1586MO - Pivotal trial endpoints of drugs for rare and non-rare cancers in the US and Europe

Background

A key clinical outcome for new cancer drugs is improvement in overall survival (OS), defined as time from the date of randomization to the death from any cause. Surrogate endpoints, such as progression-free survival or overall response rate, can provide misleading information about efficacy. However, for rare cancers, as outlined by Rare Cancers Europe (RCE), a campaign developed by ESMO, surrogate endpoints may be of value or even the only way to show improvements timely. Furthermore, the FDA and EMA introduced orphan drug designation to encourage drug development for rare conditions. We categorized pivotal trial endpoints for approved cancer drugs by the FDA and EMA (OS vs. OS surrogates) and evaluated the correlation with orphan drug designations by the FDA and EMA as well as rare cancers as defined by the RCE.

Methods

We identified new cancer drugs FDA-approved between 2009 and 2019 that were indicated to treat solid and hematologic tumors in adults and that had also been approved by the EMA by December 2019. Fisher’s exact tests were conducted to assess the association between pivotal trial endpoints (OS vs. non-OS) and orphan drug designation by the FDA and EMA, as well as between pivotal trial endpoints and rare cancers as defined by RCE.

Results

76 drugs were approved by the FDA and EMA during the study period. In the US, 39 (51%) were approved based on OS by contrast to 49 (64%) in the EU; 50 (66%) drugs were designated orphan status by the FDA, 17 (22%) by the EMA. There was an association between rare cancers as defined by the RCE and drug indications designated with orphan status by the FDA (p=0.007) or EMA (p<0.001). However, there was no association between pivotal trial endpoints (OS vs. non-OS) and orphan drug designation by the FDA (p=0.094) or EMA (p>0.9). There was also no association between rare cancers as defined by the RCE and pivotal trial endpoints (p=0.2 [US] and p=0.3 [EU]).

Conclusions

Approval of drugs for non-rare cancers should be better aligned with OS as pivotal trial endpoint. Since surrogate measures may not be adequately predictive of patient-centred outcomes, cancer drugs approved based on surrogate endpoints should be closely followed up also after approval to offer patients optimal value.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

K.N. Vokinger.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.