在肿瘤精准医疗中发挥临床试验的作用

2017-09-18     来源:dddmag     浏览次数:116     收藏

Fourteen years after the human genome project produced the first comprehensive catalog of human DNA, we have reached the point where the unique genetic signature of an individual’s cancer can be used to guide cancer treatment.

This revolution has been a long time coming. Even before the human genome was completed, discovery of the HER2 gene and its role in breast cancer led to multiple targeted therapies for women who have a mutation in the gene.

But one gene is just the tip of the iceberg — with comprehensive genomic profiling available today, we can probe hundreds of genes simultaneously to obtain a more complete picture of each person’s disease and potentially identify new, individualized treatment approaches.

These technologies are helping to realize the vision of precision medicine. Increasingly, oncologists think of tumors not in terms of which organs they inhabit — lung, breast, liver, and pancreas— but in terms of their genomic alterations. Understanding the role of different markers as primary driver mutations in some cancers, hallmarks of metastases or in conferring response or resistance to certain treatments, is critical for the treatment approach and success for patients.

Indeed, the FDA recently made a historic decision by approving an anti-PD-1 immunotherapy for all tumors that have high microsatellite instability (MSI) status, regardless of tissue of origin or where they were located in the body. At the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, data was presented showing responses to a targeted therapy were observed in a wide range of tumors with a specific genetic biomarker, regardless of location within the body. Identifying new genomic biomarkers is the first necessary step in creating new treatment options for patients, but we need more than that. If we want to integrate targeted and personalized treatment approaches into clinical practice, we need to test them in clinical trials.

Only then can we realize the promise of precision oncology.

Clinical Trial Design and Enrollment -- Challenges to Overcome

Clinical trials are the foundation of drug development – they inform us whether a medicine is safe and effective for use and which patients are most likely to benefit from them. Therefore, clinical studies must be designed in such a way  to keep pace with the innovation in cancer genomics and the information gleaned by putting this knowledge into practice.

Programs like the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) now assign treatments to patients based on the genetic alterations found in their tumors, regardless of where those tumors are located in the body. The American Society of Clinical Oncology Targeted Agent and Profiling Utilization Registry (ASCO TAPUR) trial also studies the effects of cancer drugs matched to the genomic profiles of tumors. These clinical studies are helping to ensure that the right medicines get to the right patients.

But while these studies and many others have the potential to expand the treatment landscape for cancer, they will succeed only if patients participate. Patient populations are widely distributed geographically, and trial access or even awareness may be limited outside of academic hospitals. On average, only three to five percent of adult cancer patients participate in clinical trials, and 20 percent of all clinical trials never finish because they are unable to reach their enrollment goals.

Clearly there is a need for improvement to ensure that clinical trials offer scientists, drug developers and regulators the necessary data  to make informed decisions about safety and efficacy. Equally important is that eligible patients have an opportunity to receive cutting-edge therapy based on their cancer’s genomic profile, an area of rising concern as physicians and patients find it hard to navigate the complex and often elusive landscape of clinical trials.

Optimizing trials through genomics

Collectively, many in oncology are working hard to apply solutions that help address these challenges.

Some programs have a suite of offerings that help accelerate clinical trial enrollment by using genomic information to connect patients to trials. For instance, n a case presented at this year’s ASCO Annual Meeting, Foundation Medicine’s SmartTrials Precision Enrollment approach helped a patient participate in a trial by opening up a new treatment site near the person’s home. The new site was activated and approved, and the patient was enrolled within seven days of identification. Today, SmartTrials is being used across multiple clinical trials, to help enhance patient enrollment, which will ultimately accelerate our understanding of potentially transformative medicines for cancer.

Improving clinical trial efficiencies can have a substantial impact on how precision medicine can advance cancer care. Through genomic profiling, we have the opportunity to expand access to clinical trials, connect patients to targeted therapies they are most likely to respond to based  on their cancer’s genomic profile and guide and accelerate the development of new treatments.

Together these continuing efforts by all of us in the global cancer research community will ultimately contribute to significant advancements in patient care.

Melanie Nallicheri joined Foundation Medicine in October 2016 as chief business officer and head, Biopharma. She brings with her more than 25 years of experience in corporate strategy and business development, deep knowledge across healthcare sectors in the U.S. and internationally, as well as experience building advanced analytics capabilities. She has a track record of helping grow businesses and building high-performing teams.

Prior to joining Foundation Medicine, Ms. Nallicheri was senior vice president, corporate strategy and business development, McKesson Distribution Solutions and McKesson Data & Analytics.