1585MO - Factors associated with change in overall survival and quality of life between time of approval and post-marketing among anti-cancer therapies

Background

The US Food and Drug Administration (FDA) criteria for registration allow cancer drugs to be approved based on surrogate outcomes. Here, we explore factors associated with overall survival (OS) and quality of life (QoL) benefit both at the time of initial approval and in the post-marketing period (PMP).

Methods

For trials supporting FDA cancer drug approvals between January 2006 and December 2015, we performed a systematic search of Pubmed and ClinicalTrials.gov to identify updated OS and/or QoL data, with follow-up through to April 2019. We explored variables associated with improvement in OS or QoL in the palliative setting using logistic regression.

Results

Among 96 trials, approval was based on improved OS in 41%. Among 59 trials providing updated efficacy data in the PMP, 47% showed improved OS; 39% for the first time. Improved OS at any time was observed in 52% of all trials. Only 47% of trials reported patient-reported outcomes (PRO) initially. Of these, 58% demonstrated a significant improvement in at least one PRO. Among 50% of trials which reported updated PRO data, improved QoL was observed in 46%; 50% for the first time. Improved QoL was observed in 38% of all trials. There were statistically significant associations between improved OS at initial approval and regular approval (OR 21.38; p=0.004), orphan drug designation (OR 0.39; p=0.04), sample size (OR 1.70; p<0.001), most prevalent tumors (OR 2.40; p=0.041), and crossover (OR 0.16; p=0.001). There was a non-significant association between improved QoL at initial approval and open-label studies (OR 3.85; p=0.053). Improved OS in the PMP was associated with immunotherapy (OR 8.20; p=0.026) and drugs with companion diagnostics (OR 11.67; p=0.006). Improved QoL in PMP was associated with sample size (OR 0.73; p=0.031), immunotherapy (OR 9.14; p=0.02) and open-label studies (OR 8.89; p=0.048).

Conclusions

Factors associated with OS and QoL benefit differs at the time of approval and in the PMP. Initially, drugs for prevalent tumors with regular approval are associated with OS benefit. In the PMP, immunotherapy and drugs with companion diagnostic tests are associated with improved OS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J.C. Tapia: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Grünenthal Group. A. Barnadas: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Genomic Health International. E. Amir: Speaker Bureau/Expert testimony: Genentech/Roche; Honoraria (self): Apobiologix; Honoraria (self): Agendia; Honoraria (self): Myriad Genetics; Honoraria (self): Sandoz. A. Tibau: Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Genentech/Roche; Travel/Accommodation/Expenses: Ipsen; Honoraria (self): Eisai. All other authors have declared no conflicts of interest.