We are at a turning point in the treatment of cancer.

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.    

It is no exaggeration to state that we are currently at a turning point in the treatment of cancer.  We have much to be excited about in terms of the recent progress that has translated into major improvements in the lives of patients dealing with cancer.  However, we also recognize that the promises of new therapies are not realized for everyone – there remains much work to be done to expand upon recent advances.

Many of the remarkable advances that we have seen are the result of an explosion of knowledge and understanding of the genetic and immunologic basis of cancer.  One outcome of this breakthrough is the approval of more than 30 new agents or new indications for treatment of cancer over the past calendar year.  There are two areas in particular that have yielded the most encouraging results: targeted therapy, or so-called precision medicine, and immunotherapy.

Targeted Therapy

In the past, chemotherapy drugs impacted cancer cells and normal cells indiscriminately, resulting in serious toxicities.  The treatments exerted their beneficial effects only because cancer cells had a diminished capacity to recover from those toxic effects when compared with normal cells.  Today, we can identify specific driver mutations in a significant number of patients.  For these patients, specific changes in the DNA sequence are responsible for the malignant behavior of cancer cells: uncontrolled growth, invasion into surrounding tissues and spread.  Identification of these genetic abnormalities in cancer cells allows for targeting unique mutations with therapies that are not only much less toxic but also much more effective.  Examples of such therapies span a variety of tumor types, such as EGFR-mutated lung cancer, BRAF-mutated melanoma, FLT3-mutated leukemia or BRCA-mutated ovarian cancer, to name just a few.  It is no longer sufficient to simply know the tissue type of cancer. It is essential to know the molecular signature of the cancer so that these driver mutations may be identified and effectively targeted.

Immunotherapy

The other area generating extraordinary and justifiable excitement in Oncology/Hematology clinical research is immunotherapy.  Development, growth and spread of cancer represent, at some basic level, a breakdown in the normal process of immune surveillance whereby our natural defenses against cancer malfunction.  A new understanding of how cancer cells themselves can disable this immune response has led to development and approval of several agents that can reactivate the immune system.  These immune checkpoint inhibitors, which “take the brakes off” of the immune system, have enabled a meaningful subset of patients with advanced cancers to do well for extended periods of time – a reality that we could have only imagined 10 or even five years ago.  Much of Parexel’s current research focuses on new combinations involving immunotherapy with the goal of enhancing efficacy so that more patients may enjoy the durable benefits that have been seen in some individuals.  These combinations may be with other types of immunotherapy, such as cancer vaccines, or with targeted agents, as described above, or with more traditional chemotherapy and/or radiation therapy. 

Cellular and gene therapy, another form of immunotherapy whereby our own immune cells can be genetically reprogrammed to recognize cancer cells (e.g., CAR-T cell therapy) is an area where Parexel has developed recent expertise.  While this approach has generated a high level of interest in the media because of its dramatic clinical benefits in refractory lymphoma patients and pediatric leukemia patients, it poses some unique challenges: capabilities at a limited number of cancer centers, regulatory issues and logistics related to collection and transport of cellular products, and clinical recognition and management of specific toxicities.  However, given the recognized potential to transform the lives of cancer patients in the coming years, Parexel is committed to developing and delivering the clinical research expertise necessary to overcome these challenges in the clinical investigation of cellular and gene therapy.

It is an incredibly exciting time in the field of Oncology/Hematology, and as we mark this upcoming World Cancer Day on February 4, there is good reason to be hopeful.  The commitment to understanding the molecular and the immunologic basis of cancer has led to an abundance of promising therapies, many of which have only recently entered into the clinic.  In our next blog, we will discuss how we are adapting clinical trial processes and designs to optimize development of these paradigm changing therapies.  More to come tomorrow!

[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.