Randomized controlled trials (RCTs) form a cornerstone of oncology research by generating evidence about the efficacy of therapies in selected patient populations. However, their implementation is often resource- and cost-intensive, and their generalisability to patients treated in routine practice may be limited. Real-world evidence leverages data collected about patients receiving clinical care in routine practice outside of clinical trial settings and provides opportunities to identify and address gaps in clinical trial evidence. This review outlines the strengths and limitations of real-world and RCT evidence and proposes a framework for the complementary use of the two bodies of evidence to advance cancer research. There are challenges to the implementation of real-world research in oncology, including heterogeneity of data sources, timely access to high-quality data, and concerns about the quality of methods leveraging real-world data, particularly causal inference. Improved understanding of the strengths and limitations of real-world data and ongoing efforts to optimise the conduct of real-world evidence research will improve its reliability, understanding and acceptance, and enable the full potential of real-world evidence to be realised in oncology practice.

International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing treatments in diverse populations and facilitating the study of rare tumours or specific molecular subtypes. However, a number of challenges continue to hinder the efficient and productive conduct of both commercial and non-commercial international clinical trials. These challenges include complex and burdensome regulatory requirements, the high cost of conducting trials, and logistical challenges associated with ethics review, drug supply and biospecimen collection and management. We propose solutions to promote oncology trial collaboration, such as regulatory reform, harmonisation of trial initiation and management processes and greater recognition and funding of academic (non-commercial) clinical trials. It is only through coordinated effort and leadership from researchers, regulators and those responsible for health systems that the full potential of international trial collaboration can be realised.

Older adults constitute the majority of patients with lung cancer. However, they are under-represented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake. We conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005-2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis. Our study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%). More than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care.

Since the emergence of COVID-19 there have been increasing global concerns about delays and/or discontinuations in cancer care. However, it is unclear to what extent systemic cancer therapy was impacted by COVID-19 in countries with relatively low COVID-19 infection rates. We examined changes in systemic cancer therapy in Australia during the COVID-19 pandemic. We conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between January 2017 to December 2020. We reported monthly dispensing and initiation rates of antineoplastic (chemo-, immuno- and targeted therapy), endocrine and supportive medicines per 100,000 population. We reported monthly discontinuation rates (defined as ≥90 days gap between cancer medicine dispensings) per 1,000 people treated. We used interrupted time series analysis to examine changes during times of increased COVID-19 risk and related public health measures (March, April and July 2020). Between January 2017 and December 2020, 1,011,255 cancer medicines were dispensed to 51,515 people. Overall, there were no reductions in antineoplastic dispensing or initiation during the COVID-19 pandemic. In March 2020, we observed a temporary increase of 39/100,000 (95% CI: 14 to 65/100,000) in antineoplastic dispensing, driven by immunotherapy and targeted therapy. In April 2020, we observed a temporary decrease in chemotherapy initiation (-2/100,000, 95% CI: -4 to -1/100,000) and temporary increase in discontinuation of all antineoplastic medicines (35/1,000, 95% CI: 20 to 51/1,000), but these changes were not sustained. The effective control of COVID-19 in Australia appears to have mitigated the initial impact of COVID-19 on systemic cancer therapy. We observed only small and temporary changes in the use of some cancer medicines early in the pandemic. National Health and Medical Research Council; National Breast Cancer Foundation; Translational Cancer Research Network, supported by the Cancer Institute NSW.

Summary Cancer survivors are increasing as improvements in cancer diagnosis and treatment translate to improved outcomes. As cancer survivors in their reproductive years contemplate pregnancy, it is important to understand the impact of cancer and its treatment on fertility and pregnancy outcomes. Cancer treatments such as chemotherapy and radiotherapy can affect patients’ fertility, and strategies are available to help preserve the future fertility of survivors. The potential impact of previous cancer diagnoses and treatments on pregnancy and maternal and fetal outcomes needs to be assessed and discussed with survivors, with support from materno-fetal medicine specialists and high-risk antenatal services as needed.