Abstract 1845P
Background
Drug development in oncology is changing rapidly. We described the methodological features of clinical trials supporting the registration of anti-tumour drugs in Europe.
Methods
We included all the drugs that received marketing authorisation for solid tumours by European Medicines Agency (EMA) between 2015-2020. We extracted data from European Public Assessments Reports, including setting, primary endpoint and quality of life (QoL).
Results
In the explored period, EMA issued 129 new indications (80 indications’ extensions). Half of them regarded non-small-cell lung cancer (NSCLC), breast cancer and melanoma (Table). Overall, most of the indications were for the advanced setting (91.5%) and front line therapy (62%). More than half were issued for immune checkpoint inhibitors (ICIs) and signal transduction inhibitors. Interestingly, 3 approvals were based on phase 1 trials and OS represented the primary endpoint only in 40.3% of indications, almost limited (77.5%) to ICIs’ trials. Surrogate endpoints [Progression Free Survival (PFS), other Time to Event and Objective Response Rate (ORR)] represented the leading endpoints for the approval in 58.2% of indications. QoL was never considered as primary endpoint but was evaluated in 106 cases (82.2%). We found that average Hazard Ratio for OS and PFS were 0.7 (SD 0.105) and 0.57 (SD 0.164), respectively. Table: 1845P
| Setting | Localized | 11 | 8.5% |
| Advanced | 118 | 91.5% | |
| Class of drugs | ICIs | 40 | 31% |
| Signal transduction inhibitors | 39 | 30.2% | |
| Angiogenesis inhibitors | 16 | 12.5% | |
| Cell cycle and DNA repair | 18 | 14% | |
| Chemotherapeutic agents | 8 | 6% | |
| Hormonal therapy | 7 | 5.5% | |
| Radiometabolic agent | 1 | 0.8% | |
| Disease | NSCLC | 32 | 25% |
| Breast Cancer | 20 | 15.5% | |
| Melanoma | 13 | 10% | |
| Ovarian Cancer | 10 | 8% | |
| Other | 54 | 41.5% | |
| Phase | 1 | 3 | 2.4% |
| 2 | 29 | 22.4% | |
| 3 | 97 | 75.2% | |
| Primary Endpoint | OS | 52 | 40.3% |
| PFS | 41 | 31.8% | |
| Other Time to Event | 9 | 7% | |
| ORR | 25 | 19.4% | |
| PK | 2 | 1.5% |
Conclusions
In this analysis, we intended to offer a picture of the recent drug development in oncology where most of the efforts led to broadening indications of pre-existing molecules and 25% of the drugs being approved without phase 3. Moreover, hard outcomes such as OS and QoL were under considered in pivotal trials and most of the indications were based on surrogate outcomes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Duranti: Financial Interests, Personal, Full or part-time Employment, Employment at AbbVie Medical Affair Division from July 2017 to March 2020: AbbVie. A. Pietragalla: Financial Interests, Personal, Full or part-time Employment, Employed at AstraZeneca Medical Affair Division from March 2015 to December 2018: AstraZeneca; Financial Interests, Personal, Training: GSK. D. Lorusso: Other, Personal, Other: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Other, Personal, Other: Pharmamar; Financial Interests, Institutional, Other, ENGOT trial with institutional support for coordination: Clovis; Financial Interests, Institutional, Other, ENGOT trial with institutional support for coordination: Genmab; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Funding: MSD; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Clovis; Non-Financial Interests, Principal Investigator: Genmab; Non-Financial Interests, Principal Investigator: GSK; Non-Financial Interests, Principal Investigator: Immunogen; Non-Financial Interests, Principal Investigator: Incyte; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Member of the Board of Directors: GCIG; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Clovis. A. Fabi: Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Lilly; Financial Interests, Advisory Role: Eisai; Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Celgene; Financial Interests, Invited Speaker: Eisai; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: MCI; Financial Interests, Invited Speaker: MSD; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker: Pfizer; Financial Interests, Invited Speaker: Roche. G. Scambia: Financial Interests, Research Grant: MSD; Financial Interests, Other: Tesaro; Financial Interests, Other: MSD; Financial Interests, Invited Speaker: Clovis; Financial Interests, Other: Clovis; Financial Interests, Other: Johnson & Johnson. G. Daniele: Financial Interests, Training: GSK. All other authors have declared no conflicts of interest.