Oncology Research Has Shifted Toward New Endpoints, but Further Analysis is Needed
Cancer trials have seen an evolution to more quickly deliver oncology therapies to patients, with researchers adopting the use of new endpoints in their trials, but further assessments of these endpoints are warranted due to conflicting opinions that persist among healthcare payers.
A number of oncology endpoints have been used traditionally for regulatory approval, including overall survival, progression-free survival and objective response rate, as well as one-year survival, five-year survival, complete response rate and duration of response. Those endpoints are well established with healthcare payers, who view them with confidence in making coverage decisions, according to a new IQVIA report.
But scientific progress has been made in recent years with the delivery of novel cancer drugs that have been able to reduce the size of tumors and delay their growth. That progress is linked to an increased use of surrogate endpoints to support traditional and accelerated oncology approvals alongside overall response rate/duration of response measurements. Regulators, too, have grown to accept the use of evolving endpoints and granted approvals based on them, with the FDA granting 194 unique cancer drug approvals for 132 drugs based on surrogate endpoints between 1992 and 2019, according to the new report.
The push to use surrogate endpoints, and their widespread adoption, has been fueled mainly by the large sample size and potential years of long-term follow-up necessitated by endpoints that measure survival. Additionally, survival can be potentially confounded or diminished by effective therapies taken post-progression, IQVIA said.
But for healthcare payers, questions remain about drugs approved by the FDA and other regulators based on those endpoints. IQVIA found that while the use of surrogate endpoints is ramping up in both the U.S. and EU for oncology therapies, their suboptimal predictive value of overall survival has given way to skepticism among payers in some countries.
Janssen’s Erleada (apalutamide), for example, was approved based on surrogate endpoints, but evaluations showed a limited amount of payer acceptance of those surrogate endpoints as appropriate measurements of mortality. Similarly, regulators also accepted the evaluation of disease control rate, an evolving endpoint, for AstraZeneca’s Tagrisso (osimertinib), but neither Germany’s G-BA nor France’s HAS cited the endpoint in their decision rationales, as AZ’s Tagrisso trial used overall survival and objective response rate for its primary endpoints, the company found.
And the UK’s National Institute for Health and Care Excellence (NICE) has made clear that it wants to see evidence supporting surrogate-to-final endpoint outcome relationships as well as details on how those relationships are quantified for use in modeling. Because of this wariness that persists, emerging endpoints should be persistently evaluated, IQVIA said.
In addition to continuous monitoring, IQVIA recommended that real-world evidence be used to “bridge the gap” between the evidentiary requirements of regulators, payers and prescribers and “better translate regulatory approval into reimbursement and patient access.”
To help with payer skepticism, IQVIA suggests the use of managed entry agreements (or innovative contracts) geared toward managing potential healthcare coverage with additional data, including real-world evidence, when concerns exist about the availability of long-term data at product launch.
According to IQVIA, surrogate endpoints have the most viability in situations where robust validation studies are reasonably likely to predict clinical benefit. These studies are limited to the specific tumor type, setting (adjuvant/metastatic), line of therapy, agent types (cytotoxic vs. targeted therapies) and specific surrogate-outcome pairings. As time goes on, the acceptance of surrogate endpoints in future market approvals will hinge significantly on their proper application and rationales for use, the company said.
Read the full report here: https://bit.ly/3AYTVus.