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Our very own, Bill Bowman, Clinical Solutions Architect at Prognos Health, sits down for a Q&A discussing targeted oncology therapies in our latest feature piece on Factor This.
Q: Please help set the stage here by discussing why some oncology treatments are considered “targeted”?
A: In recent years, a growing number of FDA-approved oncologic drugs are being classified as “targeted therapies,” that is, they target one or more specific genetic abnormalities that drive the growth and proliferation of cancer cells.
For many commonly occurring cancers — including non-small-cell lung cancer (NSCLC), breast cancer, gastric cancer, colorectal cancer (CRC), certain gynecological cancers, bladder cancer, leukemias, gliomas and many others — different genetic mutations have been proven to play a role in how the tumors develop and thrive. Some examples of gene mutations and biomarkers associated with various targeted therapies can be found in the table below.
Examples of Gene Mutations and Biomarkers with Targeted Oncology Therapies
| Gene mutation or biomarker | Description |
| EGFR | Epidermal growth factor receptor; this is often seen in non-small cell lung cancer (NSCLC) and has various subtypes in various exons (e.g., exon 19 deletion or the T790M mutation) |
| BRAF | A human gene that encodes the B-raf protein; targeted therapies are available to treat melanoma, CRC and NSCLC |
| KRAS | A gene that acts as an on/off switch in the RAS signaling pathway; this presents a therapeutic target for patients lacking a mutation (KRAS-wild type) for various cancers, particularly CRC |
| ROS-1 | A gene mutation or rearrangement occurring in a small percentage of patients with NSCLC |
| PDL-1, PD1 | Refers to the programmed cell death protein; immune checkpoint inhibitor therapies are available for many tumor types where this is expressed |
| TMB | Tumor mutation burden; an emerging biomarker that may play a role in multiple tumors, particularly in NSCLC |
| MSI/MMR | Microsatellite instability/mismatch repair; this refers to a series of mutations seen in many different cancers, including tumors of the gastrointestinal tract and gynecologic malignancies |
| NTRK | Refers to tumors with neurotrophic receptor tyrosine kinase gene fusions; two newly approved targeted therapies are available for this rare mutation that can occur in various tumor types, making it “tumor agnostic” |
| RET | Rearranged during transfection; this is another rare and emerging tumor agnostic biomarker that can appear in various tumors, including NSCLC and thyroid cancer |
Q: How can lab test results help to inform physicians when it comes to prescribing these targeted therapies?
Many targeted therapy options are approved for patients who demonstrate the presence or absence of a particular biomarker or genetic mutation. This biomarker status is validated by clinical lab testing that is ordered by oncologists or other specialists, and is performed on tissue or blood-based biopsies collected from the patient. The results of these tests can then indicate the presence of a genetic abnormality, enabling physicians to select the most appropriate therapy for the patient.
Ongoing scientific breakthroughs are enabling impressive growth in the number of therapies available where clinical efficacy is specifically related to the presence or absence of one or more biomarkers. This is welcome news for patients and the oncologists who treat them, and dramatically changes the way physicians diagnose and treat many different cancers — both solid tumors and liquid tumors (hematological malignancies). Yet, it also adds unprecedented complexity for oncologists and other physicians at the point-of-care.
Q: How can such insights help improve patient outcomes?
A: The emergence of a biomarker-directed approach to cancer treatment — a hallmark of precision medicine — has created an exciting new era for both patients and providers alike. Oncologists can now select biomarker-driven therapies (alone, in combination or in sequence), not only for those patients who are most likely to benefit from them, but also at the most appropriate time in the patient’s treatment flow.
Just as important as prescribing an appropriate targeted therapy to the right patient at the right time is the ability to avoid prescribing it to patients who do not have the appropriate biomarker profile (as verified by clinical lab testing) and are thus unlikely to benefit from the therapy in question. Think about it — as the body of clinical trial data (and ongoing real-world evidence) shows where a particular biomarker-directed therapy is not likely to improve outcomes for certain patients, it does not make sense to subject them to an ineffective and costly treatment, while also risking otherwise avoidable toxicities.
Q: Is lab testing only used by oncologists during a patient’s initial diagnosis and treatment?
A: No. So often in oncology, treatment involves initiating one regimen, monitoring the patient over time to assess whether or not that treatment is effective, and then switching to a different therapeutic option or adding one or more additional agents concurrently. In some cases, a given biomarker-approved therapy is suitable for use as a first-line therapy. In other instances, the same drug(s) is only approved for use as a second- or third-line therapy. Therefore, appropriate timing is essential for both testing and treatment selection.
Similarly, throughout the course of cancer care for a given patient, physicians routinely order other lab tests (including basic blood tests) to monitor the patient’s response to treatment and his/her ongoing health in general. For example, in multiple myeloma a simple lab test for an M-protein spike can indicate whether the patient is relapsing on the current therapy, so the physician can consider switching the patient to a different regimen, if needed.
Meanwhile, additional complications (and potential confusion) can arise for physicians when an existing targeted therapy receives subsequent FDA approval for a different line-of-therapy for the same malignancy or for additional tumor types; or when newer competitors are approved for the same indication(s) and therapeutic target (although clearly such advances create exciting and unprecedented options for oncologists and their patients).
Q: What’s different about biomarker-testing in blood-based biopsies (as opposed to traditional solid-tumor testing)?
A: Another emerging trend in biomarker testing involves the growing use of blood-based testing assays (as an alternative to testing traditional tissue-based biopsy samples) that can identify the presence or absence of targeted, actionable biomarkers. This has a number of advantages for patients and clinicians alike.
For example, drawing blood is less invasive than surgical resection of tissue for lab testing. Further, a blood-based sample can be drawn by a nurse or phlebotomist and is less invasive. In contrast, a tissue-based specimen typically requires that the patient undergo a needle-based or incisional- or excisional biopsy, which must be performed by a specialist, and can be more debilitating and costly for the patient.
In some cases, a pathologist can leverage an archived tissue sample from the patient to test for one or more biomarkers. This often happens when the oncologist needs additional information on a particular biomarker when considering an alternative or sequential course of treatment. However, if an adequate amount of tissue is not available, the patient must undergo another invasive procedure. If the patient declines for any reason, this can create a barrier to appropriate treatment and can adversely affect outcomes.
We expect the use of blood-based biopsy testing will increase over time as more data becomes available demonstrating that sensitivity and specificity rates are comparable to those for more traditional tissue-based specimens and as more biomarkers become amenable for testing with this newer technology.
Q: How can pharma brands support physicians as they make treatment decisions?
A: A: First, brand teams for targeted therapies want to ensure that physicians treating patients with specific tumor types are well educated on the particular biomarker that is relevant for their targeted therapy. Further, our data clearly shows that in tumors where multiple biomarkers play a role, testing rates typically vary for each genetic marker. Physicians often test for certain biomarkers more often than others. This appears to be a function of their familiarity with specific specific abnormalities and the influence of testing guidelines from recognized medical experts. Brand teams with targeted therapies based on newly emerging biomarkers face the additional challenge of positively influencing physicians to begin testing in relevant patients as soon as possible, so that patients with the mutation in question are identified and can be prescribed the appropriate treatment.
Second, once testing for a biomarker is established into clinical practice, brand teams need to ensure that their physician outreach efforts are both relevant and timely. Many oncology brands today achieve this objective via Prognos alerts. These alerts quickly notify pharma brand teams when a given specialist has a “brand-eligible” patient — a patient who can be best served by the therapy in question.
Prognos Health works closely with pharma brand teams to develop and deliver these optimal alerts. This process first requires a thorough understanding of the client’s target patient population, including the optimal sequence of biomarker and other lab testing. We then generate specific profiles based on patient cohorts according to biomarker status and other key patient characteristics, thereby creating alerts identify physicians with de-identified therapy-eligible patients. This is accomplished by leveraging our proprietary data-analytic techniques (which incorporate artificial intelligence, natural-language processing, machine-learning and other modeling modalities) to analyze clinical lab results. and deliver actionable and rapid alerts.
It is important to note that we employ HIPAA-compliant, de-identified patient data, which masks the identity of each patient, yet at the same time allows for pinpointing each physicians who is treating these patients. We are able to alert the pharma brand team on a near-real time basis, enabling the field force to directly act on the information with more targeted, timely outreach to their call-list physicians. In many cases, Prognos data can also uncover providers who are seeing eligible patients, yet are not on the client’s target call list, which allows for enhanced outreach to additional key prescribers.
Our goal is to provide the most relevant clinical and safety information about the right therapy option and at the most opportune time — as the physician is in the process of making key treatment and prescribing decisions for brand-eligible patients in their practices. This level of timed intervention also enhances the likelihood that each patient will achieve an improved outcome.
The objective for Prognos Health is to support pharma brand teams by maximizing their success at reaching out to relevant physicians in a timely manner, creating greater awareness and clinical understanding for the role of relevant biomarker testing, and providing guidance when an appropriate targeted therapy option is available for a patient at the right time. This can ultimately advance improved patient outcomes.
– Bill Bowman, Clinical Solutions Architect, Prognos Health
Q: What are some other ways in which your analysis of biomarker-related lab-testing data can help move the needle in cancer care?
A: For all physicians treating patients with cancer, trying to identify which patients will likely benefit from appropriate targeted therapy is a huge challenge. Fortunately, the prevailing clinical guidelines in oncology, such as those from the National Comprehensive Care Network (NCCN) and American Society of Clinical Oncology (ASCO), provide very specific, data-driven guidance for oncologists and other relevant specialists. These highly-respected guidelines provide specific recommendations for biomarker testing and treatment based on the tumor type and other patient-level characteristics.
Unfortunately, our data often shows that clinicians do not always follow these testing guidelines. For instance, if we track a cohort of de-identified patients with a particular malignancy, we often find that testing is not always performed for one or more specific biomarkers recommended in the clinical guidelines. This signals a missed opportunity for the prescriber, the pharma brand team and ultimately for the patient who .stands to achieve the greatest benefit.
Prognos can help close the loop here. We can leverage our vast repository of clinical lab-testing data, and real-world data and combine this close partnership with pharmacy- and claims-data sources, to identify situations where additional biomarker testing should have been (but was not) carried out.
Finally, we can examine these patterns of sequential biomarker testing at a physician-level for each eligible patient in their practice. Such insights can be eye-opening for pharma brand teams, many of which have preconceived notions about biomarker-/lab testing behavior (assuming that actual practice closely mirrors clinical guidelines, when our real-world data often suggests otherwise). Such insights can be instrumental for any teams preparing to commercialize and launch a promising new targeted brand, and can only help maximize the brand team’s chance for success.
Learn more about how brand eligible patient alerts can enhance your physician-outreach strategy when it comes to complex biomarker-directed therapies in oncology.
About the Author
Bill Bowman is a Clinical Solutions Architect for Oncology at Prognos and has an extensive industry background in oncology and data analytics, with prior experience at a number of leading pharmaceutical companies and consulting agencies.