The Promise of Pembrolizumab

But what does the recent approval of this immunotherapy mean for pathology labs?

October 2nd saw the approval by the US Food and Drug Administration (FDA) of an eagerly-anticipated immune therapy for advanced non-small cell lung cancer (NSCLC), pembrolizumab, in conjunction with its companion diagnostic, the PD-L1 IHC 22C3 pharmDx test – the first test designed to detect PD-L1 expression in non-small cell lung tumors – making this a pretty big development for pathologists. Already approved for the treatment of melanoma, the therapy is a PD-1/PD-L1 pathway blocker, a mechanism that has been shown to be effective in destroying cancer cells. How? Recent research has shown that blocking the PD-L1 protein on the surfaces of cancer cells, or its corresponding receptor PD-1 on immune cells, may allow patients’ immune systems to detect and destroy cancer cells and it’s on this basis that pembrolizumab exerts its effects.

Another item now added to the precision medicine toolkit against cancer, the approval is welcome news for oncologists and patients, and it further highlights the new role of the pathologist – as a true partner to the oncologist. This changing role is a positive development for the profession, which is struggling to gain recognition amongst the public and its healthcare peers, but with this change comes something that most labs will struggle to absorb – an increased workload. We spoke with Kenneth Bloom, Clarient’s chief medical officer, about what this recent development means for pathologists and about being selected as one of three reference laboratories in the US to conduct pembrolizumab’s companion diagnostic test.

What does the approval of pembrolizumab and its companion diagnostic mean for pathologists?

Pembrolizumab is a member of a new class of emerging therapies known as immunotherapies, but it’s also a “precision drug.” Only patients who express the PD-L1 biomarker on the majority of their lung cancer tumor cells demonstrate improved outcomes with pembrolizumab. That means oncologists will rely heavily on pathologists to help them select patients to receive the drug. The companion diagnostic provides a better understanding of the tumor and its environment and helps us determine whether or not a patient expresses sufficient PD-L1 to be a good choice for pembrolizumab treatment. This approval broadens the treatment options for patients, and helps ensure they’re receiving the best available therapy.

How did Clarient’s pathology laboratory become one of three in the US certified to perform the companion diagnostic test?

We acquired the kit – which was investigational at the time – and went through a rigorous training and certification process. Our pathologists were tested on 45 cases over two days to ensure that they could accurately interpret slides and get reproducible results on patient samples, based on the 50 percent detection cut-off for PD-L1. Any lab could undergo the same process, but we believe that our history in companion diagnostic testing and our pathologists’ deep domain expertise in cancer pathology contributed to our selection as a national reference laboratory for pembrolizumab.

Do oncologists fully understand when to use, and how to interpret, the PD-L1 test?

Not always. Because our understanding of cancer changes every day, it’s often a battle for oncologists to keep up with the latest test and treatment options. There are different PD-1 therapies and PD-L1 tests on the market, and it’s hugely important for oncologists to order the right tests for their drugs of choice, as each companion diagnostic is different. Pathologists need to partner with oncologists to ensure that the right assay is being used and the result interpreted appropriately. As a reference lab, if a pathologist or oncologist sends us a tumor biopsy without knowing which drug might be best suited for the patient, we can explore the possible options.

Might increased testing volume and companion diagnostic assay pricing exclude smaller labs from conducting these tests?

As precision medicine advances and more of these drugs become available, it will be harder for smaller labs to keep up. Taking on a companion diagnostic means acquiring the kit, training lab personnel, deep pathology expertise to assess slides appropriately, and the infrastructure to efficiently process a variety of tests – a heavy resource burden. Luckily, most of a pathologist’s job doesn’t require a rapidly growing arsenal of equipment and personnel, so there’ll always be a place for smaller labs to perform routine pathology services. For companion diagnostics and emerging diagnostic technologies, this is where larger labs comes into play; we have the capacity, technicians, pathologists, equipment, resources and expertise to provide access to the critical tests necessary in the era of precision medicine. We make sure that every patient can access tests that ensure the most appropriate therapy, even if their local hospital lacks the resources.

As precision medicine continues to grow, how can pathology services keep up?

I think centralizing experts is the answer to providing expert pathology services. Centralization can be physical or virtual, providing access to labs that can run the gamut of companion diagnostic kits. Precision medicine rests on the need to obtain much more than a positive/negative test result; it relies on a detailed analysis of the tumor – what it looks like, what’s driving it and how it interacts with its environment. As targeted healthcare leads us down the road to a broader range of potential treatments, physicians will need scalable labs to meet the growing demand for companion diagnostics and other complex laboratory tests.