Why You Should Trust Precision Oncology
Precision oncology and, more specifically, targeted therapies have been under attack since their inception. There’ve been numerous studies and reports claiming that targeted therapies have NOT lived up to expectations and are still inferior to standard therapies.
However, a more detailed look at these so-called ineffective studies reveals many design flaws in their methodologies.
When the data is presented accurately, precision oncology produces significant benefits in both overall survival and reduced side effects for cancer patients.
Problem #1: Using Targeted Drugs Without the Required Biomarker
One issue with many studies involving targeted therapies is the use of targeted therapies without prior testing to ensure the relevant biomarker is present in that patient’s tumour tissue.
While this may seem like a no-brainer, the improper use of targeted drugs can be a key issue in many clinical trials. This issue has been well researched.
What is a Biomarker?
In this context, a biomarker is the oncogenic mechanism that is the target of the drug being used. For example, a biomarker can be a specific genetic mutation like EGFR T790M, or an overexpressed protein like HER2.
Understanding biomarkers is key because they play a major role in whether a targeted therapy will be effective. Lack of biomarkers & Misuse of biomarkers – either failing to use one entirely, or using the wrong kind – are two common flaws in many studies that look at targeted therapies. This leads people to incorrectly assume that targeted therapies do not work nearly as well as they do (when the correct protocols, such as biomarkers, are in place).
Study: Comparing the Use of Targeted Biomarkers vs None in Targeted Therapy Trials vs Standard Therapies
In a meta-analysis of 570 studies (involving 32,149 patients), published between January 1st 2010, and December 31st 2012, Schwaederle et al., (2015) compared response rates (RR), progression-free survival (PFS), and overall survival (OS) between arms that used a personalized strategy (i.e. with the use of a biomarker) versus those that did not.
In other words, they looked at and compared the following groups:
- The use of targeted therapies from trials that did not require the patient to have the targeted biomarker
- The use of targeted therapies from trials that did require a biomarker
- The use of standard therapies
Note: There were several issues with this study, including its short duration; its use of trials that were all only single agent studies; and the fact that there were limited diagnostic and drug options around between 2010 and 2012. Also, phase 2 trials are designed specifically to evaluate the drug’s dosage and safety – not its efficacy.
(A single agent study is a study that only looks at one targeted therapy. However, the most effective targeted therapies require multiple drug combinations to maximize their efficacy. So looking at only one really misses the entire point of how these drugs work. Agent, in this case, simply means drug or therapy.)
However, even with those issues, the study still showed the benefits of precision oncology.
Study Results: A Biomarker-Based Approach Produces Significantly Better Outcomes
Despite these shortcomings, the authors concluded that:
- Personalized strategies (i.e. targeted drugs with a biomarker) were an independent predictor of better outcomes and fewer toxic deaths
- Non-personalized targeted therapies (i.e. there is no confirmed biomarker) were associated with significantly poorer outcomes than cytotoxic therapies (standard chemotherapy), which in turn performed significantly poorer than personalized, targeted therapy.
Problem #2: Type of Biomarker Used
Another issue is the type of biomarker used. For example, was the drug targeting a known genetic oncogenic alteration or an over-expressed oncogenic protein?
Study: The Use of Genomic Biomarkers vs Protein Biomarkers vs None in Targeted Therapy Trials
This issue was addressed in a study by Schwaederle et al., (2016) where the authors performed a meta-analysis and compared Phase 1 targeted trials between January 1st 2011 and December 31st 2013. The study looked at and compared:
- The use of a protein biomarker
- The use of a genomic marker
- The use of no marker whatsoever
Note: This study had similar issues to the previous study, including short study duration; absence of overall survival numbers; limited diagnostics and targeted drugs during that time period; and the fact that phase 1 trials are not designed to determine drug efficacy.
However, again, the trial still showed the obvious benefits of precision oncology.
Study Results: A Genomic Biomarker-Based Approach Produces Significantly Improved Outcomes
The authors concluded that:
- Most Phase 1 trials of targeted therapies did not use a biomarker-based selection strategy.
- The use of a biomarker-based approach was associated with significantly improved outcomes (Response Rate and Progression Free Survival)
- Response rates were significantly higher with genomic alterations (compared to protein biomarkers).
- Studies that used targeted therapies without a biomarker had very few response rates.
It’s pretty easy to see why using a targeted drug for patients who have the biomarker for which that drug was specifically designed will provide better results than standard chemotherapy.
But why was a genomic biomarker found to be better than a protein biomarker?
What Are Genomic Biomarkers?
In oncology, genomic markers are typically early-occurring events that exist in current or potential drivers of the disease. In this sense, the vast majority of tumour cells in the body will maintain and carry the mutations (i.e. genomic marker) for the course of the disease.
In other words: while the actual driver mutations can change – and new mutations can develop throughout the course of the disease – the occurrence of these mutations will remain consistent in all tumour cells.
This is because they occur as a result of faulty DNA repair mechanisms and cannot be fixed. In fact, the definition of a mutation is a change in DNA that is maintained post DNA repair processes.
What Are Protein Biomarkers?
In contrast, Oncogenic protein expression is not nearly as stable. It varies in different tissues, different parts of a tumour, and varies significantly throughout the course of these disease.
Plus, there are many different oncogenic processes that dictate protein expression, including: microRNAs; long coding-RNAs; epigenetic regulation; and processed pseudogenes, to name a few.
Why Genomic Markers are Better Than Protein Markers for Targeted Therapy
Clearly, genomic markers are better than protein markers for targeted therapy because they are consistent, whereas protein markers change. More specifically, genomic markers are consistent throughout the different parts of a tumour, the different tumours in the body, as well as throughout the course of the disease.
Genetic testing is necessary in order to identify the right biomarker(s) involved in your cancer. Using a genomic marker, that remains consistent, is key to your Oncologist choosing the correct targeted therapy. And getting the right targeted therapy is key to you experiencing greater success with your cancer treatment. And that’s what it’s all about.
To summarize, Precision Oncology means using the newest and strongest statistical data to better personalize a treatment strategy. While this does not always mean a targeted agent is going to be a better option than a standard chemotherapy drug, it does require that substantial diagnostic and provable data exist to show this is the case.
Simply put, Precision Oncology provides greater accuracy of diagnosis, and more personalized treatment choices, leading to better survival rates. It is the evolution of cancer care.
A little bit about CTOAM: What Is Precision Oncology?
At CTOAM, we focus on using the most advanced and statistically significant diagnostics for each unique situation. We apply tools such as PET/CT, tumour DNA sequencing, liquid biopsies, and extensive real-time searches of recent peer-reviewed data to provide you with the best statistical chances of long term survival and reduced side effects.
We work with your current treatment team to get you the treatment you need most, now.
See how we help patients like you in our success stories.
You can live longer.
You can have a higher quality of life during treatment.
You can preserve your health rather than destroying it with chemo.
The stats are real and the proof is in: precision oncology is the way of the future!
If you want the best statistical chance of living the longest, with the highest quality of life, register for a Precision Second Opinion with our medical team today.
CTOAM: Now, you really can buy more time.
Schwaederle et al., (2015). Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials. J Clin Oncol;33(32):3817-25.
Schwaederle et al., (2016). Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms: A Meta-analysis. JAMA Oncol;2(11):1452-1459.on May 1, 2018