Abstract 753P
Background
Maintenance treatment with PARP inhibitors or bevacizumab is standard of care for front-line (FL) and platinum sensitive recurrent ovarian cancer (PSROC) following response to chemotherapy. Adverse events (AEs) on maintenance therapies are common and usually attributable to investigational treatments but could also be unrelated. Randomized controlled trials (RCTs) with blinded placebo design is the gold-standard for determining relative difference in efficacy and AEs between treatment arms. We performed a meta-analysis to quantify AE rates from the placebo arm of RCTs to determine AEs not due to active treatment agents.
Methods
We performed an electronic search to identify eligible RCTs in FL and PSROC settings. We extracted data from blinded placebo arms to estimate the risk of any AE, overall and specific grade 3 or greater (G≥3) AEs, and AE related treatment delay, dose reduction and discontinuation. We used the inverse variance method to pool data across RCTs.
Results
We identified 13 eligible RCTs (FL, N=8; PSROC, N=5) with 2223 patients who received placebo (FL, N=1540; PSROC, N=683). The majority experienced an AE of any grade (FL, 93.0%; PSROC, 95.2%), with substantial proportions experiencing G≥3 AEs (FL, 14.6%; PSROC, 18.2%) (Table). In the FL setting AEs led to treatment delay in 14.4%, dose reduction in 4.1% and discontinuation in 2.6%. Findings were similar for PSROC: 8.4%, 5.5% and 2.1% respectively. Table: 753P
| Adverse Events | FL | PSROC | ||||
| Any | P % (95% CI) | 93.0 | (91.3 - 94.8) | 95.2 | (93.6 - 96.8) | |
| I | 7.6 | (7.1 - 8.2) | 18.6 | (17.2 - 20.0) | ||
| G≥3 | Any | P | 14.6 | (11.3 - 17.9) | 18.2 | (15.3 - 21.1) |
| I | 1.4 | (1.1 - 1.8) | 3.5 | (2.8 - 4.1) | ||
| Neutropenia | P | 1.6 | (0.7 - 2.4) | 1.8 | (0.7 - 2.8) | |
| I | 0.1 | (0.1 - 0.2) | 0.3 | (0.1 - 0.6) | ||
| Anaemia | P | 1.3 | (0.3 - 2.3) | 0.5 | (0.0 - 1.1) | |
| I | 0.1 | (0.0 - 0.2) | 0.1 | (0.0 - 0.2) | ||
| Thrombocytopenia | P | 0.6 | (0.1 - 1.1) | 0.5 | (0.0 - 1.0) | |
| I | 0.06 | (0.0 - 0.1) | 0.1 | (0.0 - 0.2) | ||
| Abdominal Pain | P | 0.7 | (0.2 - 1.2) | 1.1 | (0.3 - 1.9) | |
| I | 0.1 | (0.0 - 0.1) | 0.2 | (0.1 - 0.4) | ||
| Nausea | P | 0.5 | (0.0 - 1.1) | 0.6 | (0.0 - 1.1) | |
| I | 0.04 | (0.0 - 0.1) | 0.1 | (0.0 - 0.2) | ||
| Vomiting | P | 0.6 | (0.0 - 1.4) | 0.7 | (0.1 - 1.4) | |
| I | 0.05 | (0.0 - 0.1) | 0.2 | (0.0 - 0.3) | ||
| Diarrhoea | P | 0.6 | (0.2 - 1.1) | 1.0 | (0.3 - 1.8) | |
| I | 0.06 | (0.0 - 0.1) | 0.2 | (0.0 - 0.3) |
P- percentage with adverse event I- incidence per month determined as adverse event rate by median progression-free survival.
.Conclusions
AEs experienced by patients on placebo are likely the consequence of previous treatment, patient factors, or disease. Current methods used to assess and report AEs in RCTs do not necessarily reflect AEs due to investigational treatments. Further studies are required to identify better approaches to report and analyse AEs likely associated with maintenance therapies in ovarian cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Friedlander: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: ACT genomics; Financial Interests, Institutional, Funding: BeiGene; Financial Interests, Institutional, Principal Investigator: BeiGene; Non-Financial Interests, Personal, Advisory Role: AbbVie. C.K. Lee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Norvatis; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen. All other authors have declared no conflicts of interest.