Oncology in Canada: A Landscape in Perpetual Motion
October 18, 2021
Cancer.
We still haven’t cured it, and the disease continues to devastate individuals and families. But cancer is not what it used to be. Today’s new treatments take medical science to new heights and offer real hope to patients previously considered terminal.
In Canada, four types of cancer continue to dominate: lung, breast (in women), prostate (in men), and colorectal, collectively accounting for about half of all cancer cases.2 Although we still don’t have the final tally for 2020, researchers estimated that 225,800 Canadians would be diagnosed with cancer during that year and that 83,400 would die of the disease.2 This translates to a daily total of 617 cancer diagnoses and 228 cancer deaths. While the number of new cancer cases continues to grow14 — an effect of the country’s increasing and aging population — we can take heart in knowing that survival rates have gone up significantly. At least 63% of Canadians diagnosed with cancer are expected to survive for 5 years or more after a cancer diagnosis, up from 55% in the early 1990s and just 25% in 1940.2
Same diagnosis, different treatment
Traditionally, we have thought of cancer as a war, with a beginning and an end. We fight it. If we’re lucky, we beat it, and if we’re unlucky, it beats us. New treatments are pushing this model to the sidelines, making cancer more of a chronic, manageable condition than a fatal one.
Some patients previously considered untreatable go on to live cancer-free for years, perhaps having to fend off a flare-up now and again. In this sense, the new treatments serve more as peacekeepers than as combat soldiers: they prevent the invader from launching a full-blown attack rather than pushing back enemy troops already on the field.
Of course, these medicines can’t work their magic unless they reach the right patients at the right time. And this is where it gets complicated—and costly. Identifying the right patients for a particular treatment often requires sophisticated screening and laboratory tests, including genetic and tumour tests. The treatments themselves don’t come cheap—a reflection of the enormous R&D investment required to bring them to market. And if cancer is indeed becoming a chronic disease, managed with medications, testing and drug costs will keep rising.
On Target
While an obvious concern to policymakers, the spectre of rising costs is hardly slowing cancer treatment research down. No longer content with the scattershot results of traditional chemotherapy—effective in some, less so in others—researchers and clinicians are increasingly focusing on targeted therapies, which target specific genes and proteins involved in the growth of cancer cells and generally cause fewer side effects.15
At the same time, the cancer pie is breaking up into smaller and smaller pieces. There is no such thing as “treatment for lung cancer” anymore. Current treatments target specific subtypes of the disease based on the characteristics of the cancer cells and the gene mutations driving a particular tumour type. This increasing segmentation has effectively turned some cancers into rare diseases (affecting fewer than 5 in 10,000 Canadians)16 or rare conditions. For example, adenosquamous carcinoma, a rare subtype of lung cancer, falls into this category.
Guided by genes
We have grown accustomed to grouping cancers according to tumour site—breast, lung, colon, and so on—but this tradition is giving way to a classification based on a tumour’s genomic characteristics. The advent of next-generation sequencing (NGS) technologies, which can identify a variety of mutations across many cancer types, has driven this shift.20
To date, researchers have identified four major genomic alterations involved in cancer development.15 They have also discovered that tumours with a similar genomic makeup, regardless of their location in the body, may have more in common than genomically different tumours in the same body site.
ADVANCED CANCER DIAGNOSTICS AND TREATMENT: THE LINGO
The new cancer treatment ecosystem has its own language. Here are some of its key terms.17,18,19
Precision medicine: A treatment approach focused on delivering the right drug to the right patient at the right time, based on biological information (e.g. genes or proteins) to stratify patients.
Personalized medicine: Sometimes used interchangeably with precision medicine, with an added emphasis on customization for each patient.
Biomarkers: A molecule or alteration (e.g. protein, mutated gene) that reveals pathogenic processes or predicts response to a treatment. Common cancer biomarkers include HER2 (breast cancer), AFP (liver cancer), and EGFR (non-small cell lung cancer).
Companion diagnostics: Tests for biomarkers to identify patients who are candidates for precision medicines.
Genetic testing: Medical test that identifies mutations in specific genes. For example, the test for the BRCA1 and BRCA2 genes can help predict the risk of breast or ovarian cancer.
Genomic profiling: Next-generation sequencing techniques enabling rapid characterization of a tumour’s genome to help predict its behaviour. Within breast cancer, the Oncotype DX test can help predict the aggressiveness of a tumour and its response to chemotherapy.
Tumour-agnostic therapy: A drug or other therapy that treats cancer based on the disease’s genetic and molecular features, without regard to the tumour’s location in the body.
This scientific insight has spurred the development of so-called tumour-agnostic therapies—therapies that target tumours with similar genomic profiles, irrespective of location. These pioneering therapies are now entering the market—drugs like Vitrakvi and Rozlytrek, both approved in 2019 by Health Canada for patients with solid tumours with an NTRK gene fusion mutation. 21,22 Such mutations, which can cause two genes to fuse together and produce altered proteins that promote uncontrolled growth of cancer cells, have been identified in breast, colorectal, gynecological, non-small cell lung, and pancreatic cancer, among others. 23
The vast majority of patients with solid tumours do not carry this mutation. But for the small proportion who do, drugs like Vitrakvi can make the difference between, well, life and death. Take Ted Taylor, a patient in B.C. who developed glioblastoma multiforme (GBM) in 2018 and had emergency brain surgery six days after his diagnosis. The prognosis with standard of care—14 months left to live—did not sit well with the single father of three, who immediately began researching his options.
After hearing about Vitrakvi on television, he asked his oncologist about the medication—which was so new the oncologist hadn’t heard about it yet. A second oncologist arranged for Taylor to get preliminary testing done locally. Against all odds, he had the mutation. The oncologist applied to Health Canada to give Taylor special access to the drug, which was shipped from the UK to Vancouver with a stop in Germany. “My dad and I were waiting with the pharmacist at her location,” Taylor recalls. “It came in a special package.”15
Taylor began taking Vitrakvi twice a day in the spring of 2019, initially under Health Canada’s special access program. After two years of treatment, “there’s only a small cavity where the tumour used to be,” he said in a recent Canadian Cancer Survivor Network (CCSN) presentation. “This drug has saved my life, I can unequivocally tell you.”15
Not all candidates for precision medicines respond as well as Taylor, of course. Fortunately, today’s sophisticated genetic tests allow clinicians to identify additional mutations that predict resistance to a therapy, thus sparing the patient from challenging and costly treatment with other potentially less effective therapies.15
“There’s only a cavity where the tumour used to be. I can tell you without any doubt that precision medicine has saved my life.”
Uneven terrain
Triumphant outcomes such as Taylor’s depend on a well-functioning diagnostic and treatment infrastructure, which not all patients can count on. In Canada, responsibility for most biomarker testing falls to hospitals and third-party laboratories.24 Those without the capacity to conduct genetic testing may need to forward samples to other locations, often sending them in batches to reduce costs. All the steps involved in obtaining results—preparing biopsies, pathologist review, delivery to testing site (which could be out of the country), booking the patient to discuss results—take time and resources, and can delay a patient’s access to therapy.
The current system also suffers from a lack of coordination between the decision-makers responsible for companion diagnostics and for drug therapies.17 “Essentially, it’s the postal code that dictates what therapy a patient receives,” says Dr. Calvin Law, chief of the Odette Cancer Centre at Toronto’s Sunnybrook Hospital. “There should be a national plan.”17
For the time being, no such plan exists. A test may be available. Or not. Or the public purse doesn’t cover it. Even after a drug gets Health Canada approval, public funds don’t necessarily cover the corresponding biomarker test. In such cases, the patient may have to take on the cost of the test—or figure out a way to get coverage from private payers or pharmaceutical companies.17
Amid these uncertainties, each province is deploying its own initiatives to improve access to testing. Albertans can count on Alberta Precision Laboratories, a subsidiary of Alberta Health Services, to deliver high-quality diagnostic lab services,25 and the organization’s recent collaboration with Oncology Outcomes (O2) will facilitate the collection of population-level biomarker data.26 The lucky patients recruited to B.C.’s Personalized OncoGenomics (POG) program have access to genomic sequencing that can help inform treatment decisions.27 Quebec’s INESSS has a written process enabling drug companies to include companion diagnostics in their submissions. According to INESSS director Sylvie Bouchard, this bundled review process ensures “that the recommendation to the minister will not delay access to patients who require the test.”17
TESTING IN FLUX: INCOMPLETE COVERAGE OF VITAL BIOMARKER TESTS IN CANADA
While making headway, biomarker testing for cancers targeted by the newest treatments remains inconsistent across the country. 29 As highlighted in the examples below, these uncertainties place an extra navigation burden on patients and clinicians seeking access to the tests. [Note: The access scenarios represent a snapshot in time and may change following publication.]
Sotorasib: The first KRAS inhibitor in Canada, sotorasib targets some subtypes of NSCLC. The CCO’s new diagnostic program covers the KRAS biomarker, but testing availability throughout the rest of Canada remains unclear.
Entrectinib: This tumour-agnostic drug targets 10 tumour types. The current CCO program only tests the relevant NTRK biomarker for thyroid and lung cancer.
Alpelisib: CCO testing for the biomarker (PIK3) that determines suitability for this breast-cancer medication is only covered for lung, colorectal and endometrial cancer.
Cabozantinib: An FDA-approved MET inhibitor that targets a broad range of tumours, this medication has yet to get the green light as a MET inhibitor in Canada, where it is currently approved only for renal cell and hepatocellular carcinoma.
Cancer Care Ontario (CCO), meanwhile, is filling in some testing gaps with the launch of a comprehensive program for cancer testing at diagnosis.28 Factors guiding the process include tumour type, availability of a biomarker test, and availability of testing facilities. As it happens, the program can test for lung cancers targeted by the world’s first KRAS inhibitor, Lumakras, approved by Health Canada in September 2021. While an encouraging development for Ontarians, it raises questions about equitable access throughout the country. In addition, the CCO’s program only covers NTRK testing for limited cancer types, attesting to the patchwork coverage available at the moment.
Physicians, for their part, face the challenges of navigating this patchwork testing landscape and explaining the tests to patients with different levels of health literacy. Recent Canadian consensus guidelines on biomarker testing and treatment may help doctors treating pediatric patients with NTRK fusion cancer,30 but significant gaps still exist. This leaves many patients shouldering a large portion of the access load, forcing some to resort to private options to finance their tests.
A natural fit for patient support programs
Patient support programs (PSPs) originated to fill gaps in the care of patients on specialty pharmaceuticals. As such, they have a built-in flexibility that could be harnessed to facilitate companion diagnostics for cancer.
Some pharma companies are moving in this direction. Bayer Canada’s Fast TRK program provides centralized NTRK gene fusion testing to patients, free of charge, in partnership with LifeLabs and Kingston Health Services.31 In a similar vein, Roche subsidiary Foundation Medicine has partnered with a Canadian PSP provider to test eligible patients for 325 genes using NGS techniques.32 As an example of the program’s value, a test involving a patient with lung adenocarcinoma was able to identify an EGFR mutation, a dozen other mutations, as well as disease-relevant genes without any concerning mutations.33 Called FoundationNavigate, the program also helps doctors enrol patients, who in turn receive assistance with reimbursement navigation. Projecting into the future, one can envision an open-access PSP, subsidized by a consortium of pharmaceutical companies or perhaps by governments, devoted to navigation and execution of companion diagnostics. An area to watch.
A Holistic Vision
In tandem with the revolution in cancer diagnostics, clinical trials are finding new ways to evaluate the success of a drug. While overall survival remains the gold standard, evolving endpoints such as pathological response, metastasis-free survival, and time to treatment failure may have more clinical significance in particular scenarios.34 For example, one-year survival carries the greatest significance in cancers with a poor prognosis, while event-free survival can help tease out events of interest such as metastases or fractures.34
Patient-reported outcome measures (PROMs), meanwhile, will take on added importance as cancer shifts toward a chronic disease. As US-based clinician Atul Awande noted in his book Being Mortal, “medical care should focus on well-being rather than survival,” and PROMs put well-being at the forefront.35 Building on this theme, the authors of a 2019 commentary in Nature Reviews Drug Discovery noted the opportunity to reconsider traditional approaches to health technology assessment and put more emphasis on PROMs.36 In their view, failing to do so could lead assessors to undervalue new treatments.
Insights from PROMs can inform the development of next-generation drugs that give patients what they most value beyond merely surviving. From a systems perspective, PROMS also serve as a rich source of real-world evidence (RWE), which in turn can play into reimbursement decisions. In line with this vision, Dr. Parneet Cheema, Medical Director of Oncology at William Osler Health System in Toronto, is spearheading a multicentre observational study called PALEOS that will collect data on patients with lung cancers associated with specific gene mutations.37 If all goes according to plan, the data could help support outcomes-based agreements (OBAs) that facilitate access to precision medicines.
Not to be discounted, real-world trials can help achieve equitable representation in outcomes data. Elderly patients, who represent roughly two-thirds of cancer cases, comprise only 20 to 30% of oncology trial subjects, and women accounted for only 38% of participants in trials that led to cancer drug approvals in 2018.38 The impact of gender and ethnicity on biomarker mutation status makes it especially important to correct such imbalances.38
Full circle
For all its power, research alone won’t solve the cancer treatment puzzle: a complete circle of care begins with screening. We know that it works: breast cancer mortality drops by 21% in women aged 50 to 69 who undergo regular mammographic screening,39 and a US study linked half of the decline in mortality from colorectal cancer between 1975 and 2000 to screening programs.40
That said, we have yet to figure out the optimal level of population-level screening: broad screening carries the risk of overdiagnosis and unnecessary interventions, while restricted screening can lead to missed diagnoses and delayed treatment. Perhaps the answer lies in better screening, as advocated by Azra Raza, a professor of medicine at Columbia University. “Why aren’t we using the latest technology to try and identify cancer at its inception?” she says.41 She anticipates that future technology will enable us “to find the earlier footprints of cancers, and that along with that revolution will come better treatment options.”
“Why aren’t we using the latest technology to try and identify cancer at its inception? ”
Most current screening programs in Canada cover breast, colorectal, and cervical cancer. Ontario and B.C. have lung cancer screening programs in place, and a pilot project in Quebec is offering lung CT scans to people aged 50 years or older.42 Concerns about the potential harms of prostate cancer screening, which include overdiagnosis and overtreatment, have led some jurisdictions to opt out of population-level screening for this type of cancer.43
Instead of piecemeal genomic testing, some experts recommend testing the whole genome, which could do double duty as a screening tool and treatment decision aid for patients with existing cancers. “There are too many biomarkers to do individual tests anymore,” notes Nathan Pennell, a medical oncologist at the Taussig Cancer Institute. “It costs a lot more to do multiple tests and bill for each individually than it does to do one [whole genome] NGS test… NGS should absolutely be the standard of care.”38
Sequencing the whole genome used to cost millions, but companies are now offering the service for a few thousand dollars,29 bringing Dr. Pennell’s vision into the realm of possibility. Even so, as life expectancy continues to increase for cancer patients, with some patients remaining on targeted therapies for decades, costs are bound to rise.
This radical shift in cancer treatment philosophy raises uncomfortable questions: how many new drugs can the health system bear? How good do they need to be to justify their costs? How to ensure equitable access to these drugs across a country as spread out as Canada? Are these therapies providing the outcomes that patients want? Our country needs a plan. In the meantime, patients can take their cue from GBM survivor Ted Taylor, who urges patients to arm themselves with information, get tested, and play an active role in their own treatment. “Research and become your best advocate,” he says.
One way or another, things are about to get more interesting. It’s never a good time to get cancer, but today’s patients have life-changing options that never existed before—and they keep getting better. Stay tuned.
References
Canadian cancer statistics. Government of Canada. https://cancer.ca/en/research/cancer-statistics
Cancer statistics at a glance. Canadian Cancer Society. https://cancer.ca/en/research/cancer-statistics/cancer-statistics-at-a-glance
Emergency situation facing Canadians in light of the COVID-19 pandemic. Canadian Cancer Society, April 2021. https://sencanada.ca/content/sen/committee/432/SOCI/Briefs/CanadianCancerSociety_e.pdf
PMPRB Meds Pipeline Monitor 2020. https://www.canada.ca/content/dam/pmprb-cepmb/documents/npduis/analytical-studies/meds-pipeline-monitor/2020/MPM-2020-en.pdf
Approved in 2020: drugs for human use. Government of Canada. https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2020/approved-2020-drugs-human-use.html
Global oncology innovation continues despite COVID-19 pandemic. IQVIA, July 3, 2021. https://www.iqvia.com/newsroom/2021/06/global-oncology-innovation-continues-despite-pandemic-global-rd-pipeline-reached-3500-new-drugs-in-2
Ray T. FDA approves record number of precision oncology drugs in H1 2021. Precision Oncology News, July 21, 2021. https://www.precisiononcologynews.com/cancer/fda-approves-record-number-precision-oncology-drugs-h1-2020#.YTiiv99E02w
Global oncology precision medicine market (2020 to 2030). Intrado Global Newswire, Jan. 5, 2021. https://www.globenewswire.com/en/news-release/2021/01/05/2153331/28124/en/Global-Oncology-Precision-Medicine-Market-2020-to-2030-Analysis-and-Forecast.html
Oncology medicines in Canada 2010-2019. PMPRB, Oct. 2020. https://www.canada.ca/content/dam/pmprb-cepmb/documents/reports-and-studies/chartbooks/OncologyChartbook-2010-2019-EN.pdf
PMPRB Annual Report 2019. https://www.canada.ca/content/dam/pmprb-cepmb/documents/reports-and-studies/annual-report/2019/pmprb-ar-2019-en.pdf
Canadian Cancer Society Statistics 2019. https://www.newswire.ca/news-releases/lung-cancer-patient-care-the-conference-board-of-canada-cites-the-quebec-heart-and-lung-institute-as-a-model-even-as-its-labs-are-threatened-811392455.html
Haslem DS et al. A retrospective analysis of precision medicine outcomes in patients with advanced cancer reveals improved progression-free survival without increased health care costs. J Oncol Pract 2017; 13:e108.
Lung cancer patient care. Cision, March 17, 2021. https://www.newswire.ca/news-releases/lung-cancer-patient-care-the-conference-board-of-canada-cites-the-quebec-heart-and-lung-institute-as-a-model-even-as-its-labs-are-threatened-811392455.html
Cancer statistics. Canadian Cancer Society. https://cancer.ca/en/research/cancer-statistics
Tumour agnostic treatments and the future of specialized medicine. A CCSN presentation, May 27 ,2021. https://www.youtube.com/watch?v=RAkItUeZ23Q
Drugs for rare diseases. CADTH, Feb. 11, 2016. https://www.cadth.ca/drugs-rare-diseases-evolving-trends-regulatory-and-health-technology-assessment-perspectives
A review of precision medicine companion diagnostics in Canada. CCSN, Nov. 2020. https://survivornet.ca/wp-content/uploads/2021/01/A-Review-of-Precision-Medicine-Companion-Diagnostics-in-Canada.pdf
Personalizing your breast cancer treatment through genomics. Genomic Health. https://www.mybreastcancertreatment.org/en-US/LearnAboutOncotypeDX/WhatIsGenomicTesting
Tumor-agnostic therapy. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tumor-agnostic-therapy
Behjati S. What is next-generation sequencing? Arch Dis Child Educ Pract Ed 2013;98:236.
Health Canada approves Rozlytrek. Cision/Roche, April 28, 2020. https://www.newswire.ca/news-releases/health-canada-approves-rozlytrek-r-entrectinib-for-ntrk-gene-fusion-positive-solid-tumours-in-locally-advanced-or-metastatic-patients-1--874636249.html
NTRK-fusion positive cancers. Genentech. https://www.gene.com/patients/disease-education/neurotrophic-tyrosine-receptor-kinase
Birch A. Biomarker Testing. Sentrex Academy presentation.
Alberta Precision Laboratories website. https://www.albertaprecisionlabs.ca/
Cheung W. LinkedIn announcement. https://www.linkedin.com/posts/winson-cheung-3ba8812_collaboration-data-biomarkers-activity-6805912607464194048-K-Bz/
Personalized OncoGenomics Q&A. BC Cancer. http://www.bccancer.bc.ca/about/news-stories/stories/personalized-onco-genomics-(pog)-q-a
Comprehensive cancer testing at diagnosis—wave 2 implementation. Memo to regional cancer programs. Cancer Care Ontario, Aug. 3, 2021.
20Sense original research.
Perreault S et al. Canadian consensus for biomarker testing and treatment for TRK fusion cancer in pediatric patients. Curr Oncol 2021;28:346.
The Fast TRK testing program. Bayer Canada. https://www.fasttrk.ca/en
Foundation Medicine (Roche) support services. https://www.foundationmedicine.ca/SupportServices.aspx
Companion diagnostics associated findings. FoundationOne sample report. https://images.ctfassets.net/w98cd481qyp0/2pusoGEB1tZXWHYL3vlDnv/8392c7cfa1ebf36f9098c936324a73e3/F1CDx_NSCLC_CDx_Elevated_TMB.pdf
Evolving endpoints in oncology. IQVIA, July 8, 2021. https://www.iqvia.com/en/insights/the-iqvia-institute/reports/evolving-oncology-endpoints
Being Mortal. Wikipedia. https://en.wikipedia.org/wiki/Being_Mortal
Calvert M et al. Harnessing the patient voice in real-world evidence: the role of patient-reported outcomes. Nat Rev Drug Discov 2019;18:731.
Pan-Canadian Lung Cancer Observational Study (PALEOS). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04706754
Al-Wattar D. End-to-end personalization in oncology. June 6, 2021.
Breast cancer screening in Canada. CPAC 2017. https://www.partnershipagainstcancer.ca/wp-content/uploads/2019/01/Breast-Cancer-Screen-Quality-Indicators-Report-2012-EN.pdf
Sauber A. The impact of screening on colorectal cancer mortality and incidence: has it really made a difference? Dig Dis Sci 2015;60:681.
Cancer research is an ‘embarrassment,’ must switch focus to early detection: oncologist. CBC The Current, Jan. 23, 2020. https://www.cbc.ca/radio/thecurrent/the-current-for-jan-23-2020-1.5437375/cancer-research-is-an-embarrassment-must-switch-focus-to-early-detection-oncologist-1.5437378
Lung cancer screening demonstration project. Government of Quebec. https://www.quebec.ca/en/health/advice-and-prevention/screening-and-carrier-testing-offer/lung-cancer-screening-demonstration-project
Prostate cancer. Cancer Care Ontario. https://www.cancercareontario.ca/en/types-of-cancer/prostate
Cheema PK et al. Consensus recommendations for optimizing biomarker testing to identify and treat advanced EGFR-mutated non-small-cell lung cancer. Curr Oncol 2020;27:321.