Predicting Real-World Effectiveness of Cancer Therapies Using Overall Survival and Progression-Free Survival from Clinical Trials: Empirical Evidence for the ASCO Value Framework

Abstract

Real-world OS treatment benefits were similar to those observed in RCTs based on OS endpoints, but were 16% less than RCT efficacy estimates based on surrogate endpoints. These results, however, varied by tumor and line of therapy.

Assessing the efficacy‐effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population‐based, real‐world data for contemporary parenteral cancer therapeutics

“…However, data describing whether the real‐world relative treatment effect for a novel therapy, as compared with a standard comparator arm, is similar in magnitude to the relative treatment effect from clinical trial data are limited. Evidence to support preserved real‐world effectiveness compared with a reference standard has been demonstrated in a review of the Surveillance, Epidemiology, and End Results and Medicare data for 18 cancer therapeutics used in breast, colorectal, lung, ovarian, and pancreatic malignancies . In a method similar to that used in the current analysis, Lakdwalla et al generated real‐world OS estimates for treatments and their corresponding RCT comparator using Surveillance, Epidemiology, and End Results–Medicare data.…”

“…In a method similar to that used in the current analysis, Lakdwalla et al generated real‐world OS estimates for treatments and their corresponding RCT comparator using Surveillance, Epidemiology, and End Results–Medicare data. As compared with the corresponding HR for OS in RCTs, the generated relative treatment effect through use of the novel treatment in the real world was largely preserved, with a calculated difference between the clinical trial and real‐world HR for OS of 0.6 (95% CI, ‐3.5% to 4.8%) . However, this positive concordance between relative estimates of treatment effect was limited to the inclusion of trial‐eligible patients only, thus highlighting how patient‐related factors are likely contributory to the observed efficacy‐effectiveness gap.…”

“…Evidence to support preserved real-world effectiveness compared with a reference standard has been demonstrated in a review of the Surveillance, Epidemiology, and End Results and Medicare data for 18 cancer therapeutics used in breast, colorectal, lung, ovarian, and pancreatic malignancies. 8 In a method similar to that used in the current analysis, Lakdwalla et al generated real-world Cancer April 15, 2020 OS estimates for treatments and their corresponding RCT comparator using Surveillance, Epidemiology, and End Results-Medicare data. As compared with the corresponding HR for OS in RCTs, the generated relative treatment effect through use of the novel treatment in the real world was largely preserved, with a calculated difference between the clinical trial and real-world HR for OS of 0.6 (95% CI, -3.5% to 4.8%).…”

“…An efficacy‐effectiveness gap is the difference in patient outcomes as observed in clinical trial data and real‐world evidence (RWE). It is becoming increasingly apparent that an efficacy‐effectiveness gap exists for systemic therapies in oncology . The etiology for this gap is believed to be multifactorial, with contributing factors including differences in patient populations, health care delivery, and variability in the experience of treating health care providers .…”

“…It is becoming increasingly apparent that an efficacy-effectiveness gap exists for systemic therapies in oncology. [6][7][8][9][10][11] The etiology for this gap is believed to be multifactorial, with contributing factors including differences in patient populations, health care delivery, and variability in the experience of treating health care providers. 12,13 Over time, Cancer April 15, 2020 clinical trials have become less representative of patients with cancer in real-world practice given that the inclusion criteria for participation has become increasingly more stringent.…”