1713P - Non-inferiority oncology clinical trials in major journals: Purposes, methods and results

Background

Non-inferiority (N-I) trials in oncology aim to prove that an experimental intervention is not significantly worse than a reference treatment, while offering other advantages. Clear explanation of the trial design and chosen margins is crucial.

Methods

We searched in leading oncology and general medical journals (Annals of Oncology, Journal of Clinical Oncology, JAMA, JAMA Oncology, Lancet, Lancet Oncology and New England Journal of Medicine) for N-I randomized clinical trials on solid tumours. We included phase II/III trials published in the last five years (since April/2018) and analyzed the primary N-I endpoint, margin of N-I, reasons for the margin, results and funding.

Results

The search yielded 637 articles, 367 were excluded after title/abstract screening, 190 after full-text screening, resulting in 80 analyzed articles (44 on cancer drugs, 19 radiotherapy, 11 surgery, 5 diagnostics, 1 follow-up). N-I design reasons: less intense drug treatment (22), less intense or hypofractionated radiotherapy (n17), less aggressive or no surgery (16) and less toxic/more convenient drug schedules (16). The primary sites were breast cancer (28), head/neck and gastric cancers (9 each) and colon (7). Main scenarios: neo/adjuvant protocols (32) curative (20) and first-line (17). Most common primary endpoints: recurrence/disease free survival (25), progression free survival (21) and overall survival (17). 25 received support from for-profit organizations, mainly drug trials from pharmaceutical industries (18/25). Most primary outcomes were within the non-inferiority margin (60), however 27 (33%) did not explicitly state the reasons for choosing such margin. Median N-I margin for time-to-event outcomes was 1.27 (95% CI 1.2–1.32; hazard ratio), while for binary outcomes, it was 8% (95% CI 5.4%–10%). No significant differences were observed between the results (positive or negative) or the chosen margin according to funding or type of trial (drug or not).

Conclusions

Most oncology N-I clinical trials reported in major medical journals are about less intense, less toxic or more convenient drug schedules and are positive. A considerable part is funded by pharmaceutical industries and another sizable part lacks reporting the reasons for the chosen margin.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

R. B. Barreto.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.