A different approach to treatment of rare cancers is needed, with clinical trials that do not need large numbers of patients, said a cancer researcher Professor Ian Olver in an editorial published by the Medical Journal of Australia.
Rare cancers are defined as those with an incidence of less than 6 cases per 100 000 population per annum, but despite the small numbers they account for 30% of all cancer-related deaths. The low incidence of rare cancers makes large randomized trials impractical, which means there are few evidence-based guidelines available for clinicians.
‘Small clinical trials or case series can be used to provide proof and help identify targets for new treatments.’
Professor Olver, Director of the Sansom Institute for Health Research at the University of South Australia, and former CEO of Cancer Council Australia, wrote that "Our approach to clinical trials will need to be different in rare cancers where large randomized trials are impractical."
He wrote that ovarian cancer was a good example of how approaches to rare cancer treatment needed to evolve.
"One feature of common cancers like breast cancer or bowel cancer, where survival has been significantly altered over recent years, is that there is a screening test for early detection. The heterogeneity of ovarian cancer suggests that a population screening test based on a panel of biomarkers will be difficult to achieve."
"Also, the symptoms of ovarian cancer are non-specific — such as bloating; abdominal, pelvic or back pain; bowel menstrual irregularities; and fatigue — so that diagnosis is often late when the disease has spread beyond the ovaries."
However, he noted that there are similarities between ovarian subtypes and other cancers. "These will be helpful in identifying targets for new treatments. For example, high-grade serous carcinoma of the ovary shares similarities with triple-negative breast cancers." Drugs used for metastatic breast cancer are now being trialed in patients with ovarian cancer.
Professor Olver also suggested using small efficacy trials or case series to provide proof of principle for targeted therapies.
"Refinements could be made by interrogating large international digital databases of patient records when the drug is adopted into practice. Other approaches could involve using Bayesian analysis to determine whether the numbers of patients available to be entered in a trial would deliver useful clinical guidance."
"Reassessing research into cancers or cancer subtypes classified as histologically rare may involve finding molecular and genetic similarities across a range of cancers, which suggest that a targeted therapy in one may be successfully trialed in another," Professor Olver concluded.
"This requires national and international collaboration and linking datasets from biobanks and registries."