While targeted therapies involving driver mutations are promising, they present challenges in the identification and recruitment of patients.

World Cancer Day: Breakthroughs and Challenges for Precision Medicine

2.2.18 -

By Dr. Todd Shuster and Dr. Dana Washburn

February 2, 2018

Each year on February 4, the world’s population unites in the fight against cancer by recognizing World Cancer Day.  The Day aims to raise awareness and education about a disease that touches so many people around the globe, either directly or indirectly through a friend or family member.  With approximately 17.5 million new cases and 8.7 million deaths from cancer each year worldwide[1], clinical research enabling the development of new oncology therapies is critical.  In acknowledgement of this day, Dr. Todd Shuster, Vice President and Global Therapeutic Area Head of Oncology/Hematology, and Dr. Dana Washburn,  Corporate Vice President, Head, Global Medical Services, at Parexel discuss where we are today in the journey of oncology drug development, and some of the key trends in bringing life-changing therapies to patients facing cancer.    

As discussed yesterday, it is essential to know the molecular signature of a cancer so that driver mutations may be identified and effectively targeted.  While targeted therapies involving driver mutations are quite promising, they present some challenges in the identification and recruitment of patients to clinical trials.  Because some of these mutations are quite rare, identifying such patients requires a coordinated effort, as a large number of individuals must be screened. With rare mutations, it may not be sufficient to screen patients just in the United States.  It is necessary to run trials in multiple regions of the world in order to be able to access smaller and smaller subsets of patients, and Parexel’s global reach makes this possible.  

Making it easier to rapidly screen patients, sometimes with a pre-screening blood test to look at DNA fragments circulating in the bloodstream, or identifying ethnic groups more likely to carry specific mutations, are just some of the ways in which we can accelerate enrollment.  Access to cutting edge laboratory testing such as Next Generation Sequencing enables screening patients for hundreds of mutations rather than just a handful, now making it easier to match patients with the correct investigational therapy.

At the same time, with smaller subsets of patients, we may expect to see a greater degree of benefit, impacting the clinical trial design.  For certain drugs undergoing development, it may no longer be necessary to conduct the large randomized phase III trials that had traditionally been the gold standard for regulatory approval and which require years to complete.  In fact, we have seen several drugs recently approved following completion of smaller phase II trials and even a couple of regulatory approvals following phase I studies, something likened to running the “three-minute mile.”  There are also opportunities for novel and adaptive designs for these smaller trials, one way in which we can accelerate clinical development by working with our biostatistics colleagues.  Many of the current studies are also now evaluating therapies in so-called "basket trials."  We recently saw approval of an anti-cancer therapy for the very first “tissue-agnostic indication,” based on a readily available tissue biomarker.

Basket Trials

In basket trials, patients whose different tumors carry the same type of mutation, regardless of the site of origin in the body, are enrolled in a single trial and treated with a single targeted therapy (one “basket”).  This design is possible thanks to the recent progress in identifying cancer driver mutations – see our blog post from yesterday for more information.  However, this design is not quite as straightforward as it may seem.  As one example, patients with BRAF mutated melanoma or lung cancer may respond quite well to a targeted agent, but a patient with colon cancer with the exact same mutation is unlikely to derive the same benefit with the same BRAF targeted therapy.  Based on this example, there are obviously other factors involved which may impact response – other concomitant gene mutations, changes in gene function that are unrelated to the DNA sequence (epigenetics) or differences in the tumor microenvironment.  A good portion of Parexel's ongoing clinical research trials focuses on understanding this resistance and developing new therapies that may overcome it.  For patients, this means that there is hope that additional targeted agents may be effective for them – even if the first agent was not or is no longer effective in controlling the disease. 

Overcoming Challenges

Despite enormous progress, one of the major challenges that we still face in clinical research is recruitment to clinical trials.  With nearly 5,000 cancer therapies undergoing development, and with nearly 2,000 of these already in the clinic[2], we are still faced with a situation where less than five percent of patients with cancer currently enroll in clinical trials.  Parexel is actively involved in developing a patient centric approach, including protocol optimization whereby studies are designed to take into account the fact that cancer patients are not just subjects for a trial, but instead are individuals whose normal, busy and active lives, and the lives of their families, have been abruptly impacted by a diagnosis of cancer and the need for effective treatment.  Looking at clinical research from a patient’s perspective is just one of the ways in which we can make this process a bit easier for those who choose to participate in a trial. 

While there are certainly many challenges in conducting high quality clinical research on a global scale, we have met many of these challenges and have made great strides in bringing tomorrow’s therapies to patients today.  Appropriately, the 2018 World Cancer Day theme is: “We can. I can.”  The theme reminds us that everyone, either collectively or as individuals, can contribute to reducing the global burden of cancer.  Ultimately, our team of dedicated oncologists/hematologists and the hundreds of individuals at Parexel who are involved in the daily work of cancer clinical research all strive to improve, in some way, the lives of millions of patients who have been affected by cancer.  On this World Cancer Day, and all days, we have much to be proud of!

[1]GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388 (10053):1459-1544.

[2]Citeline Trialtrove

Dr. Todd Shuster and Dr. Dana Washburn

We are always available for a conversation.