Issue 43 / 9 November 2015

DEVELOPMENTS in the way cancers are classified are paving the way to evidence-based therapies for rare cancers, which leading researchers are hopeful will have a “fairly significant” impact on cancer mortality in Australia.
Professor David Thomas, director of the Kinghorn Cancer Centre at the Garvan Institute of Medical Research, said rare cancers had been “systematically neglected” in clinical trials because trials and funding had traditionally focused on common cancers defined by their anatomical classifications.
“Molecular classifications are turning what we thought of as monolithic common cancers into a variety of subgroups, each with their own specific therapy and, paradoxically, they’re creating opportunities to think differently and perhaps even develop treatment that might work for rarer cancers as well”, Professor Thomas told MJA InSight.
Professor Thomas said clinical trials and disease management needed to evolve to make the most of these new opportunities.
“In principle, with the tools and drugs that we have, if we could use them effectively and provide access for patients with rare cancers, I think we could have a fairly significant impact on the bottom line of mortality from cancer in our country.”
Professor Thomas’s comments coincide with an MJA editorial on rare cancers, published online today, by Professor Ian Olver, head of the University of SA’s Sansom Institute of Health Research. (1)
In his editorial, Professor Olver said an audit published by Cancer Australia in 2014 had shown that more than 80% of cancer research funding “went to haematological cancers and only five solid cancers (breast, colorectal, prostate, melanoma and lung), yet rare cancers account for 30% of cancer deaths”.
Rare cancers are defined as having an incidence of fewer than six cases per 100 000 population per annum.
Professor Olver outlined how the genetic subtyping of ovarian cancer — defined as an uncommon cancer with an incidence of 10 per 100 000 population per annum — was revealing similarities between cancers that could guide the management and treatment of rare cancers.
He wrote that poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) that had been trialled in patients with metastatic breast cancer who carried mutations of the BRCA1 or BRCA2 genes were now being trialled in patients with ovarian cancer, including those with BRCA1 or BRCA2 mutations.
Professor Olver said that reassessing research into cancers or cancer subtypes classified as histologically rare “may involve finding molecular and genetic similarities across a range of cancers, which suggests that a targeted therapy in one may be successfully trialled in another”.
Associate Professor Clare Scott, medical oncologist at the Royal Melbourne and Royal Women’s hospitals and laboratory head at the Walter and Eliza Hall Institute of Medical Research, said patients diagnosed with a rare cancer were often faced with a “complete lack of evidence-based options”.
“The thing with rare cancers is that many of them aren’t part of a research or a treatment program and [these patients] risk being lost between the cracks”, Professor Scott told MJA InSight.
However, she said that by using next generation sequencing technology it might be possible to match a tumour to a treatment in an “impressive proportion” of rare cancers.
While there were many rare cancers where a match could not be found, each time one was found “you are uncovering more of the puzzle and making a real difference to patients”.
Professor Scott, who is leading research into PARP inhibitor resistance, said it might be possible to identify the “driver gene” in 30%‒40% of rare cancers.
“Studying rare cancers and the archetype of cancers with the BRCA1 or BCRA2 mutation has led us to understand the genome repair defect and the role of PARP inhibitor therapy”, Professor Scott said, adding that this approach might also be relevant to patients without the inherited mutation.
She said PARP inhibitors were proving to be efficacious in subsets of pancreatic, prostate and gastric cancers, in which genetic markers for genome repair defects had been identified.
Professor Scott is waiting for ethics approval to enrol patients with rare cancers in an upcoming national trial, which will use genomic testing to try to match these patients with potential treatments in existing Phase II clinical trials targeting common cancers.
“We are trying to piggyback off mechanisms that are still being developed in the common tumour streams”, she said, adding that this would offer a more rational and targeted approach than the current “best guess” strategy for rare cancers.
Rare cancers is the theme at next week’s Clinical Oncology Society of Australia’s annual scientific meeting. (2)
(Photo: Tyler Olson / shutterstock)

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