Improved data on prognosis are vital for Acute Myeloid Leukemia (AML) patients since there are high relapse rates. These data are of great use to the treating physician and can be used to generate more treatment guidelines and improve patient outcomes.
Clinical trials are the main source of evidence for evaluating the safety and efficacy of new therapeutic advancements. Though, other than providing data on the efficacy of a new therapeutic agent, what other information on patient outcomes can be truly gleaned from these data that can be extrapolated into a real world setting?
Østgård L. S. et al. from Aarhus University Hospital, Denmark, carried out a population-based cohort study of newly diagnosed patients with AML in Denmark treated with intensive chemotherapy in-trial versus patients off-trial. They analyzed the Complete Remission Rates (CRR), accrual rates and Relative Risks (RR) of death at 90-days, 1-year and 3-years for both patient groups. The key results demonstrated that patients in the clinical trial setting had better survival and CRR (80.2% in-trial patients versus 68.6% in patients treated off-trial).
However, the inclusion criteria for patient selection for clinical trials are very distinct and narrow. For example, patients with poor performance status, elderly patients with co-morbidities and patients with secondary AML are often excluded from clinical trials.
Hence, the authors state that the validity of the data generated in the clinical trial setting relating to prognosis is questionable. Instead, the authors recommended further investigations employing real world studies in order to gain more robust data on prognosis. The study was published in Oncotarget in October 2016
Please see the published results from the abstract below
Clinical trials are critical to improve AML treatment. It remains, however, unclear if clinical trial participation per se affects prognosis and to what extent the patients selected for trials differ from those of patients receiving intensive therapy off-trial. We conducted a population-based cohort study of newly diagnosed Danish AML patients treated with intensive chemotherapy between 2000-2013. We estimated accrual rates and compared characteristics, complete remission (CR) rates, and relative risks (RRs) of death at 90-day, 1-year, and 3-years in clinical trial patients to patients treated off-trial. Of 867 patients, 58.3% (n = 504) were included in a clinical trial. Accrual rates were similar across age groups (p = 0.55). Patients with poor performance status, comorbidity, therapy-related and secondary AML were less likely to be enrolled in trials. CR rates were 80.2% in trial-patients versus 68.6% in patients treated off- trial. Also, trial-patients had superior survival at 1-year; 72%, vs. 54% (adjusted RR of death 1.28(CI = 1.06-1.54)), and at 3 years; 45% vs. 29% (adjusted RR 1.14(CI = 1.03-1.26)) compared to patients treated off-trial. Despite high accrual rates, patients enrolled in clinical trials had a favorable prognostic profile and a better survival than patients treated off-trial. In conclusion, all trial results should be extrapolated with caution and population-based studies of "real world patients" have a prominent role in examining the prognosis of AML.