1585P - Performance status restrictions in clinical trials leading to US food and drug administration (FDA) drug approval: A cross-sectional study of a decade (2014-2023)

Background

Performance status (PS) is one of the most frequently used eligibility criteria in cancer clinical trials (CTs). Patients (pts) with poorer PS are often excluded from enrolment, limiting the generalizability of trials’ efficacy and safety results to the real-world population.

Methods

In this cross-sectional study, we investigated the PS of pts enrolled in CTs which led to FDA drug approvals. We searched “FDA Drug Approvals and Databases” for announcements of new drugs for solid tumors published from 2014 to 2023. Subsequently, we identified the CTs leading to approvals and retrieved the corresponding publications and protocols. We assessed the study design and the Eastern Cooperative Oncology Group (ECOG) PS of enrolled pts of all included CTs and divided them into two consecutive time intervals: 2014-2018 and 2019-2023.

Results

We identified 260 CTs leading to FDA approvals: 179 (68.8%) and 81 (31.2%) included pts with ECOG PS 0-1 and 0-2, respectively. Overall, phase I and II CTs more frequently included pts with ECOG PS 2 than phase III CTs. In addition, the number of phase III CTs enrolling ECOG PS 2 pts decreased over time (Table). Baseline ECOG PS of enrolled pts was reported in 230 (88.5%) CTs’ publications. The median proportions (interquartile range) of enrolled pts with PS 0, PS 1, and PS 2 were 49.7% (IQR 37.3 – 64.9%), 44.9% (IQR 31.4 – 59.1%), and 3.3% (IQR 0.45 – 7.3%), respectively. Table: 1585P

Conclusions

Less than a third of CTs leading to FDA approvals between 2014 and 2023 allowed the enrolment of ECOG PS 2 pts and the median proportion of enrolled ECOG PS 2 pts was less than 4%. These findings highlight the need for strategies to increase the enrolment of pts with poor PS, especially in phase III CTs. Additional tools to better define the PS of pts during the pre-screening process and novel trial designs with pre-specified dedicated “poor PS cohorts” may reduce barriers to enrolment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G.M. Iannantuono: Financial Interests, Personal, Other, Honoraria/Consulting Fees: IQVIA. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Baxter Healthcare, GSK, Intuitive Surgical Inc., AstraZeneca&MSD, Olympus Europa, GSK, AstraZeneca&MSD, Olympus Europa; Financial Interests, Personal, Advisory Board, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Coordinating PI, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Coordinating PI, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Coordinating PI, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Coordinating PI, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Coordinating PI, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Coordinating PI, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. G. Daniele: Financial Interests, Personal, Invited Speaker: GSK, Gilead, Bayer; Financial Interests, Institutional, Research Grant: Gilead. All other authors have declared no conflicts of interest.