Patient-reported outcomes are playing a growing role in cancer research and are poised to become an important part of regulatory review in drug development-and even routine clinical cancer care.
Patient-reported outcomes (PROs) are playing a growing role in cancer research and are poised to become an important part of regulatory review in drug development-and even routine clinical cancer care, according to experts at the American Society of Clinical Oncology (ASCO) Annual Meeting 2016, held June 3–7 in Chicago.
During a June 6 session entitled “Integrating Patient-Reported Outcomes into Cancer Clinical Trials and Regulatory Review,” experts discussed PROs, which are measures of patients’ symptoms and physical, cognitive, social and emotional functioning, and health-related quality of life, that are obtained via self-administered questionnaires or structured interview questions.
In research settings, there are indications that PROs might improve early detection of side effects.
Basch“Early data suggest PRO [measures] might also enhance our ability to discriminate adverse events between study arms,” reported Ethan Basch, MD, MSc, of the University of North Carolina at Chapel Hill, a leading researcher in PRO assessments of adverse events among cancer patients.
In one study, the number of adverse events found to be statistically-significantly different between treatments was three times larger when adverse events were measured using PROs instead of traditional clinician-driven adverse-events reporting, Basch noted.
Incorporating PROs in drug development
Such findings have prompted the FDA to take a serious look at how best to incorporate PRO assessments of symptomatic adverse events in drug development, said Paul Gustav Kluetz, MD, a medical oncologist at the FDA’s Office of Hematology and Oncology Products.
Kluetz“We are now in a different era of drug development; patient voices are more important,” Kluetz said. “Thoughtful incorporation of patients into clinical trials and drug development is becoming a priority.”
Improved assessment of tolerability represents a real “PRO measurement opportunity,” Kluetz said. “Symptomatic adverse events are best assessed by patients themselves.”
Drug developers and regulators have long “looked at drug safety through the clinician’s lens,” Kluetz said. The emphasis is on precisely-measured lab test results and radiographic or histological variables.
PROs provide new insights
Such measures have proven to be very valuable to researchers and clinicians alike. But adding PROs to the mix can afford new insights into how treatments really affect patients.
PROs offer “different but complementary data to current clinician-reported safety data,” Kluetz explained. The US National Cancer Institute (NCI) has developed a PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™)-a “promising tool for this purpose,” Dr. Kluetz said.
PRO-CTCAE data can be collected using web portals between visits in just minutes, noted Basch.
Expanding adverse-events detection to include PROs is increasingly important as the durations of cancer treatments grow, and the field of drug development transitions from an era of cytotoxic chemotherapies infused intravenously at cancer centers, to more diverse treatments that are self-administered orally every day, he said.
“Progress in cancer treatment-and especially precision medicine approaches-begs for precision in adverse-events reporting,” agreed Diana T. Chingos, MS, MFA, a patient advocate and breast cancer survivor.
Kluetz pointed to dose-finding for anticancer tyrosine kinase inhibitors (TKIs) as one example of how PROs can help inform clinical practice.
“TKIs are commonly dose-modified due to toxicities,” he said, noting that dose interruptions and delays affect more than half of patients on commonly-prescribed TKIs. “For lenvatinib, dose interruption or delay affect 90% of patients.”
Combinations of TKIs and other agents with diverse mechanisms of action in anticancer treatment, including cytotoxic treatments, immunotherapies, cancer gene-targeting antibodies and small-molecule therapeutics, can lead to complex drug interactions and “low-grade but bothersome symptomatic toxicities” that impact patients.
Drug efficacy and PROs
There are currently significant challenges in assessing cancer drug efficacy using PRO measures, Kluetz cautioned.
“Many patients enrolled on cancer trials are asymptomatic with good performance status,” he explained-making it difficult to detect potential impacts on patients in real-world clinical settings.
But enrolling more symptomatic patients could allow researchers to use PROs to better measure symptom improvement and palliation.
Incorporating PROs into research will help develop treatments with an eye toward patients’ expressed needs and priorities.
Bringing PROs into clinical practice can also help practices and hospitals to bolster quality of care. ASCO has a PRO committee that has begun to test PRO quality-of-care measures. The development of so-called “ePRO” apps will allow patients to routinely self-report symptoms from home. Efforts are under way to integrate ePRO approaches with electronic health record (EHR) portals to allow the addition of longitudinal PRO data to patients’ medical records.