30 percent (USD 24 purchasing power parity, USD 7 nominal per month) with respect to the control group, and the share of households below the national poverty line decreases from 82 percent in the control group to 62 percent in the treatment group. Using modest assumptions about consumption impacts, the intervention has an estimated internal rate of return of 26 percent, excluding non-monetized improvements in psychological well-being, women’s empowerment, and children’s health and education. These findings suggest that “big-push” interventions can dramatically reduce poverty in fragile and conflict-affected regions.

e18723 Background: Chemotherapy at the end of life (CEOL) is widely accepted as an indicator of aggressive care. However, the evidence is limited primarily to single-centre experiences, with no consensus regarding acceptable benchmarks for CEOL, nor how this may be changing over time and with novel treatment options. We describe ‘real world’ CEOL in two large, multisite Australian registries of metastatic colorectal cancer (mCRC) and both locally advanced and metastatic pancreatic cancer (PC). Methods: Data was analysed from the TRACC and PURPLE registries, two large prospective multisite Australian cancer registries collecting prospective demographic, tumour, treatment and outcome data for mCRC and PC respectively. We identified all decedents between May 2009 and November 2020, determined the proportion who died within 14 or 30 days of chemotherapy (14D / 30D), or within 30D after a new line of therapy, defined as the first cycle of a new treatment regimen. Using univariate analysis, we compared baseline demographic and clinicopathological variables and trends over time. Results: 1505 mCRC and 602 PC decedents were identified. 20.9% of decedents (21.6% mCRC and 19.3% PC) received chemotherapy within 30D, and 11.5% within 14D (12.3% mCRC and 9.6% PC). There were lower rates of 30D CEOL after the first cycle of a new line of therapy (4.3% mCRC and 5.7% PC). Rates of CEOL decreased over the study period for mCRC (median rate of initial 3-year period 28% versus 15% in last 3-year period), but remained largely static for PC (18.9% versus 17.9%). 30D CEOL was more likely with palliative than curative intent treatment (mCRC OR 1.6, 95% CI 1.14-2.25, p = 0.007, PC OR 5.3, 95% CI 1.6-17.8), and advanced rather than local disease in PC (PC OR 2.59, 95%CI 1.6-4.1, p < 0.001). There was a trend towards CEOL and poorer performance status (ECOG) across all groups, only significant for 30D CEOL mCRC (OR 1.51, 95% CI 1.04-2.2). There was no association between CEOL and patient age, gender, Charlson comorbidity score or lines of therapy. Conclusions: Real-world rates of CEOL are higher in our cohorts of mCRC and PC patients than historical benchmarks but comparable to contemporary reports, which may be due to a wider array of available active treatments. Overall rates are decreasing over time for mCRC but static for PC, which may reflect the poorer overall survival for PC and lack of new effective therapies. The lower rates of death after new lines of therapy may signify that CEOL is more likely with existing treatment regimens and that clinicians are less likely to initiate a new chemotherapeutic regimen at EOL.

80 Background: The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib was granted accelerated approval by the US Food and Drug Administration for patients with BRCA+ mCRPC based on results from the phase 2 TRITON2 study (NCT02952534). The TP53 tumor suppressor gene is among the most frequently mutated genes in human cancers, including mCRPC, and alterations in TP53, PTEN, and RB1 are associated with poor prognosis in patients with prostate cancer and other tumor types. We present data on co-occurring alterations in patients with BRCA+ mCRPC treated with rucaparib in TRITON2. Methods: Patients had progressed on 1–2 lines of androgen receptor-directed therapy and 1 taxane-based chemotherapy and were treated with rucaparib 600 mg BID. Tissue and/or cell-free DNA extracted from plasma samples were profiled comprehensively for genomic alterations using Foundation Medicine, Inc., next-generation sequencing assays. Objective response rate (ORR) was assessed per modified Response Evaluation Criteria in Solid Tumors and Prostate Cancer Working Group 3 criteria by independent radiologic review of patients with measurable disease. Prostate-specific antigen (PSA) response rate (≥50% decrease from baseline) was assessed in all patients. Results: Tissue and/or plasma samples were available for 114/115 patients with BRCA+ mCRPC (visit cutoff date: Dec. 23, 2019). Among patients with BRCA+ mCRPC who had samples available for comprehensive genomic profiling, 36.8% (42/114) had a co-occurring alteration in TP53. Deleterious alterations in PTEN were observed in 34.2% (39/114) of patients, 44% (17/39) of which were homozygous deletions of PTEN. RB1 loss was observed in 12.3% (14/114) of patients and was seen more frequently in patients with measurable disease (18.0%, 11/61) than in patients with non-measurable disease (5.7%, 3/53). Although patients with and without TP53 mutations had generally similar baseline demographics and disease characteristics, visceral disease was more prevalent in patients with TP53 mutations (54.8%; 23/42) than in those without them (29.2%; 21/72). Similar ORR and PSA response rates were seen in patients with BRCA+ mCRPC with or without TP53 mutation, with a non-significant trend towards lower response rates in patients with co-occurring TP53 alterations. Conclusions: Results from TRITON2 showed antitumor activity for rucaparib in patients with BRCA+ mCRPC associated with or without co-occurring alterations in TP53. Demographics and additional efficacy analyses in genomic subgroups with co-occurring alterations in TP53, PTEN, and RB1 will be reported. Clinical trial information: NCT02952534. [Table: see text]

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: 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 all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 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 and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

84 Background: The optimal management of isolated distant lymph node metastases (IDLNM) in metastatic colorectal cancer (mCRC) is not clearly established. Small case series and prior data from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry support the use of radical treatment with curative intent (local resection, chemo-radiation or stereotactic radiotherapy), which may lead to better outcomes in mCRC patients with IDLNM. Aims: This study investigates the clinical characteristics and outcomes of mCRC patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. Methods: Clinical data were collected and reviewed from the TRACC registry, a prospective, comprehensive registry for mCRC from multiple tertiary hospitals across Australia from 01/07/2009 to 30/06/2020. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with other organ metastases. Fisher exact test was used for significance tests and Kaplan Meier curves for survival analyses. Results: Of 3408 mCRC patients with a median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC with other organ metastases, patients with IDLNM were younger (mean age: 62.1 vs 65.6 years, p=0.0200), more likely to have metachronous disease (57.0% vs 38.9%, p=0.0005), be KRAS wild-type (74.6% vs 53.9%, p=0.0012) and BRAF mutant (12.9% vs 6.2%, p=0.0100). There was no overall survival difference between with IDLNM and those with other organ metastases (median OS 27.24 vs 25.92 months, p=0.2300). Twenty-four patients (25.8%) with IDLNM received treatment with curative intent, with a trend towards improved overall survival compared to those with other organ metastases treated with curative intent (73.5 vs 62.7 months, p=0.8200). Amongst mCRC patients with IDLNM, those who received treatment with curative intent had a significantly better overall survival than those treated with palliative intent (73.5months vs 23.2 months, p=0.0070). Conclusions: Our findings suggest that there are differences in the patterns of presentation of IDLNM and other organ metastases. Radical treatment with curative intent options should be considered for mCRC patients with IDLNM where appropriate.

Background Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. Methods Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed. Results Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)).1 Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events – 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623.1 Conclusions The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.

Advanced esophagogastric cancers are aggressive malignancies with an extremely poor prognosis. Palliative chemotherapy remains disappointing, with median survival of

Introduction This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. Methods This is a retrospective analysis of the prospective ‘Treatment of Recurrent and Advanced Colorectal Cancer’ registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). Results One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. Conclusions This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice.

e16048 Background: Bevacizumab remains the dominant biologic treatment option for RAS mutant (RASmt) metastatic colorectal cancer (mCRC). While the health economic impact of bevacizumab in the RASmt subpopulation may deviate from its use in the general mCRC population, this has never been investigated. This study uses the power of real-world data to assess the cost-effectiveness of doublet chemotherapy with compared to without bevacizumab (ChemBev and ChemOnly, respectively) for first-line treatment of RASmt mCRC, while accounting for subsequent treatment in second and third line. Methods: Data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was analyzed to populate a discrete event simulation of three treatment lines, surgery of primary tumor and metastases, hospitalizations following serious adverse events, and best supportive care. Imbalance in baseline patient and disease characteristics was corrected for in all analyses using inverse probability weights. Costs were included from an Australian public payer perspective in Australian dollars (AUD). All health and economic outcomes were discounted at 5% per year. Results: Of the 507 included RASmt mCRC patients that started first-line treatment in the 2010 – 2017 time period, 345 received ChemBev and 162 ChemOnly. The corrected median time on first-line treatment was 7.1 months (95% confidence interval: 6.4 – 8.0) for ChemBev and 4.1 months (3.5 – 5.1) for ChemOnly. Time on second- and third-line treatment was comparable between the groups. Corrected overall survival was 22.6 months (21.7 – 24.0) for ChemBev and 14.3 months (12.1 – 21.7) for ChemOnly. In terms of the health economic impact, mean life years were 1.9 for ChemBev and 1.5 for ChemOnly, and mean costs were AUD 93,025 and AUD 44,929 per patient, respectively. The resulting incremental cost-effectiveness ratio (ICER) of ChemBev compared to ChemOnly was AUD 149,317 per life-year gained (LYG). Conclusions: In contrast to results from clinical trials, overall survival was substantially longer for patients who received bevacizumab, which can possibly be attributed to an imbalance between groups despite correction for known prognostic factors. At an ICER of AUD 149,317 per LYG, the economic burden of upfront treatment with bevacizumab was found to be substantial and consistent with estimates for the general mCRC population. This is mainly caused by the duration of first-line treatment, which was significantly longer for ChemBev.

e16072 Background: The KRASG12C mutation is present in 3% of colorectal cancer and is of particular interest given the recent development of specific targeting drugs. Previous data suggest KRAS (all) mutations may impact prognosis. Here we assess the clinical features and outcomes of real world patients with KRASG12C mutant metastatic colorectal cancer (mCRC) to explore any clinicopathologic associations and prognostic impact. Methods: Patients diagnosed with mCRC between January 2011 and December 2018 were included in this prospective mCRC registry. Patients with BRAF mutations, unknown or unspecified KRAS variants were excluded. Clinicopathologic features, treatment and overall survival (OS) were compared for RAS wildtype (RASWT) and KRASG12C mutant patients, and between KRASG12C and other (RASother) mutations. Results: Of 1308 patients analysed, 674 (52%) were RASmut, of whom 56 (8.3%) were KRASG12C. More patients with KRASG12C were female compared to RASother and RASWT (Table). No differences were observed in primary tumor location, number of metastatic sites and distribution of metastases. The proportion of patients undergoing metastasectomy was similar between KRASG12C and RASother, and KRASG12C and RASWT. There was no difference in the proportion of patients receiving systemic therapy. RASWT patients received more lines of therapy. Median OS was similar between KRASG12C, RASother, and RASWT: 31.7 vs 29.2 vs 31.8 months respectively (P = 0.545). Conclusions: KRASG12C mutations were observed in 4.3% of mCRC patients and in 8.3% of RAS mutant cases. Patients with KRASG12C have comparable clinical features to RASWT or RASother mCRC. Treatment and survival were also similar between groups. KRASG12C does not appear to be prognostic, but may be an important predictive biomarker as promising targeted therapies continue to be developed. [Table: see text]

178 Background: The phase 2 TRITON2 study (NCT02952534) is evaluating the PARP inhibitor rucaparib in pts with mCRPC and a deleterious germline or somatic alteration in BRCA ( BRCA pts) or 1 of 13 other DNA damage repair (DDR) genes. Methods: Eligible pts had progressed on 1–2 lines of androgen receptor-directed therapy and 1 taxane-based chemotherapy. Deleterious DDR gene alterations were identified from central testing of plasma and/or tissue samples by Foundation Medicine or from local testing. Results: As of Jul 2, 2019 (visit cutoff), 98 BRCA pts had received rucaparib; median (range) duration of follow-up was 13.0 (4.1–25.8) mo. Confirmed objective response rate (ORR) in BRCA pts (with investigator-assessed measurable disease) and PSA response rates (in pts with and without measurable disease) are shown in the Table. A biallelic alteration was observed in 81.4% (35/43) of BRCA pts for whom zygosity could be determined, and pts with homozygous BRCA loss (20.4%; 20/98) demonstrated high ORR (66.7% [95% CI, 38.4-88.2]; 10/15) and PSA response rates (75.0% [95% CI, 50.9-91.3]; 15/20). The safety profile in BRCA pts was consistent with the overall TRITON2 pt population. Conclusions: Results from TRITON2 showed antitumor activity with rucaparib in pts with mCRPC and a deleterious BRCA alteration. Responses were observed in patients with germline or somatic alterations in BRCA1 or BRCA2. The activity of rucaparib in these and additional genomic subgroups (e.g., based on zygosity, plasma genomic testing, or co-occurring alterations) will be reported. Clinical trial information: NCT02952534. [Table: see text]

159 Background: There is conflicting evidence regarding benefit of perioperative chemotherapy (p-chemo) for metastatic colorectal cancer (mCRC) patients (pts) undergoing resection of metastases (mets). Aims: To describe use of and outcomes from p-chemo in mCRC pts who underwent resection of isolated liver or lung mets. Methods: Pts were identified from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a multi-centre registry of mCRC pts. P-chemo was defined as chemotherapy within 12 weeks of surgery. Multivariate (MV) analysis using a Cox proportional hazards model was undertaken. Results: 371 pts were identified. Median age was 64 (27 – 90), 169 (45%) had de novo stage IV disease, 96% were ECOG 0-1. 284 (77%) had liver-only and 87 (23%) lung-only mets. 242 (65%) pts received p-chemo (58 pre-op alone, 134 post-op alone, 50 both). 62 (19%) pts also received a biologic agent (47/62 pre-op). Median age was 68 and 61 years in no p-chemo and p-chemo groups, respectively (p

Background Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour. Aim To explore evolving pattern of metastatic colorectal cancer care over time in Australia. Methods We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry. Results From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders. Conclusion Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies.

Background The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis. Materials and Methods We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use. Results Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26). Conclusion Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.

Background: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. Methods: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel–Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. Results: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis,median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p

Introduction: Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6months of adjuvant chemotherapy is preferable in Stage III colon cancer.Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer.Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Objectives The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting. Materials and Methods Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65–74 vs. 75–84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis. Results Of 1439 patients, 363, 352, and 106 were aged 65–74, 75–84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65–74-, 75–84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%). Conclusion Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age.