In November 2017, CMS released a proposed new national coverage position on the use of next generation sequencing in oncology. The final version will be released by February 28, and it will be interesting to see how CMS has triaged the diverse, incoming public comments.
One certain effect is that far more Medicare patients will receive genomic results for uses not currently labeled by FDA or endorsed by NCCN. CMS proposed that if tests like the several hundred gene Foundation One CDx test are used off-label (for example, in kidney cancer), it would require and trigger coverage with evidence development, studying the genes assayed, genetic results, drugs chosen, and clinical drug responses.
However, what might easily be overlooked is that large numbers of Medicare patients with nominally on-label initial testing will get off-label drug suggestions for the first time.
Til Now, CMS MACs Have Channeled and Sequestered Which Patients Get Which Gene Results
Right now, most MACs only pay for genetic tests (like EGFR or KRAS) in those cancers where that gene, if positive, leads to an on-label drug. This means that labs, MACs, and clinicians currently are "coloring within the lines," getting results for BRAF drugs in melanoma, ALK and EGFR genes in lung cancer, and so on.
However, under the proposed NCD, even when the test is initially nominally on-label (like the FMI test in lung, colorectal, and melanoma), many patients will NOT have a positive gene for an on-label drug, but they and their clinicians will have a range of genetic results for off-label drugs. Since the original NGS panel test was on-label (like an FMI CDx test in a lung cancer patient), the NCD doesn't require any CED or suggest what will happen at the MAC level with the panel-based or "passenger" genes that are being reported to the clinician and patient.
But a lot of patients may fall here, especially if they had already screened negative for the common mutations in their cancer (e.g. EGFR/ALK in lung) and the FMI test is used as a fall back test. If MACs provide the drugs, but no clinical data is gathered, we're missing out. If MACs don't provide the drugs, after they have paid for the tests and have supported delivery of the accompanying off label genetic results to the cancer patient, who knows what will happen.
Famously, thousands of patients were screened in an NIH lung cancer trial to identify 200 that actually got drugs and about 20 had objective responses (here).
HER2 Drug Response Depends on Genes + Tissues: Only Human Tumor Type Trials Give Answers (Hyman et al. 2018)
Relevant is a new paper in Nature by Hyman et al. of MSKCC, also profiled by Molika Ashford at Genomeweb. (The paper is open access to view, but not download). In the SUMMIT trial, patients with mutations in HER2 or HER3 were studied across a wide range of cancers - NSCLC, breast, biliary, salivary, and so on. The main conclusion is that only a complex and clinically empirical study of mutations, genes, and tumor type gives a good predictor of drug response. For example, no responses were seen in 16 patients with bladder cancer or in 12 patients with colorectal cancer. The SUMMIT trial, and similar trials underway, are important amplifications of the early lessons we learned in precision oncology (e.g. early lessons that (1) ALK gene-drug pairs seem to work in most cancers, while in contrast (2) BRAF gene-drug pairs work great in melanoma but not in colorectal cancer).*
Note also that in the MOSCATO trial (Massard et al.), 948 patients were biopsied for NGS testing, a possible genetic match found in 411, and 199 received that drug, and 22 had objective responses. They had 12 months PFS, but it's a narrow funnel that eventuated in those 22 patients.
OHSU's Vinay Prasad also wrote about theory and outcomes in basket trials in the February 2018 issue of JAMA Oncology.
For a Nature Reviews Drug Discovery article, 2018/03, on tissue-agnostic oncology drug trials, here.