INTRODUCTION:Combination immunotherapy (Ipi/Nivo) was approved in Australia in 2019 for metastatic clear cell kidney cancer (mccRCC) patients with International Metastatic Database Consortium (IMDC) intermediate and poor-risk. Although selected patients can safely delay treatment due to indolent disease, delaying treatment beyond 1 year in patients without other IMDC risk factors classifies them as favorable risk and prevents access to Ipi/Nivo. This study investigated the impact of Ipi/Nivo approval on timing of treatment initiation and outcomes. METHODS:Multicenter retrospective cohort study analyzing real-world data from the Kidney canceR Australian registry and Biobank (KRAB) was used to identify patients > 18 years with mccRCC who received systemic therapy. Patient demographics, time to systemic therapy (TTST) from diagnosis of metastatic disease, and outcomes were compared for patients diagnosed with metastatic disease before and from January 2019. RESULTS:A total of 494 patients met study criteria. The 256 patients diagnosed from 2019 had a significant decrease in both mean TTST (3.9 months from 15.3 months) and proportion with TTST ≥ 1 year (8.2% from 27.7%). More patients met criteria for intermediate and poor-risk disease from 2019 (61% from 49%). Of the 242 patients with de novo metastatic disease, the proportion with TTST ≥ 1 year decreased from 2019 (5.2% from 16.7%). Despite this, there was no significant difference in overall survival before and from 2019. CONCLUSION:Prescribing restrictions for Ipi/Nivo in Australia were associated with a substantial change in prescribing practice for patients with mccRCC, without any change in survival outcomes.

Background: Trifluridine/tipiracil (TT) is an oral fluoropyrimidine (FP) currently utilised in later-line therapy for metastatic colorectal cancer, with a unique mechanism of action and clinical activity in patients with prior FP failure. Preclinical data demonstrates synergistic activity with panitumumab or irinotecan, providing rationale for its use in earlier lines of treatment. PIT was a non-randomised, phase IB/II study determining the safety and tolerability of TT combined with panitumumab and irinotecan for first- or second-line management of RAS wildtype metastatic colorectal cancer. Methods: The part IB dose escalation study enrolled 3 patients before the MTD was determined from other published work. TT was dosed orally, BID 25 mg/m2 on days 1–5, with 6 mg/kg panitumumab and 180 mg/m2 irinotecan administered intravenously on day 1 of 14-day cycles. The phase II expansion study aimed to enrol 50 patients, with the primary endpoint modified to toxicity. Results: This study closed early due to slow recruitment, with the enrolment of 14 patients. Thirteen received PIT as first-line therapy for metastatic disease. A total of 64% experienced grade 3 toxicity (predominantly rash, electrolyte disturbances, diarrhoea, and neutropenia). One patient experienced grade 4 neutropenia, and there was one treatment-related death (neutropenic sepsis). At a median follow-up of 36 months, 12 patients had evaluable disease (PR: 58%; SD: 42%), with a 6-month PFS of 91%, a median PFS of 18.2 months, a median OS of 41.3 months, and a 12-month OS of 57%. Conclusions: The toxicity profile was notable for high rates of grade 3 rash and diarrhoea. Whilst the small patient numbers limit interpretation, there is a significant signal of activity for this combination, supporting this concept for future trials (ANZCTR number: ACTRN12617001190392, 2017 Aug 15).

IntroductionIntegrating health and social care to address unmet social needs is an emerging priority for health systems worldwide. Screening and referral interventions for unmet social needs, also known as Health Navigator (HN) interventions, in healthcare settings have shown mixed but promising results, mostly due to a large variability in intervention design and outcomes assessed. Most HN interventions are implemented in primary care, despite evidence that disadvantaged populations face substantial barriers to accessing such care, and these interventions are limited in Australia. To address this gap, we designed a HN intervention to address the unmet social needs of a disadvantaged population living with cancer presenting at an outpatient cancer treatment facility in South Australia. To our knowledge, this paper presents a protocol for one of the first feasibility and acceptability studies of an HN intervention in an Australian healthcare setting.Methods and analysisWe will conduct a single-centre study to explore the feasibility and acceptability of screening and referral for unmet social needs for patients attending an outpatient cancer clinic at a major metropolitan hospital serving a disadvantaged population in South Australia. Eligible participants are 18 years of age or older receiving treatment at the Northern Adelaide Cancer Centre, with an expected prognosis of minimum 6 months. During recruitment, a researcher will ask eligible participants to complete unmet social needs screening and baseline assessments. Participants with unmet social needs who request assistance will be connected with an HN. The HN will work with participants to prioritise their needs and provide referrals to community and government services with follow-up of over 6 months from enrolment. Post-HN intervention, all participants will be asked to complete repeat unmet social needs screening and repeat assessments. The primary criteria for determining feasibility success are: (1) recruitment rates, where 80% of eligible participants agree to unmet needs screening; (2) intervention uptake, where 80% of participants who report unmet social needs consent to assistance from a HN; (3) intervention completion, where 80% of participants receive HN assistance complete follow-up; (4) reasons for not completing intervention; and (5) participant and clinician acceptability of the intervention. Secondary outcomes include changes to unmet social needs and coping with cancer ability, quality of life and patient-reported experience measures. Thematic analysis will be applied to focus groups with clinicians and participants to assess intervention acceptability. Secondary clinical outcomes will be reported as effect size estimates for future trials. Based on previous work in this area, we will aim to recruit 350 participants. Study findings will be used to optimise recruitment and intervention components and develop suitable outcome measures for larger, randomised studies.Ethics and disseminationThe protocol has ethical approval from the Central Adelaide Local Health Network Human Research Ethics Committee (approval ID: 16448). Findings will be disseminated in research publications and non-academic formats for a variety of audiences.Trial registration numberAustralian New Zealand Clinical Trial Registry (ACTRN12622000802707p).Protocol date and version: 07 June 2022, V1.

This case report describes a case of anti-programmed cell death protein 1 (PD-1) antibody-related central diabetes insipidus without features of infiltrative process on neuroimaging. It involved a 63-year old man who was initially admitted for immunotherapy-related pneumonitis and was subsequently diagnosed with new central diabetes insipidus on the background of advanced non-small cell lung cancer treated with pembrolizumab. This clinical phenomenon is exceedingly rare and has been reported with anti-cytotoxic T lymphocytes-4 (CTLA-4) agent [1]. Central diabetes insipidus associated with anti-PD-1 monotherapy has only been described in three case reports [2-4]. Neuroimaging plays an important role to identify other process including metastatic infiltration. Multi-disciplinary patient care remains the key in managing patients with immunotherapyrelated endocrinopathies.

OBJECTIVE This study aims to investigate disparities in demographics, disease characteristics, treatment and overall survival between South Australian (SA) Indigenous and non-Indigenous patients with metastatic colorectal cancer (mCRC). DESIGN This employs a retrospective population study using the SA mCRC registry. SETTING The SA mCRC registry identifies mCRC patients from hospital encounters, histopathology reports, medical oncology letters, clinician notification, attendances at multidisciplinary meetings and death audits by the SA Cancer Registry. PARTICIPANTS A total of 2865 adult mCRC patients including 14 Indigenous patients were identified through the SA mCRC registry between February 2006 and August 2013. Patients were linked to the SA Cancer Registry to obtain Indigenous status. MAIN OUTCOME MEASURES Demographic, disease and treatment characteristics were compared using Chi-squared test and t-test; while overall survival defined as time to any cause of death was analysed using Cox regression. RESULTS No difference was observed for clinical characteristics, except for a higher proportion of Indigenous patients receiving chemotherapy (85.7% versus 58.5%; P = 0.04). The rate of liver surgery was similar across the two groups (21.0% versus 15.1%; P = 0.40). The median overall survivals were equivalent (11.9 months versus 15.1 months; hazard ratio = 1.00; 95% confidence interval for hazard ratio, 0.54-1.86). CONCLUSIONS Clinical characteristics and survival outcomes were similar between Indigenous and non-Indigenous patients captured on the SA mCRC registry, and outcome of those who have an access to comprehensive cancer care appeared independent of Indigenous status and in line with large clinical trials. Underestimation of Indigenous cases due to their lower utilisation of cancer service could not be excluded and ultimately the accurate reporting of these patients is crucial.

Objective: To compare the management and outcome of rural and metropolitan patients with metastatic colorectal cancer (mCRC) in South Australia.Design, setting and patients: Retrospective cohort study of patients with mCRC submitted to the South Australian mCRC registry between 2 February 2006 and a cut-off date of 28 May 2012.Main outcome measures: Differences in oncological and surgical management and overall survival (calculated using the Kaplan-Meier method) between city and rural patients.Results: Of 2289 patients, 624 (27.3%) were rural. There was a higher proportion of mate patients in the rural cohort, but other patient characteristics did not significantly differ between the cohorts. Equivalent rates of chemotherapy administration between city and rural patients were observed across each line of treatment (first line: 56.0% v 58.3%, P = 0.32; second line: 23.3% v 22.5%, P = 0.78; and third line: 10.1% v 9.3%, P = 0.69). A higher proportion of city patients received combination chemotherapy in the first-line setting (67.4% v 59.9%; P = 0.01). When an oxaliplatin combination was prescribed, oral capecitabine was used more frequently in rural patients (22.9% v 8.4%; P < 0.001). No significant difference was seen in rates of hepatic resection or other non-chemotherapy treatments between cohorts. Median overall survival was equivalent between city and rural patients (14.6 v14.9 months, P = 0.18).Conclusion: Patterns of chemotherapy and surgical management of rural patients with mCRC in SA are equivalent to their metropolitan counterparts and lead to comparable overall survival. The centralised model of oncologicat care in SA may ensure rural patients gain access to optimal care.

PURPOSE:Newer drugs incorporated in prophylactic regimens for chemotherapy-induced nausea and vomiting (CINV) have resulted in significantly reduced rates of this feared complication of cytotoxic chemotherapy. However, both delayed chemotherapy-induced nausea and breakthrough CINV remain difficult areas of management and require novel treatment strategies. Recent randomized trial evidence has suggested that olanzapine, an atypical antipsychotic, may have a role in both the prevention and treatment of CINV. A systematic review was conducted to assess the efficacy of olanzapine in (a) preventing CINV in highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) and (b) the treatment of breakthrough CINV. The toxicity of olanzapine in this setting was also reviewed. METHODS:MEDLINE, Embase and Cochrane Database of Systematic Reviews databases were searched to identify all randomized clinical trials (RCTs) investigating olanzapine in patients receiving chemotherapy. RESULTS:A total of 488 patients from three trials of CINV prophylaxis and 323 patients from three trials of breakthrough CINV were included. Regimens including olanzapine were associated with significant improvements in CINV prevention with both HEC and MEC. Single agent olanzapine for breakthrough nausea was superior to standard alternative options. CONCLUSION:Data from RCTs support the use of an olanzapine containing combination regimen as an option for CINV prophylaxis and single agent olanzapine for the treatment of breakthrough CINV. In the included trials, the short duration of olanzapine appears safe and well tolerated.

BACKGROUND:Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results.METHODS:We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed.RESULTS:Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%).CONCLUSION:Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer.

596 Background: Previous reports have described differences in biology and outcome based on whether the primary is R or L sided. Possible differences in response to biological agents have also been reported based on side of primary lesion (SY Brule et al., JCO31, 2013 (supp #3528). Methods: We explored the SA mCRC registry to assess if there were any differences in patient characteristics, treatment received and outcomes based on whether the primary was R (caecum to transverse colon) or L (splenic flexure to rectum) sided (JA Bufill, Ann Int Med. 113, 1990, 779-788). KM was used for survival outcomes and Cox proportional hazards regression modeling was used to assess defined prognostic markers. Results: 2,877 patients were analysed. 33% had R sided primary. Major differences between R and L respectively are as follows; Female 51.3% vs. 37.9% (p = <0.0001), Med age 75.8 yrs vs. 70.5yrs (p = <0.0001), poorly differentiated pathology 34.3% vs. 20.8% (p = <0.0001), KRAS mutation 48% vs. 37% (p = 0.023), and liver surgery 10.5% vs. 16.3% (p = <0.0001). Analysis of chemotherapy (defined as either cytotoxic and/or molecular-targeted) revealed similar rates of first-line therapy, but differences in rates of therapy beyond first-line R vs. L respectively; second-line 46% vs. 60.4%, third-line 17% vs. 30%, fourth-line 7% vs. 13%. There was however no difference in single agent vs. combination first-line therapy. The median overall survival (mOS) for the entire group R vs. L was 9.6 vs. 20.3 months (p <0.0001). For the group who had active therapy defined as chemotherapy (+/- metastasis resection), mOS was R 18.2 months vs. L 29.4 months (p <0.0001). For those (n = 123) who underwent liver resection (+/- chemotherapy) mOS was 6.2 years for both R and L (p = 0.32). Patients who were treated with only chemotherapy, the mOS was 10.7 mths vs. 15.3 mths for R v L (p = 0.0005). Conclusions: Patients with R sided primary have more negative prognostic factors and indeed have inferior outcomes when compared with those with a L sided primary. This did not appear to be the case for patients who were suitable for hepatic surgery.