Table 3.

List of Endpoints to Consider as Potential Valid Measures of Efficacy

Endpoint	Definition
(p)CR	(Pathologic) complete response: defined as the disappearance of all signs of cancer in response to treatment
EFS/DFS/RFS	Event-free survival/disease-free survival/relapse-free survival: defined as the time from cancer treatment end to the appearance of first signs or symptoms of that cancer, or the appearance of first complications that the treatment was intended to prevent/delay, or death from any cause EFS is normally used in the neoadjuvant setting and DFS is used in the adjuvant setting
iDFS/MFS	Invasive disease-free survival: defined as the time between randomization and first invasive disease recurrence; primarily used in studies of patients with breast cancer Metastasis-free survival: defined as the time from start of treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body; primarily for patients with prostate cancer
MRD	Minimal residual disease: defined as the small proportion of cancerous cells that may remain after treatment when the patient shows no signs or symptoms of the disease; primarily used in trials with patients with hematologic malignancies
ORR	Overall/objective response rate: defined as the proportion of patients with a confirmed response of complete or partial response (usually tumor size reduction)
PRO	Patient-reported outcome: can directly measure clinical benefit (severity of cancer symptoms) Evaluated using validated measures that are routinely incorporated into clinical trial design, such as EQ-5D or SF-36 Some endpoints include a QoL component, such as TWiST (time without symptoms of disease and toxicity of treatment) or QAPFS (quality-adjusted PFS) NB: capturing QoL endpoints and powering for them may not always be feasible in RCTs; a high follow-up rate is needed for questionnaires
PFS	Progression-free survival: defined as the time from randomization to the date of first disease progression or death Related measures include PFS2 (time from randomization to tumor progression on next-line treatment or death from any cause), TTD (time to treatment discontinuation) and TTNT (time to next treatment)

Notes: Based on the FDA’s table of important cancer approval endpoints⁷⁹ and the National Cancer Institute dictionary of cancer terms.⁸⁰.

Abbreviations: EQ-5D, 5-dimension EuroQol questionnaire; FDA, Food and Drug Administration (USA); PRO, patient-reported outcome; QoL, quality of life; RCT; randomized controlled trial; SF-36, 36-item short-form health survey.