MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG).

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.

Implementing 'Goals of Care' discussion and palliative care referral for patients with advanced lung cancer: an outpatient-based pilot project.

BACKGROUND: Early involvement of palliative care and advance care planning improves quality-of-life outcomes and survival for patients with advanced lung cancer; however, there are barriers to implementation. AIMS: A single-centre prospective audit reviewing 'Goals of Care' (GOC) form completion and palliative care referrals in an oncology clinic was undertaken with the aim of increasing GOC completion and palliative care referrals for patients with advanced lung cancer. METHODS: Involved physicians attended a communication skills course and then received a communication-priming intervention. Clinicopathological factors associated with GOC completion and palliative care referral were explored. RESULTS: A total of 84 patients receiving palliative treatment for advanced lung cancer was enrolled. Clinicopathological factors, such as poorer performance status, were associated with higher likelihood of GOC completion (P = 0.018) prior to the intervention. Male sex (P = 0.023), absence of sensitising epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement (P = 0.017), type of systemic therapy (P = 0.031) and poorer performance status (P < 0.001) were associated with higher likelihood of palliative care referral. The intervention improved GOC completion (relative risk (RR) 1.29, P = 0.004); however, this was not sustained in a follow-up audit (RR 0.98, P = 0.92) and there was no change in palliative care referral rate (RR 2.5, P = 0.16). Predictors of palliative referral following clinical review included age (RR 1.16, P = 0.001), male sex (RR 14.2, P = 0.02) and poorer performance status (RR 1.76, P < 0.001). CONCLUSIONS: Communication-priming interventions can improve GOC completion for patients with advanced lung cancer. Further investigation is needed to pursue sustainable options for managing this complex patient group and improve guideline-adherence and patient care.

Clinical management of women at high risk of breast cancer.

PURPOSE OF REVIEW: This article reviews the evidence that underpins breast cancer screening and prevention strategies for women at high risk of the disease, with a particular focus on evidence published in the last 18 months. The review is timely because the US National Comprehensive Cancer Network, the UK National Institute for Health and Care Excellence and the American Society of Clinical Oncology have recently updated relevant guidelines that inform practice. RECENT FINDINGS: In the recently published literature, there have been several important findings. A meta-analysis of randomized trials of selective oestrogen receptor modulators (SERMs), along with the first results from the International Breast Cancer Intervention Study II trial, further support the use of SERMs and aromatase inhibitors in the primary prevention of breast cancer. A large observational study has provided evidence that the SERM tamoxifen may be efficacious for breast cancer prevention in women who carry mutations in the breast cancer predisposition genes, BRCA1 and BRCA2. Several observational studies have suggested that contralateral risk-reducing mastectomy, following a diagnosis of breast cancer, may reduce mortality. SUMMARY: Evidence regarding the optimal management of women at high risk of breast cancer continues to evolve and needs to be rapidly implemented into clinical practice.