Table 1.

List of surrogate endpoints in adult patients with breast cancer that may be considered and discussed with FDA for individual development programs of a drug or a biological product under both accelerated and traditional approval pathways.

Patient population	Disease status	Treatment setting	Surrogate endpoint	Type of approval	Drug mechanism of action
Patients with breast cancer	Early stage	Preoperative neoadjuvant therapy	pCR	Accelerated	Agnostic a
Patients with breast cancer and neuroblastoma	Early stage	Preoperative neoadjuvant therapy	EFS b	Accelerated/traditional c	Agnostic a
Patients receiving adjuvant therapy following complete surgical resection of colon cancer, colorectal cancer, melanoma, renal cell cancer, gastrointestinal stromal tumor, breast cancer, and adjuvant therapy for stage III non-small cell lung cancer	Early stage	Postoperative adjuvant therapy	DFS	Accelerated/traditional c	Agnostic a
Patients with breast cancer, ovarian cancer, renal cell carcinoma, pancreatic neuroendocrine cancer, colorectal cancer, head and neck cancer, non-small cell lung cancer, melanoma, tuberous sclerosis complex-associated subependymal giant cell astrocytoma and renal angiomyolipoma, Merkel cell carcinoma, unresectable or metastatic cutaneous basal cell carcinoma, urothelial carcinoma, cervical cancer, endometrial cancer, hepatocellular carcinoma, fallopian tube cancer, microsatellite instability-high cancer, gastric cancer, thyroid cancer, astrocytoma, Kaposi’s sarcoma, unresectable or metastatic cutaneous squamous cell carcinoma, NTRK gene fusion without a known acquired resistance mutation, prostate cancer, esophageal cancer, tumor mutational burden high solid tumors, cholangiocarcinoma, bladder cancer, and neuroblastoma	Unresectable locally advanced or metastatic stage	Therapy in metastatic setting	Durable objective ORR	Accelerated/traditional c	Agnostic a
Patients with breast cancer; renal cell carcinoma; pancreatic neuroendocrine tumor; soft tissue sarcoma; ovarian, fallopian tube, or primary peritoneal cancer; prostate cancer; thyroid cancer; colorectal cancer; non-small cell lung cancer; head and neck cancer; tuberous sclerosis complex; Merkel cell carcinoma; basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer; hepatocellular carcinoma; melanoma; astrocytoma; and gastrointestinal stromal tumors	Unresectable locally advanced or metastatic stage	Therapy for metastatic setting	PFS	Accelerated/traditional c	Agnostic a

Recreated from the FDA’s adult Surrogate Endpoint Table at https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure. BLA, Biologic License Application; DFS, disease-free survival; EFS, event-free survival; FDA, US Food and Drug Administration; NDA, New Drug Application; NTRK, neurotrophic tyrosine receptor kinase; ORR, overall response rate; pCR, pathological complete response; PFS, progression-free survival.

^aSince disparate mechanisms of action could be involved, mechanism agnostic refers to the absence of a causal pathway which is directly related to a surrogate endpoint.

^bDespite not yet used to support an approved NDA or BLA, this surrogate endpoint could be appropriate for use as a primary efficacy clinical trial endpoint for a drug or biologic approval.

^cEndpoints based on changes in tumor burden may be used for both traditional and accelerated approval depending on context of use, including factors such as disease, effect size, effect duration, residual uncertainty, and benefits of other available therapy.