|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Almost one-third of oncology drugs approved by the US Food and Drug Administration (FDA) over the course of nearly a decade had no updated data available to examine when researchers attempted to assess the change in the “substantial clinical benefit” following market authorization.
The researchers, who presented their findings during the ASCO20 Virtual Scientific Program, focused specifically on data from cancer drug trials that supported either their accelerated approval or regular approval from the FDA between 2006 and 2015.
The analysis included 102 trials that supported the approval of 59 drugs for 96 solid tumor indications. Of the 96 approved indications, 74 were regular approvals and 22 were accelerated approvals.
The researchers assessed the changes in each drug’s magnitude of clinical benefit at both the time of approval and at later phases (when the most recent data were available for that medication) using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Follow-up data for drugs that gained approval through the normal regulatory pathway were considered up until April 2019. For drugs that got accelerated approval, the investigators looked at data from initial and confirmatory trials. In addition, the investigators collected information on overall survival (OS) and patient quality of life (QoL) during 2 crucial time points in each drug’s life cycle.
At initial approval, 38% of drugs showed improved OS and 17% were found to improve QoL. Substantial clinical benefit was seen in 20% of initial approval trials according to the ESMO-MCBS and in 24% of trials using the ASCO-VF.
In the postmarketing period, scores for substantial clinical benefit generally improved regardless of the assessment model used: At follow-up, high clinical benefit was seen in 53% of trials according to the ESMO-MCBS and 50% of trials according to the ASCO-VF.
Nearly one-third of cancer drug trials (30%) have not reported updated data following FDA marketing approval. And although the majority of drugs that initially received accelerated approval between 2006 and 2015 were converted to regular approval during the postmarketing period, 4% of the drugs that traveled through this expedited regulatory pathway still do not have any postmarketing data available for review, according to researchers.
On multivariable and univariable analyses, single-arm trials (odds ratio [OR], 9.21; 95% CI, 1.36-62.29; P =.023), drugs with companion diagnostics (OR, 4.95; 95% CI, 1.01-24.22; P =.049), and drugs indicated for second- or later-line therapy (OR 7.80, 95% CI, 1.35-45.02; P =.022), were associated with improved ASCO-VF scores compared with the benefit scores at initial approval.
Meanwhile, immunotherapeutics (OR, 6.42; 95% CI, 1.27-32.60; P =.025) and drugs with companion diagnostics (OR, 6.86, 95% CI, 1.58-18.10; P =.004) were associated with better ESMO-MCBS scores at follow-up.
The investigators concluded that from initial approval to postmarketing phases, anticancer medications with companion diagnostic tests, immunotherapies, and drugs approved based on single-arm trials were associated with improved clinical benefit.
Study author Aida Bujosa, oncology resident at the Hospital de la Santa Creu i Sant Pau in Spain, told Cancer Therapy Advisor in an email that in the past few years (post-2015, or following when the study period concluded), the FDA has been more flexible in its mechanisms of approval, so some cancer drugs have been approved based on intermediate outcomes, such as progression-free survival, overall response rates, or were based only on single-arm trials.
She explained that some of these drugs — specifically immunotherapies or drugs that were approved based on a companion diagnostic tests — usually require more time compared with classic chemotherapy to prove differences in overall survival, or require confirmatory randomized controlled trials to demonstrate a true benefit. “The use of surrogate measures to support approval may be acceptable only if confirmatory trials are mandated in the postmarketing setting,” she added.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
Rodríguez AB, Molto C, Hwang TJ et al. Factors associated with change in the magnitude of clinical benefit of anti-cancer drugs in the post-marketing period. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 7052.