Researchers from the University of California San Diego School of Medicine (CA, US) report that the utilization of individual genetics to develop personalized therapeutic approaches for cancer patients has resulted in improved response to treatment and longer periods of remission, even as early as Phase I clinical trials.
In a meta-analysis published recently in JAMA Oncology, the authors reviewed 346 Phase I clinical trials that involved 13,203 cancer patients. The team found that in precision medicine treatment arms, over 30% of patients responded to treatment as opposed to the 4.9 % that responded to treatment in the nonpersonalized arms. Patients that received personalized treatment also displayed improved progression-free survival, with a median of 5.7 months remission before their diseased worsened compared to 2.95 months for the others in the trials.
Lead author Maria Schwaederlé (UC San Diego Moores Cancer Center) commented: “Our analysis shows that in the era of precision medicine, Phase I clinical trials utilizing personalized therapy with a biomarker-based approach can do more than assessing the toxicity and side effects… These early trials can result in improved outcomes for patients, even among people whose disease is resistant to standard treatments, by selecting patients who will respond best using a personalized approach from the start.”
The study, which involved 58 precision medicine treatment arms and 293 nonpersonalized arms, also demonstrated that personalized medicine led to improved outcomes in different tumor types. Precision medicine was associated with improved treatment response rates in 24.5% of patients with solid tumors compared to a response of 4.5% in patients receiving nonpersonalized treatments; this was echoed in blood cancer patients, with 24.5% responding compared to 13.5% respectively. Across the tumor types, precision medicine led to longer progression-free survival, with 4.1 months compared to 2.8 months in solid tumors and 13.6 months compared to 4 months in blood cancers.
A series of subanalyses of 234 arms demonstrated first, that biomarker-assigned targeted therapies lead to improved response rates (31.1% response rates in personalized arms compared to 5.1% in other patients); and second, that therapies paired to biomarkers targeting genomic alterations performed better than biomarkers directed at protein overexpression, with a 42% response rate compared to 22.4% respectively.
“What we observed is that Phase I trials can serve both to inform us on the effectiveness of new therapies as well as identify patients likely to benefit most if a personalized approach is employed,” stated senior author Razelle Kurzrock (UC San Diego Moores Cancer Center). “Another important point is that targeted drugs in and of themselves are often quite useless if not combined with a patient’s individual tumor biomarkers to determine whether they are likely to benefit from a particular therapy,” Kurzrock concluded.