This is the first in a series of interviews that will be posted to showcase the expertise of the members of our Expert Committees, as well as Special Advisors to Reformulary and Cannabis Standard.
Much of the discussion around cancer, especially for patients, focuses on the body part that’s afflicted – breast cancer, skin cancer, prostate cancer and so on. It’s traditionally been the case that treatments and drugs are tailored to a specific kind of cancer. But what if a treatment could cut across cancer types, improving outcomes for patients with a range of diseases? That’s exactly what an emerging category of drugs, referred to as tumour agnostic therapies, aim to do.
Perhaps the best known example is the first-in-class drug VITRAKVI (larotrectinib), approved in Canada in July 2019. It targets cancers that share the Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, an abnormality found in some rare forms of cancer, including specific breast and salivary gland types, but also less commonly in better known cancers such as small cell lung cancer.
Dr. Bill Evans, a renowned oncologist whose advice we’re fortunate to receive as he is a member of Reformulary Group’s Expert Committee, explained that one of the biggest barriers to advancing these treatments is the difficulty in putting together trials large enough to gain good insight into the efficacy of the new agent. Because the cancers they treat are so rare, what often results is a ‘basket’ trial where patients with little in common are grouped together. “When there’s a 5-year-old with sarcoma and a 75-year-old with lung cancer in the same trial, you lack a standard comparator,” Dr. Evans explained. This makes it difficult to de-construct what the outcome would have been for a patient had they received standard of care instead of a newer drug like VITRAKVI, since there isn’t a large enough patient pool for these rare cancers to compare both treatments.
The result are trials that lack the size and direct comparisons many regulators are looking for. But the data we do have is encouraging – in larotrectinib’s case, three combined studies with 55 participants representing 17 different types of tumours showed a response rate of 81% and progression-free survival (PFS) was 28.3 months.[i]
Progression-free survival is an important way to assess how well a new treatment works – it measures the length of time during and after treatment that a patient lives with the disease but that the disease does not get worse.
Assessing value in cancer drugs is complex and is complicated by the smaller body of evidence for emerging tumour agnostic therapies. In addition to PFS, another metric Dr. Evans suggests paying attention to is the incremental cost effectiveness ratio, a metric that standardizes the cost of cancer drugs in terms of dollars for quality-adjusted life year gained (QALY). A QALY considers both the quality and quantity (length) of life lived – it gives an idea of how many extra months or years of life of a reasonable quality a person might gain as a result of treatment. There isn’t an official guideline for what that should be, but in Canada regulators often look for drugs that cost roughly $50,000-$100,000 per quality-adjusted life year. VITRAKVI costs between $17,967 and $23,955 per month depending on the formulation used, or $216,000 to $287,460 per year. The lack of a standard treatment to compare the new drug to and the rarity of the abnormality targeted by the drug makes it difficult, if not possible, to determine an incremental cost-utility ratio.
With innovative drugs emerging every week, funding decisions are becoming increasingly complex. Public and private payers will need to make decisions on drugs based on small bodies of evidence, and getting the value question right will be critical to ensuring plans’ sustainability. Here at Reformulary Group, we’re fortunate to have experts like Dr. Evans helping us navigate.