It’s our health system, not the science that’s preventing equity of access to precision medicine.
Precision medicine is within the reach of Australian cancer patients.
The system just needs a push in the right direction, according to experts gathered at the inaugural Victorian Precision Oncology Summit held in Melbourne last week.
Personalised molecular testing allows people with cancer to be matched to treatment that targets their specific tumour according to its genomic profile. Not only are survival rates improved, but patients are saved exposure to toxicities and wasted time on treatments that are not likely to work for them.
But in Australia, testing and treatment outside the standard of care are not covered by the PBS, leaving patients and oncologists to work out access as best as they can. Hardly a recipe for equity.
“The problem is not the targets. It’s not the state of science,” Professor David Thomas, the recently appointed Director of the Centre of Molecular Oncology at the University of NSW, told delegates.
“It’s about getting access to the drugs for these patients who would benefit from it, which means more trials because we don’t have an article 71.”
Article 71 is the part of Swiss law (Ordinance of 27 June 1995 on Health Insurance) which requires insurance companies and drug providers to negotiate to cover non-standard treatment where needed.
“In terms of accessing a treatment based on the molecular profile and data analytics, I think we are very lucky in in Switzerland to have this article. That helps us a lot,” said keynote speaker Professor Olivier Michielin, who heads the Centre for Precision Oncology at Lausanne University Hospital in Switzerland.
Professor Michielin described Australia as a “jewel of translational research and patient care”. But in reality, Switzerland is streets ahead in providing equitable access to personalised cancer treatment to its citizens, due to its legal, health and data systems.
In Professor Michielin’s home country, insurance covers both standard of care and off-label therapies in precision oncology. This includes the standard 52 gene hotspot molecular testing panel, as determined by an organ specific tumour board – a process which is also covered by insurance – and a 400 full length gene panel used by the molecular tumour board to recommend individual treatments.
“I think this creates an interesting scenario, because, of course, it’s advantageous for those companies to invest in the analytics if that analytics allows you to have a more rational use of the drugs at the end,” Professor Michielin pointed out.
Patient care is the priority, but precision oncology makes financial sense too, Professor Michielin reminded delegates.
“Sometimes those [predictive] biomarkers will allow you to pinpoint the patient who will not benefit from your therapy. And as the therapies are extremely expensive, the amount you invest in the analytics might be actually well invested, because you’re going to spare treatment costs for many patients as well,” he said.
‘We can do better’
Professor David Thomas, who followed the Swiss professor on the stage, admitted he was “green with envy”. And he wasn’t the only one who found the comparison between systems hard to bear.
“It’s always difficult to hear,” Dr Kortnye Smith, a medical oncologist at Peter MacCallum Cancer Centre, told The Medical Republic.
Dr Smith, who gave delegates a picture of what it’s like for clinicians to try and access molecular testing in Victoria, has researched ways to integrate complex genomic sequencing into cancer therapy and facilitate access to genomics.
“From my point of view, it seems like it would be a reasonably straightforward test to deliver to patients to give improved outcomes. And we’re a long way from being able to deliver that in a way that is equitable for everybody and not determined by which hospital they happen to have their care directed through.”
Lack of public funding for non-standard testing and therapy can put oncologists in a difficult position when their patient is not financially well off, but “all the data certainly tells us that patients would prefer to be told if there are things that are available for them, even if that is at a cost”, Dr Smith told OR.
The price tag on molecular tests is not much higher than for a PET scan, which is covered on the PBS, Dr Smith pointed out. “When cancer drugs can cost $8,000 to $16,000 a month, $3,000 to $5,000 to make sure that we get patients on the right drug does seem like a valuable investment.”
The way Australian advisory bodies evaluate new tests or therapies and make recommendations about funding is part of the problem, she suggested.
“Genomics really hasn’t been able to fit into the way that the boards evaluate what efficacy is. While we can show that patients are living longer after having these tests, it’s [about] the comparator. And it’s hard to provide them with the kind of data that’s required for that,” she said.
The Australian government is currently undertaking a Health Technology Assessment Policy and Methods review, described as “an important opportunity to develop specific reforms to how health technologies are assessed and funded to help ensure that Australia’s subsidy schemes and funding programs continue to meet the needs of Australians into the future”.
Professor John Zalcberg, chair of the Australian Clinical Trials Alliance and editor of TMR sister publication Oncology Republic, has exhorted clinicians and, more importantly, consumers to get onto the website and make submissions before the end of the first consultation round on 6 June 2023.
“Article 71 is in our grasp,” Professor Zalcberg said. “But there needs to be a groundswell of support from the community to say that what we have currently doesn’t provide for the future of medicine and the future of oncology.
“This is a once in a lifetime opportunity for the community to say that what we have is not good enough. We’ve got to do better and we can do better. Lots of countries do better. But we’ve got to convince the people doing this review that the support is there.”
As the CEO of the Australian Genomic Cancer Medicine Centre and of Omico, a not-for-profit set up to match patients with trials, Professor Thomas has been working to connect as many people as possible with treatment within the system we have.
The government backed program started in Victoria and went national in 2019. It now involves 23 cancer centres across the country and patients can be referred from anywhere in Australia. It was expected to reach 3000 people by the end of this year and has already had 7300 referrals.
“Trial matching works,” Professor Thomas said, pointing to slides showing impressive survival data, in some cases doubling. “Imagine if [these results were not for] a model of care, but rather a drug. This magnitude of effect in a terminal population who had exhausted treatment options would get that drug approved in every jurisdiction around the world,” he said.
But while almost 40% of the Omico cohort had biomarkers that would be expected to see those high survival rates, under 6% were getting access to treatment.
“That for me is still an unresolved problem – equity of access; not to the genomics, but to the treatments upon which genomics are predicated,” he told those gathered.
Dr Smith said the program was a very good option for patients, but not all oncologists felt confident about what to do with the test results and the recommendations made by the molecular board, let alone explaining them to patients. Currently, there isn’t even an MBS item number for discussing those results with patients.
“Managing the information and giving the best advice to a patient to make a decision can be really tricky,” she told OR. “And accessing the drug is really challenging. It’s still your job to find access programs or try and get the patient on a clinical trial, to make the right decision in terms of whether they’d be better off on chemo. So there’s still lots of bits and pieces in terms of what is appropriate.”
Dr Smith said education about how genomic testing works would go some way to help.
“There are some types of cancers where it is much more likely that you’re going to find a molecular variant. So when you do get a patient that has, for example, a thyroid cancer, where we know that the rates of mutations are high, you could say this is a patient I’m going to chase down a clinical trial for, or commercial testing, and talk to the patient about the value of it. You’ll know when it’s worthwhile asking for that extra effort to get people where we want them to be.”
To get equity, you need infrastructure
Education was unanimously recommended by forum participants as a way to improve equity of access, for and by clinicians and consumers alike, along with standardisation and centralisation.
Dr Smith told delegates that even standard of care tests are handled and reported differently across laboratories and hospitals.
Of course, data standardisation is complicated, even the Swiss would agree.
“The solution we found was to actually project the data from each hospital into a common vocabulary and that common vocabulary has been determined among us. It took us three years to agree on everything but now we have this common data set that we use,” Professor Michielin told the gathered experts.
Health data is well organised in Switzerland. For starters, electronic health records work. “There is really an opportunity to directly question the general population through electronic patient records, and to be able to complement some of the molecular testing,” said Professor Michielin.
Information collected includes clinical data on efficacy, patient reported outcomes and, importantly, digital pathology images and radiomics.
“Images are really standard. All patients have these images. And if we can base biomarkers on images, in addition to genomic testing, this is, of course, a great opportunity to create a system that will have equity at its roots,” he said.
The country is building an accessible, extremely valuable data system around the analytics from genomics information gathered from both standard and non-standard panel tests, including raw patient data.
And its data-sharing infrastructure allows clinicians to squeeze as much as they can from it, with analysis done by both the pathology department at the university hospitals and bulk RNA sequencing by the Genomic Centre in Geneva.
It also makes it possible to quickly integrate new innovations such as the rapidly evolving field of spatial transcriptomics, which adds spatial information to RNA sequencing.
All of this data is integrated as a reference data set for use by molecular oncology tumour boards, which include bioinformaticians, geneticists, pathologists, and medical oncologists. They consider panel next generation sequencing and use technologies such as data science to make educated decisions about treatment for individual patients, which is then fed back to the referring oncologist and the patient to decide next steps.
The loop is closed by collecting and reporting data from patient treatment and experience.
Thanks to the development of the Swiss Personalized Health Network (SPHN) initiative, the dataset is being expanded to include data from non-university public hospitals and private hospitals around the country. The goal is interoperability – the capacity to compare clinical and genomic data for any patient, being treated anywhere, with the data set.
“We have created a system by which we can gather the material and also at the same time, through flying data managers in a different system, to collect the relevant clinical information, to get what is needed to make the decision through data mining,” Professor Michielin explained.
Over the past seven years, 46% of patients have had off-label treatment administered at their usual location, without needing to travel, and 45% enrolled in a clinical trial.
“So I think we are now pretty happy because we have secured access to every patient to this large dataset, and there is absolutely no cost [to the patient,” Professor Michielin said.
“All of these cases are discussed at a joint tumour board, either at the national or regional level. And thanks to specific articles, like the article 71, we now have the possibility to treat, I think, probably every patient with an off-label drug or a clinical trial. So in terms of accessing a treatment based on the molecular profile and data analytics, I think we are very lucky in Switzerland to have this article. That helps us a lot.”
Back in Australia, access to standard of care molecular testing varies, let alone non-standard of care. We are still seeing pronounced disparities in access to precision medicine, depending on factors including postcode, financial means, whether patients are getting care through the public or private system, the language they speak, the particulars of their tumour, their oncologist, and timing.
“We should use the same ferocity of focus on the system as we do on research,” Professor Thomas told the assembled oncology community.
“We can work with policymakers, government leaders and community leaders to come up with a viable, fundable solution that will solve not just the survival challenges, but those sustainability challenges.
“It shouldn’t be beyond us. If we can actually find a solution to cancer by developing a treatment, surely we can solve the social problems that might stop us from applying it.”
