July 2013 Edition Vol.11, Issue 7

Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns

Breast and Lung Cancer Biomarker Research at ASCO:
Changing Treatment Patterns (cont.)

Plasma DNA Testing

Two abstracts at ASCO focused on an alternative to tumor samples for molecular testing. The first study was conducted in breast cancer patients and assessed mutations in the PIK3CA gene.  PIK3CA is mutated in approximately 30% of all breast cancers and 45% of luminal A breast cancers. This study (Beaver J. J Clin Oncol. 2013;31 [suppl]; abstr 11019), conducted at Johns Hopkins, evaluated PIK3CA mutation rates in both formalin fixed paraffin-embedded (FFPE) tumor specimens and pre-surgery plasma samples using polymerase chain reaction (PCR). The results showed both a high sensitivity (92.3%) and specificity (100%) between the FFPE samples and the pre-surgery plasma.  

Similar to the aforementioned study of PIK3CA detection in plasma DNA in breast cancer patients, Mok et al., which reported on the detection of EGFR mutations from plasma DNA of NSCLC patients, showed that when using tissue as a comparator the sensitivity of plasma test was 76% (68 of 89 patients) and the specificity of plasma test was 96% (130 of 135 patients) (J Clin Oncol. 2013:31 [suppl]; abstr 8021).

The study concluded that an EGFR blood test can be used to reliably detect EGFR mutations in plasma and is a potent predictor of survival outcomes. These studies demonstrate that the ability to identify solid tumor mutations in plasma DNA by digital PCR could indicate improvements in diagnostics and advancements in therapeutic decision-making. They also raise the question of how to account for genetic heterogeneity in the tumor or multiple tumor sites when analyzing plasma DNA, as well as whether the plasma DNA test would be as effective if there were discordance between the primary tumor and a recurrence. 

Conclusion

Established biomarkers including ER, PR, HER2, EGFR and ALK hold great potential for the continued development of new targeted therapies and improved treatment decision-making throughout the course of disease. The studies presented at ASCO raise important issues that have repercussions for future treatment decisions: concordance between the primary tumor and a recurrence, acquired resistance, and genetic heterogeneity. All of these issues have the potential to change a tumor’s behavior and sensitivity throughout the course of the disease.

Changes over time may dictate vastly different approaches to treatment that should be considered.

These studies also raise important questions about companion diagnostics – when and how often should the testing occur? Are we using the appropriate testing cut points for HER2, for instance? What is the acceptable and clinically meaningful level of agreement between plasma DNA testing and tumor DNA testing in order to establish plasma DNA as a surrogate tissue for biomarker testing in the case of PIK3CA? When re-biopsying a patient’s tumor, should multiple disease sites be biopsied to best understand discordance and heterogeneity? In many cases no evidence-based treatment approach for patients resistant to initial targeted therapy exists. However, it is clear that the impact of biomarkers on treatment will continue to grow and improve the capacity to provide targeted therapy to cancer patients safely and effectively.

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SIDEBAR: Evolution of Current Predictive Biomarkers

While over 300 biomarkers are currently recommended for use in oncology across all indications, only 25 of them directly influence treatment decisions (predictive and prognostic – guide decision to treat) Predictive biomarkers in many tumor types―including KRAS in colorectal cancer, BRAF in melanoma and EGFR in NSCLC―are now influencing treatment decisions.

Biomarkers for diagnosis and predicting risk of developing disease are common in several disease states, including autoimmune disease, diabetes and cancer. However, biomarkers that are predictive of response to a specific drug therapy are most developed within oncology. Heterogeneity of molecular mechanisms to drive tumor growth establishes the rationale for individualizing treatment decisions and utilizing targeted therapies. The extent and speed with which predictive biomarkers are growing in use in oncology makes this an especially significant therapeutic area.

The five types of oncology biomarkers, their function in oncology and the number (n) of biomarkers in each category are shown in Table 1.

Figure 3a illustrates the rapid growth of the development of predictive biomarkers in oncology in recent years. Figure 3b shows that an increasing percentage of cancer lives are affected by biomarkers. Kantar Health analysis estimates that approximately 800,000 cancer lives are affected by predictive biomarkers, and this number is expected to rise in the coming years as new biomarkers and targeted therapeutics are discovered and established into practice. 

Source: Kantar Health, CancerMPact® Patient Metrics, accessed April 26, 2013

Source: Kantar Health, CancerMPact® Patient Metrics, accessed April 26, 2013

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About the Contributor

Julie Katz, MPH, MPhil, is an Associate Consultant, Clinical & Scientific Assessment at Kantar Health.

Kantar Health is a leading global healthcare advisory firm and trusted advisor to the world’s largest pharmaceutical, biotech, and medical device and diagnostic companies. It combines evidence-based research capabilities with deep scientific, therapeutic and clinical knowledge, commercial development know-how, and marketing expertise to help clients launch products and differentiate their brands in the marketplace.

Kantar Health’s oncology-related offers include CancerMPact® Biomarker Analysis, a global resource based on a thorough review of literature and recently published data that discusses the current and evolving oncology landscape with regard to biomarker segmentation and differences.

If you would like us to act as catalysts for you, contact us at www.kantarhealth.com/contactus.

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Article Comments

Nguyen Nguyen

quotes Hello Ms. Katz, In the article "Breast and Lung Cancer Biomarker Research at ASCO", for breast cancer you wrote "...representing three of 11 unique biomarkers in oncology that are currently recommended to guide choice of drug regimen." Could you please list the names of these 11 biomarkers? Thank you very much, Nguyen quotes

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