OS Benefit Not Found For Majority Of Novel Oncology Indications After US FDA Approval

Almost two-thirds of novel oncology drug indications do not achieve an overall survival or patient-reported outcome benefit

medwireNews: A review of novel oncology treatments suggests that less than a third achieved an improvement in overall survival (OS) after approval by the US Food and Drug Administration (FDA). 

As reported in a letter to JAMA Oncology, 65 drugs were approved for 71 oncology indications between 2011 and 2017. 

But the majority (76%) of these indications were approved on the basis of a surrogate endpoint, such as response rate or progression-free survival, invasive disease-free survival, or a major cytogenetic or haematological response, and just 35% had OS or patient-reported outcome (PRO) data to support their submission for approval. 

Indeed, only 21% of the indications demonstrated an improvement in OS with their use before approval, report Chadi Nabhan, from Aptitude Health in Atlanta, Georgia, USA, and co-authors. 

And a median of 4.1 years after approval, OS improvement was only confirmed for a further eight indications, bringing the total up to 32% of the initial indications.  

Of concern, 18% of the indications failed to achieve an OS benefit and the impact of 49% of indications is yet unknown, the investigators say. 

Although PROs were included in 70% of the pivotal trials associated with initial approval of novel agents, just 14 of the indications demonstrated a statistically significant improvement in one or more PRO at the time of approval. Four drugs achieved a PRO benefit during post-approval follow-up, increasing the total proportion to 25%. 

“It is recognized that evaluation of OS can be challenging or unfeasible in some instances and is complicated by factors such as use of crossover trial design”, the investigators comment.

Nevertheless, the authors recommend: “Where possible, the requirement for postmarketing studies confirming an OS benefit, enforcement of timely completion of the studies, and action should those studies fail to show a benefit represents one avenue by which the FDA could improve the number of oncology drugs that provide true meaningful benefits to patients.” 



Zettler M, Basch E, Nabhan C. Surrogate end points and patient-reported outcomes for novel oncology drugs approved between 2011 and 2017 . JAMA Oncol; Advance online publication 3 July 2019. doi:10.1001/jamaoncol.2019.1760  

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