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Discusses how, in 1970, Buena Vista College in northwestern Iowa, began to recognize that its faculty and students need first-hand experience with Asian cultures, but never developed a specific plan for institutionalizing an international perspective until recently. Search for high-value, low-cost experiences with faculty; Exchanges provide college with Asian language teachers; Recruiting international students; Institutionalizing the international perspective; Change on campus.

Purpose: The aim of this randomized, placebo-controlled, two-stage, phase II/III trial was to determine the efficacy of an oral cannabis extract in adults with refractory nausea and/or vomiting during moderately or highly emetogenic, intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Here, we report results of the prespecified combined analysis including the initial phase II and subsequent phase III components., Patients and Methods: Study treatment consisted of oral capsules containing either tetrahydrocannabinol 2.5 mg plus cannabidiol 2.5 mg capsules (THC:CBD) or matching placebo, taken three times a day from days -1 to 5, in addition to guideline-consistent antiemetics. The primary measure of effect was the difference in the proportions of participants with no vomiting or retching and no use of rescue medications (a complete response) during hours 0-120 after the first cycle of chemotherapy on study (cycle A)., Results: We recruited 147 evaluable of a planned 250 participants from 2016 to 2022. Background antiemetic prophylaxis included a corticosteroid and 5-hydroxytryptamine antagonist in 97%, a neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD compared with placebo improved the complete response rate from 8% to 24% (absolute difference 16%, 95% CI, 4 to 28, P = .01), with similar effects for absence of significant nausea, use of rescue medications, daily vomits, and the nausea scale on the Functional Living Index-Emesis quality-of-life questionnaire. More frequent bothersome adverse events of special interest included sedation (18% v 7%), dizziness (10% v 0%), and transient anxiety (4% v 1%). There were no serious adverse events attributed to THC:CBD., Conclusion: THC:CBD is an effective adjunct for chemotherapy-induced nausea and vomiting despite standard antiemetic prophylaxis, but was associated with additional adverse events. Drug availability, cultural attitudes, legal status, and preferences may affect implementation. Future analyses will evaluate the cost-effectiveness of THC:CBD.

Background: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC., Methods: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15., Results: IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; p = 0.03 and Day 21; p = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; p < 0.0001 and Day 42; p < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (p = 0.03), but was not replicated by recombinant GDF15., Conclusions: Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

Objectives: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials., Study Design: Retrospective observational study; review of patient records in fifteen Australian institutions., Setting, Participants: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme., Main Outcome Measures: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival., Results: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths., Conclusion: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

In this paper, we describe the Project Extension for Community Healthcare Outcomes+ (ECHO+) model and evaluation plan for incorporating changes to primary care delivery, improving patient and clinician outcomes, and making long-term system improvements.

Background: The aim of this study was to investigate the antitumour activity, safety, and tolerability of pamiparib plus tislelizumab in patients with previously treated advanced solid tumours., Methods: In this study, patients were enrolled into eight arms by tumour type. All received pamiparib 40 mg orally twice daily plus tislelizumab 200 mg intravenously every 3 weeks. The primary endpoint was objective response rate (ORR), assessed by the investigator per Response Evaluation Criteria in Solid Tumours v1.1. Secondary endpoints included duration of response (DoR), safety, and tolerability., Results: Overall, 180 patients were enrolled. In the overall population, the ORR was 20.0% (range: 0-47.4 across study arms), with median DoR of 17.1 months (95% confidence interval [CI]: 6.2, not estimable [NE]). The highest ORR was observed in the triple-negative breast cancer (TNBC) arm (patients with BRCA1/2 mutations and/or homologous recombination deficiency) (ORR: 47.4%; median DoR: 17.1 months [95% CI: 3.0, NE]). Treatment-emergent adverse events (TEAEs) of ≥Grade 3 occurred in 61.7% of patients. Serious TEAEs occurred in 50.0% of patients., Conclusions: Pamiparib plus tislelizumab showed a variable level of antitumour activity in patients with advanced solid tumours, with the highest ORR in TNBC and was associated with a manageable safety profile., Clinical Trial Registration: ClinicalTrial.gov: NCT02660034., (© 2023. Crown.)

Purpose: To address the paucity of data in patients with historically poor outcomes, we conducted the single-arm phase IIIb CheckMate 401 study to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in clinically diverse patient populations with advanced melanoma., Methods: Treatment-naive patients with unresectable stage III-IV melanoma received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg (240 mg following a protocol amendment) once every 2 weeks for ≤24 months. The primary end point was the incidence of grade 3-5 select treatment-related adverse events (TRAEs). Overall survival (OS) was a secondary end point. Outcomes were evaluated in subgroups defined by Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastasis status, and melanoma subtype., Results: In total, 533 patients received at least one dose of study drug. Grade 3-5 select TRAEs affecting the GI (16%), hepatic (15%), endocrine (11%), skin (7%), renal (2%), and pulmonary (1%) systems occurred in the all-treated population; similar incidence rates were observed across all subgroups. At 21.6 months' median follow-up, 24-month OS rates were 63% in the all-treated population, 44% in the ECOG PS 2 subgroup (including patients with cutaneous melanoma only), 71% in the brain metastasis subgroup, 36% in the ocular/uveal melanoma subgroup, and 38% in the mucosal melanoma subgroup., Conclusion: Nivolumab plus ipilimumab followed by nivolumab monotherapy was tolerable in patients with advanced melanoma and poor prognostic characteristics. Efficacy was similar between the all-treated population and patients with brain metastases. Reduced efficacy was observed in patients with ECOG PS 2, ocular/uveal melanoma, and/or mucosal melanoma, highlighting the continued need for novel treatment options for these difficult-to-treat patients.

Background: Aboriginal and Torres Strait Islander peoples have a unique place in Australia as the original inhabitants of the land. Similar to other First Nations people globally, they experience a disproportionate burden of injury and chronic health conditions. Discharge planning ensures ongoing care to avoid complications and achieve better health outcomes. Analysing discharge interventions that have been implemented and evaluated globally for First Nations people with an injury or chronic conditions can inform the implementation of strategies to ensure optimal ongoing care for Aboriginal and Torres Strait Islander people., Methods: A systematic review was conducted to analyse discharge interventions conducted globally among First Nations people who sustained an injury or suffered from a chronic condition. We included documents published in English between January 2010 and July 2022. We followed the reporting guidelines and criteria set in Preferred Reporting Items for Systematic Review (PRISMA). Two independent reviewers screened the articles and extracted data from eligible papers. A quality appraisal of the studies was conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement., Results: Four quantitative and one qualitative study out of 4504 records met inclusion criteria. Three studies used interventions involving trained health professionals coordinating follow-up appointments, linkage with community care services and patient training. One study used 48-hour post discharge telephone follow-up and the other text messages with prompts to attend check-ups. The studies that included health professional coordination of follow-up, linkage with community care and patient education resulted in decreased readmissions, emergency presentations, hospital length of stay and unattended appointments., Conclusion: Further research on the field is needed to inform the design and delivery of effective programs to ensure quality health aftercare for First Nations people. We observed that discharge interventions in line with the principal domains of First Nations models of care including First Nations health workforce, accessible health services, holistic care, and self-determination were associated with better health outcomes., Registration: This study was prospectively registered in PROSPERO (ID CRD42021254718)., (© 2023. The Author(s).)

Introduction: Parents of children hospitalised in a burn unit experience psychological trauma and later post-traumatic stress. Aboriginal and Torres Strait Islander families whose child has been admitted to a burn unit encounter additional burdens through a culturally unsafe healthcare system. Psychosocial interventions can help reduce anxiety, distress and trauma among children and parents. There remains a lack of interventions or resources that reflect Aboriginal and Torres Strait Islander people's perspective of health. The objective of this study is to codevelop a culturally appropriate informative resource to assist Aboriginal and Torres Strait Islander parents whose child has been hospitalised in a burn unit., Methods: In this participatory research study, the development of a culturally safe resource will build on Aboriginal and Torres Strait Islander families' experiences and voices, complemented by the knowledge and expertise of an Aboriginal Health Worker (AHW) and burn care experts. Data will be collected through recorded yarning sessions with families whose child has been admitted to a burn unit, the AHW and burn care experts. Audiotapes will be transcribed and data will be analysed thematically. Analysis of yarning sessions and resource development will follow a cyclical approach., Ethics and Dissemination: This study has been approved by the Aboriginal Health and Medical Research Council (AH&MRC) (1690/20) and the Sydney Children's Hospitals Network ethics committee (2020/ETH02103). Findings will be reported to all participants and will be disseminated with the broader community, the funding body and health workers at the hospital. Dissemination with the academic community will be through peer-reviewed publications and presentations in relevant conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Tobacco is the leading preventable cause of morbidity and mortality for Aboriginal and Torres Strait Islander people. Accordingly, the provisions of culturally safe and effective smoking cessation strategies are crucial. While previous research has suggested Aboriginal Health Workers/Practitioners are well placed to provide smoking cessation care, no research to date has explored the workforce knowledge, attitudes and practices in offering best practice cessation care., Methods: A cross-sectional study was conducted among Aboriginal Health Workers/Practitioners from June to September 2021. Descriptive and inferential statistics were conducted to examine participant characteristics, provision of smoking cessation care, and explore the factors associated with smoking cessation care., Results: Out of 1052 registered Aboriginal Health Workers/Practitioners, 256 participants completed the full survey (24.3%). Smoking cessation counseling was always provided by 41.9%; provided some of the time by 42.4%, and never provided by 12.9%. Combination NRT and Quitline referral were always offered by 23.1% and 44.9% of participants, respectively. Those that received training, felt smoking cessation care was part of their role, and were based in Aboriginal Community Controlled Health Organization were significantly more likely to offer best practice smoking cessation care., Conclusion: Aboriginal Health Workers/Practitioners and Aboriginal Community Controlled Health Organizations play a critical role in delivering high quality, evidence based and culturally safe care to Aboriginal and Torres Strait Islander people. Aboriginal Health Workers/Practitioners are well placed to offer smoking cessation care. Ongoing funding and implementation of a targeted smoking cessation workforce with appropriate training and resources are urgently required., Implications: Aboriginal Health Workers/Practitioners are well placed to offer culturally safe, best practice smoking cessation care. However, due to the magnitude and complexity of Aboriginal Health Workers/Practitioners roles, it is challenging for smoking cessation care to be consistently and feasibly integrated into usual care. Acknowledging Australia's National Preventative Health Strategy target of 27% or less Aboriginal and Torres Strait Islander people smoking by 2030, urgent investment and resourcing must be directed to building a skilled workforce to support quitting and maintaining smokefree behaviors, ensuring equitable access to smoking cessation care for Aboriginal and Torres Strait Islander peoples., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: Aboriginal and Torres Strait Islander women deserve improved smoking cessation support. Aboriginal health workers (AHW) and practitioners (AHP) can be central to the provision of culturally safe smoking cessation care (SCC). The objective of this study is to explore attitudes and the perceived role of AHWs/AHPs toward providing SCC to Aboriginal and Torres Strait Islander pregnant women., Method: A mixed-method study using quantitative and qualitative data was conducted among AHW/AHPs in 2021 across Australia. Descriptive and analytical statistics were used to characterise AHWs'/AHPs' attitudes towards SCC and to evaluate the factors associated with perceptions of who is best placed to provide SCC., Results: From the total AHW/AHP workforce, 21.2% (223) completed the survey. Less than half (48.4%) believed that AHW/AHP were best placed to provide SCC for pregnant women. The majority believed that group-based supports (82.5%) and cultural support programs (63.7%) were the best strategies to support Aboriginal and Torres Strait Islander pregnant women to quit smoking., Conclusion: This study highlights the need to enhance SCC offered to Aboriginal and Torres Strait Islander pregnant women. A targeted workforce dedicated to smoking cessation should be resourced, including funding, standardised training, and ongoing SCC support tailored to Aboriginal and Torres Strait Islander pregnant women.

Severe injury and chronic conditions require long-term management by multidisciplinary teams. Appropriate discharge planning ensures ongoing care to mitigate the long-term impact of injuries and chronic conditions. However, First Nations peoples in Australia face ongoing barriers to aftercare. This systematic review will locate and analyse global evidence of discharge interventions that have been implemented to improve aftercare and enhance health outcomes among First Nations people with an injury or chronic condition. A systematic search will be conducted using five databases, Google, and Google scholar. Global studies published in English will be included. We will analyse aftercare interventions implemented and the health outcomes associated. Two independent reviewers will screen and select studies and then extract and analyse the data. Quality appraisal of the included studies will be conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement. The proposed study will analyse global evidence on discharge interventions that have been implemented for First Nations people with an injury or chronic conditions and their associated health outcomes. Our findings will guide healthcare quality improvement to ensure Aboriginal and Torres Strait Islander peoples have ongoing access to culturally safe aftercare services.

Background: Both changes in circulating lipids represented by a validated poor prognostic 3-lipid signature (3LS) and somatic tumour genetic aberrations are individually associated with worse clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). A key question is how the lipid environment and the cancer genome are interrelated in order to exploit this therapeutically. We assessed the association between the poor prognostic 3-lipid signature (3LS), somatic genetic aberrations and clinical outcomes in mCRPC., Methods: We performed plasma lipidomic analysis and cell-free DNA (cfDNA) sequencing on 106 men with mCRPC commencing docetaxel, cabazitaxel, abiraterone or enzalutamide (discovery cohort) and 94 men with mCRPC commencing docetaxel (validation cohort). Differences in lipid levels between men ± somatic genetic aberrations were assessed with t-tests. Associations between the 3LS and genetic aberrations with overall survival (OS) were examined using Kaplan-Meier methods and Cox proportional hazard models., Results: The 3LS was associated with shorter OS in the discovery (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.3, p < 0.001) and validation cohorts (HR 2.32, 95% CI 1.59-3.38, p < 0.001). Elevated plasma sphingolipids were associated with AR, TP53, RB1 and PI3K aberrations (p < 0.05). Men with both the 3LS and aberrations in AR, TP53, RB1 or PI3K had shorter OS than men with neither in both cohorts (p ≤ 0.001). The presence of 3LS and/or genetic aberration was independently associated with shorter OS for men with AR, TP53, RB1 and PI3K aberrations (p < 0.02). Furthermore, aggressive-variant prostate cancer (AVPC), defined as 2 or more aberrations in TP53, RB1 and/or PTEN, was associated with elevated sphingolipids. The combination of AVPC and 3LS predicted for a median survival of ~12 months. The relatively small sample size of the cohorts limits clinical applicability and warrants future studies., Conclusions: Elevated circulating sphingolipids were associated with AR, TP53, RB1, PI3K and AVPC aberrations in mCRPC, and the combination of lipid and genetic abnormalities conferred a worse prognosis. These findings suggest that certain genotypes in mCRPC may benefit from metabolic therapies., (© 2022. The Author(s).)

Circulating lipids or cytokines are associated with prognosis in metastatic castration-resistant prostate cancer (mCRPC). This study aimed to understand the interactions between lipid metabolism and immune response in mCRPC by investigating the relationship between the plasma lipidome and cytokines. Plasma samples from two independent cohorts of men with mCRPC ( n = 146, 139) having life-prolonging treatments were subjected to lipidomic and cytokine profiling (290, 763 lipids; 40 cytokines). Higher baseline levels of sphingolipids, including ceramides, were consistently associated with shorter overall survival in both cohorts, whereas the associations of cytokines with overall survival were inconsistent. Increasing levels of IL6, IL8, CXCL16, MPIF1, and YKL40 correlated with increasing levels of ceramide in both cohorts. Men with a poor prognostic 3-lipid signature at baseline had a shorter time to radiographic progression (poorer treatment response) if their lipid profile at progression was similar to that at baseline, or their cytokine profile at progression differed to that at baseline. In conclusion, baseline levels of circulating lipids were more consistent as prognostic biomarkers than cytokines. The correlation between circulating ceramides and cytokines suggests the regulation of immune responses by ceramides. The association of treatment response with the change in lipid profiles warrants further research into metabolic interventions.

Background: Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20-30% of men with metastatic castration-resistant prostate cancer (mCRPC). Ceramide metabolism may have a role in ARSI resistance. Our study's aim is to investigate the association of the ceramide-sphingosine-1-phosphate (ceramide-S1P) signalling axis with ARSI resistance in mCRPC., Methods: Lipidomic analysis (∼700 lipids) was performed on plasma collected from 132 men with mCRPC, before commencing enzalutamide or abiraterone. AR gene aberrations in 77 of these men were identified by deep sequencing of circulating tumour DNA. Associations between circulating lipids, radiological progression-free survival (rPFS) and overall survival (OS) were examined by Cox regression. Inhibition of ceramide-S1P signalling with sphingosine kinase (SPHK) inhibitors (PF-543 and ABC294640) on enzalutamide efficacy was investigated with in vitro assays, and transcriptomic and lipidomic analyses of prostate cancer (PC) cell lines (LNCaP, C42B, 22Rv1)., Findings: Men with elevated circulating ceramide levels had shorter rPFS (HR=2·3, 95% CI=1·5-3·6, p = 0·0004) and shorter OS (HR=2·3, 95% CI=1·4-36, p = 0·0005). The combined presence of an AR aberration with elevated ceramide levels conferred a worse prognosis than the presence of only one or none of these characteristics (median rPFS time = 3·9 vs 8·3 vs 17·7 months; median OS time = 8·9 vs 19·8 vs 34·4 months). SPHK inhibitors enhanced enzalutamide efficacy in PC cell lines. Transcriptomic and lipidomic analyses indicated that enzalutamide combined with SPHK inhibition enhanced PC cell death by SREBP-induced lipotoxicity., Interpretation: Ceramide-S1P signalling promotes ARSI resistance, which can be reversed with SPHK inhibitors., Funding: None., Competing Interests: Declaration of Competing Interest E.M.K.: Honoraria – Janssen, Ipsen, Astellas Pharma, Research Review; Consulting or Advisory Role – Astellas Pharma, Janssen, Ipsen; Research Funding – Astellas Pharma, AstraZeneca; Travel & accommodation – Astellas Pharma, Pfizer, Ipsen, Roche.B.T.: Grants and personal fees – Amgen, AstraZeneca, Astellas, BMS, Janssen, Pfizer, MSD, Ipsen, Bayer; Personal fees – IQVIA, Sanofi, Tolmar, Novartis, Roche.A.Z.: Advisory Role – Astellas; Honoraria – Astellas; Grants and personal fees – Astra Zeneca, Pfizer; Personal fees – Merck Sharp & Dome, Bayer, Mundipharma, Janssen.I.D.D.: Institutional funding – Pfizer, ANZUP Cancer Trials Group, Bayer, Astellas, Janssen, Movember Foundation, Merck Sharp & Dome; Unremunerated chair of ANZUP Cancer Trials Group.T.S.: Travel – Astra Zeneca.D.R.S.: Grants – Regeneron, Amgen, Arrowhead, Espirion, Novartis; Personal fees – Amgen, Sanofi.A.A.: Consultant – Astellas, Janssen, Novartis; Speakers Bureau – Astellas, Janssen, Novartis, Amgen, Ipsen, Bristol Myers Squibb; Merck Serono, Bayer; Honoraria – Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono; Janssen, Bristol Myers Squibb, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dome; Scientific Advisory Board – Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Pfizer, Telix, Merck Serono; Janssen, Bristol Myers Squibb, Ipsen, Bayer, Merck Sharpe Dome, Amgen, Noxopharm; Travel & accommodation – Astellas, Merck Serono, Amgen, Novartis, Janssen, Tolmar, Pfizer; Investigator research funding – Astellas, Merck Serono, Astra Zeneca; Institutional research funding – Bristol Myers Squibb, Astra Zeneca, Aptevo Therapeutics, Glaxo Smith Kline, Pfizer, MedImmune, Astellas, SYNthorx, Bionomics, Sanofi Aventis, Novartis, Ipsen.A.M.J.: Insitutional funding – Pfizer, Astellas.L.G.H.: Research funding – Astellas; Travel sponsorship – Janssen, Pfizer; Honoraria – Imagion Biosystems. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a "lighter" treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population., Methods/design: MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies., Discussion: MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer., Trial Registration: Australia New Zealand Clinical Trials Registry: ACTRN12618000233224 , prospectively registered 14 February 2018., (© 2021. The Author(s).)