Physicians' Perception of the Evidence in Relation to Primary Endpoints of Clinical Trials on Breast Cancer

Abstract

Objective: To investigate physicians' perception of the evidence of clinical trials on breast cancer.

Methods: A survey was conducted by the Chinese Society of Breast Surgeons. We investigated the physicians' perception of meaningful endpoints, appropriate follow-up duration, and clinically acceptable benefit through online questionnaires.

Results: Among 278 validated questionnaires, the majority of the questions had no consistent answer. For local treatment, 30.6, 28.8, and 28.4% of participants regarded locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) as the most meaningful endpoint, respectively, 47.5% believed that 5-year follow-up can alter clinical practice, and 34.5% thought it should be >10 years. In the adjuvant setting, 45.7, 38.5, and 12.9% regarded DFS, OS, and LRR as the most meaningful endpoint, respectively, 52.5% thought that 10-year follow-up was solid, while 37.4% thought that 5-year follow-up was enough. In the advanced setting, 49.6, 24.1, and 23.7% considered progression-free survival, quality of life, and OS the most meaningful endpoint, respectively, and 39.6 and 28.8% considered that a follow-up of 1 year and 3 years, respectively, was meaningful. Similarly, the clinically acceptable absolute difference was inconsistent.

Conclusion: Most Chinese oncologists advocated that surrogate endpoints could be used in certain circumstances, though OS was the most reliable one in breast cancer studies. Doctors' perceptions of follow-up time and magnitude of benefit vary widely, reflecting the fact that there are many unanswered questions about supporting the use of new cancer treatments; a common understanding needs to be reached, such as a very consensual surrogate endpoint and a meaningful sufficiently large therapeutic benefit.

Keywords: Breast cancer; Clinical trial; Primary endpoint.

Fig. 1

The most valuable endpoint in the investigation of local treatment (A), adjuvant systemic therapy (B), and systemic salvage treatment (C) for breast cancer. AE, adverse effect; BCSS, breast cancer-specific survival; DFS, disease-free survival; LR, local recurrence; LRR, locoregional recurrence; OS, overall survival; PFS, progression-free survival; QOL, quality of life.

Fig. 2

The meaningful follow-up time in trials investigating local recurrence (A), adjuvant systemic treatment (B), and systemic salvage treatment (C) of breast cancer.

Fig. 3

Meaningful absolute survival benefit when the primary endpoint is OS (A), DFS (B), LR (C), or PFS (D). DFS, disease-free survival; LR, local recurrence; OS, overall survival; PFS, progression-free survival.