An analysis of the Value Framework of the American Society of Clinical Oncology (ASCO) shows that the Net Health Benefit score of cancer drugs continues to evolve over time after their FDA approval, based on data presented at the ASCO 2020 virtual annual meeting. This analysis showed a substantial change in more than 25% of cancer drugs in their Net Health Benefit 3 years after their initial approval.
“We often think about value as being static, but with more than a quarter of drug indications changing their initial classification, we should begin to think about value as a dynamic process that changes over time,” said Kelvin Kar-Wing Chan, MD, PhD, Medical Oncologist, Odette Cancer Centre, Toronto, Canada, at the meeting. “Keeping pace with that changing dynamic is important.”
Overall, 27.8% of the drugs had a change from their initial classification in clinical trials.
Regulatory approval of cancer drugs is often based on data presented in the primary publication of their clinical trials. Although these data give significant richness, said Dr Chan, the evidence evolves over time, and clinically relevant data, such as long-term overall survival and quality of life, are frequently reported in subsequent publications.
“The FDA wants to bring drugs to market, but the initial regulatory decision is often based on incomplete data,” he said. “Nevertheless, it’s usually a one-time decision. It’s rare that regulators revisit approvals unless there is an important safety concern.”
Dr Chan and colleagues evaluated all oncology indications for drugs approved by the FDA between 2006 and 2016 and identified the clinical trials that were scorable using the ASCO Value Framework version 2. They identified subsequent publications of relevant clinical trials with a follow-up of 3 years from the drug’s approval to evaluate changes in classification of the drug’s benefit using ASCO-defined threshold scores of ≤40 for low benefit and ≥45 for substantial benefit.
Mature Data Can Show Stronger or Weaker Benefit
The study included 54 FDA-approved indications and 89 subsequent publications. On average, no overall improvement was seen in the ASCO Net Health Benefit with longer follow-up and the evolution of evidence. However, in 27.8% of the clinical trials there was an overall change of benefit from the initial classification: based on the longer-term evidence, 11.1% of the drug indications became substantial, 9.3% became low, and 7.4% became intermediate.
“We initially hypothesized that we might find stronger signals of benefit over time with more mature data, but we really didn’t see that,” said Dr Chan. “The change in classification could be in either direction.”
Given these changes, reassessing the ASCO Net Health Benefit score when more evidence becomes available may be beneficial to inform clinical shared decision-making, said Dr Chan.
He noted that the other side of the equation is cost. A previous study by Dr Chan and colleagues using the ASCO Value Framework identified a clear trend of cancer drug prices at the time of launch in the past decade, without a corresponding increase in the clinical benefit.
“A lot of drug prices actually increase over time beyond inflation after postmarket launch,” he said. “Rightly or wrongly, the justification for an increase in price is often that the drug’s benefit will be greater with more mature evidence, but our data did not validate this justification.”
Based on these findings, the investigators emphasized that greater vigilance is needed to reassess the net benefits of the drug for a specific indication with more mature data.