Optimizing Cancer Care Pathways Through Precision Medicine, RWD

The Role of Real-World Data (RWD) 

RWD relates to patient health status and the delivery of healthcare routinely collected from various sources, including EHRs, product and disease registries, patient-generated health data, and biometric monitoring devices. 

Linking RWD and other information from co-occurring data sets could create study populations that provide generalizable evidence for personalized treatment options. 

According to C.K. Wang, MD, chief medical officer at COTA Healthcare, RWD sources can produce valuable insights into treatments and their outcomes in routine, daily oncology practice. In addition, this data can also play a crucial role in clinical trials. 

RWD can also produce valuable data in terms of treatment sequence. Evidence produced by traditional trials can be limited because it focuses on comparing treatments within a specific line of therapy rather than comparing sequences. 

“A fundamental part of the personalized treatment selection process is understanding treatment-related side effects and/or complications, which are historically established through clinical trials and patient registries,” Wang told PharmaNewsIntelligence. 

“An equally important consideration is quality of life both during and after therapy, but many gaps exist today as clinical trial data do not address all possible patient and clinical scenarios,” he continued. “We believe that real-world data can play a role in filling these gaps.” 

RWD can drive researchers to utilize patient-reported outcomes to capture a broader range of toxicities. Wang stated that real-time patient-reported outcomes enable providers to intervene and manage treatment-related toxicities more expeditiously and help inform future treatment selection and patient management.         

A December 2021 COTA survey found that 83% of oncologists believe RWD is critical to accelerating the development of potentially life-saving cancer drugs and treatments. The findings from the study reinforce the need, by both providers and patients, for cancer care and treatment innovations to be fast-tracked moving forward. 

The Role of Precision Medicine 

While personalized medicine focuses on individualizing treatment options for every unique patient, precision medicine focuses on identifying which treatment approach applies to groups of patients based on genetic, environmental, and lifestyle factors. 

Precision medicine studies an individual’s genes. In cancer care, experts turn to precision medicine for individuals at a higher risk of developing certain cancers or who have failed to respond to a previous treatment option. 

Additionally, precision medicine in oncology expands to include big data, proteomics, transcriptomics, molecular imaging, and more. 

“Precision medicine is already impacting cancer treatment and outcome in two ways,” Wang explained. “First, molecular profiling of a cancer patient can help with risk stratification, which, in turn, can assist oncologists with deciding on the appropriate treatment intensity for a specific cancer.” 

Take, for example, the identification of a “double” or “triple” hit diffuse large B -cell lymphoma, Wang described. This can help a healthcare provider better determine a course of treatment. 

But precision medicine can also help guide specific therapy selection as well. Understanding cancer’s molecular profile enables oncologists to select the best-targeted therapies when available and minimizes unnecessary chemotherapy exposure and toxicities. 

Additionally, biomarkers in the development of precision medicine provide a strategic opportunity for technical developments to improve overall patient health. 

Precision medicine focuses on adjusting treatments based on the use of disease-specific biomarkers. In recent years, the FDA has approved over a dozen specific biomarkers and therapies for cancer treatment. 

The approved biomarkers include programmed cell death ligand-1 (PD-L1), microsatellite instability (MSI), and tumor mutational burden (TMB). 

“Cancer researchers and life science companies are increasingly examining results from broad panel molecular testing to help identify previously ‘unassociated’ biomarkers that may be predictive or associated with therapy response,” Wang stated. “To meet this need, COTA continues to combine real-world clinical datasets with results from broad panel molecular testing.” 

Clinical Trials and Success Rate Challenges 

Still, a major roadblock in cancer care is the clinical success rate. When clinical trials do not enroll enough patients — or a diverse enough patient population — they cannot produce the data necessary to inform personalized and precision treatments. 

Currently, cancer therapeutics have the lowest success rate of all major diseases due to financial barriers, logistical concerns, and the lack of resources for patients and clinicians to support clinical trial enrollment and retention. 

Less than 5% of adult patients with cancer enroll in clinical trials, according to a JAMA Network Open study. Conversely, the majority of adult patients with cancer do not participate in clinical trials, even though 70% of Americans are willing to participate. 

“One of the most pressing challenges that cancer researchers are facing is the call to increase both the volume and diversity of clinical trial participants,” Wang emphasized. “Cancer clinical trial participation rates have remained stagnant and dismally low over the past few decades.” 

Barriers to Clinical Trial Participation 

The most recurrent clinical trial enrollment obstacles include structural and clinical barriers and socioeconomic disparities. 

Patients must have access to a cancer clinic to participate in a clinical trial. Still, transportation, travel costs, access to insurance, and availability of childcare may create a roadblock in trial participation. 

Patients may fail to meet the eligibility criteria even if a trial is available. Often, trials are criticized for having eligibility criteria that are too narrow — sacrificing generalizability. 

Addressing Disparities in Clinical Trials 

Additionally, the COVID-19 pandemic brought to light the longstanding racial and ethnic disparities in clinical trials. A February 2021 JAMA Network Open study revealed that diversity in cancer trials is significantly lacking. 

Data from completed interventional vaccine trials showed that White individuals were overrepresented 77.9% of the time in clinical trials. In comparison, Black or African American individuals were represented only 10.6% of the time, and Hispanic or Latino participants were represented just 11.6% of the time.  

Asian individuals and American Indian or Alaska Native individuals were represented the least amount in the trials, at just 5.7% and 0.4%, respectively. 

“It is critical that clinical trial participants are representative of the general population that a therapy is aimed at treating. Otherwise, proving real-world therapeutic efficacy and tolerance would be nearly impossible,” Wang highlighted.   

Additionally, a 2022 big data analysis performed by Phesi revealed that 48% of US cancer clinical trials have no Hispanic or Latin American representation, and 42% do not include a single Black patient. 

FDA Guidance 

As part of its continuous dedication to fostering inclusivity among clinical trial participants, in November 2020, the FDA issued final guidance to encourage clinical trial diversity from the design to the execution of the tests. 

Aimed at sponsors overseeing clinical trials, the guidance offers four sets of recommendations that sponsors can implement to ensure a diverse participant pool in clinical trials.: 

• Broaden eligibility criteria, avoiding unnecessary exclusions. 
• Design trials to actively achieve participant diversity. 
• Enhance recruitment practices for increased inclusivity. 
• Apply broad eligibility criteria recommendations to drug trials targeting rare diseases or conditions. 

Then, in April 2022, the FDA released a draft guidance to enhance the participation of underrepresented racial and ethnic populations in clinical trials. The guidance urges trial sponsors to establish enrollment targets for these groups at the early stages of clinical development, with a specific emphasis on prioritizing improvements in the area of cancer research. 

By broadening eligibility criteria and actively promoting diversity, the FDA plans to expedite the development of life-saving treatments, bridging longstanding gaps in cancer research and enhancing outcomes for a diverse range of patients globally.