Triple-negative breast cancer

The EU has approved 15 indications of 8 drugs in triple-negative breast cancer. 8 of them need a biomarker result: BRCA1/2 (4), PD-L1 (3) and HER2 (1). 6 tumour-agnostic approvals also apply when the tumour carries the alteration.

Approved indications, Triple-negative breast cancer
Drug	Biomarker requirement	Regimen	Setting	Conditions

BRCA1/2 mutation4
Olaparib Lynparza	Germline BRCA1/2 mutation, HER2-negative	+ endocrine therapy	Adj. early	After neoadjuvant or adjuvant chemotherapy; High risk of recurrence
Olaparib Lynparza	Germline BRCA1/2 mutation, HER2-negative	Monotherapy	Adj. early	After neoadjuvant or adjuvant chemotherapy; High risk of recurrence
Olaparib Lynparza	Germline BRCA1/2 mutation, HER2-negative	Monotherapy	Any line advanced	After anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless not suitable; if HR-positive, progressed on or after prior endocrine therapy, or considered unsuitable for endocrine therapy
Talazoparib Talzenna	Germline BRCA1/2-mutations, HER2-negative	Monotherapy	Any line advanced	Previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless not suitable; prior endocrine-based therapy for HR-positive breast cancer unless considered unsuitable

HER2-low1
Trastuzumab deruxtecan Enhertuconditional	IHC 1+ or IHC 2+/ISH-negative, HER2-low	Monotherapy	2L advanced	After prior chemotherapy in the metastatic setting or disease recurrence during or within 6 months of completing adjuvant chemotherapy

PD-L13
Atezolizumab Tecentriq	IC ≥ 1%	+ nab-paclitaxel	1L advanced	No prior chemotherapy for metastatic disease
Pembrolizumab Keytruda	CPS ≥ 10	+ chemotherapy	1L advanced	No prior chemotherapy for metastatic disease
Sacituzumab govitecan Trodelvy	CPS ≥ 10	+ pembrolizumab	1L advanced	No prior systemic therapy for metastatic disease

ER/PR/HER2 negative1
Datopotamab deruxtecan Datroway	Triple-negative (ER-negative, PR-negative, HER2-negative)	Monotherapy	1L advanced	Not candidates for PD-1/PD-L1 inhibitor therapy

No biomarker required6
Pembrolizumab Keytruda	None	+ chemotherapy	Neoadj.	Then adjuvant monotherapy after surgery; Locally advanced or early-stage; high risk of recurrence
Pembrolizumab Keytruda	None	Monotherapy	Adj.	After neoadjuvant pembrolizumab + chemotherapy and surgical resection; Locally advanced or early-stage; high risk of recurrence
Bevacizumab Avastin	None	+ capecitabine	1L metastatic	Treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate; excluded if taxane and anthracycline-containing regimens received in the adjuvant setting within the last 12 months
Bevacizumab Avastin	None	+ paclitaxel	1L metastatic	None
Sacituzumab govitecan Trodelvy	None	Monotherapy	1L advanced	No prior systemic therapy for metastatic disease; Not candidates for PD-1 or PD-L1 inhibitor therapy
Sacituzumab govitecan Trodelvy	None	Monotherapy	2L advanced	After two or more prior systemic therapies, including at least one of them for advanced disease

Tumour-agnostic approvals6

Approved for any solid tumour that carries the alteration, wherever the tumour started.

Drug	Biomarker requirement	Regimen	Setting	Conditions

EpCAM1
Catumaxomab Korjuny		Monotherapy	2L	Malignant ascites; not eligible for further systemic anticancer therapy

HER21
Trastuzumab deruxtecan Enhertuconditional	HER2-positive (IHC 3+)	Monotherapy	2L advanced	After prior treatment; No satisfactory treatment options

NTRK fusion3
Entrectinib Rozlytrekconditional		Monotherapy	Any line	No prior NTRK inhibitor; Older than 1 month; disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options
Larotrectinib Vitrakviconditional		Monotherapy	Any line	Locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options
Repotrectinib Augtyroconditional		Monotherapy	Any line advanced	Prior NTRK inhibitor, or no prior NTRK inhibitor and treatment options not targeting NTRK provide limited clinical benefit or have been exhausted; Aged 12 years and older

RET fusion1
Selpercatinib Retsevmo		Monotherapy	Any line advanced	Treatment options not targeting RET provide limited clinical benefit, or have been exhausted; Aged 2 years and older

Biomarkers in triple-negative breast cancer

Label wording15

The sentence from section 4.1 of the SmPC that each indication above comes from.

Pembrolizumab (Keytruda)
KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early-stage triple-negative breast cancer at high risk of recurrence (see section 5.1).
Pembrolizumab (Keytruda)
KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early-stage triple-negative breast cancer at high risk of recurrence (see section 5.1).
Pembrolizumab (Keytruda)
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer in adults whose tumours express PD-L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease (see section 5.1).
Trastuzumab deruxtecan (Enhertu)
• HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy (see section 4.2).
Bevacizumab (Avastin)
Bevacizumab in combination with paclitaxel is indicated for first-line treatment of adult patients with metastatic breast cancer. For further information as to human epidermal growth factor receptor 2 (HER2) status, please refer to section 5.1.
Bevacizumab (Avastin)
Bevacizumab in combination with capecitabine is indicated for first-line treatment of adult patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline-containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Avastin in combination with capecitabine. For further information as to HER2 status, please refer to section 5.1.
Datopotamab deruxtecan (Datroway)
Datroway as monotherapy is indicated for the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy (see section 5.1).
Sacituzumab govitecan (Trodelvy)
in combination with pembrolizumab, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and whose tumours express PD-L1 with a combined positive score (CPS) ≥ 10 (see sections 4.2 and 5.1).
Sacituzumab govitecan (Trodelvy)
as monotherapy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and who are not candidates for PD-1 or PD-L1 inhibitor therapy (see section 5.1).
Sacituzumab govitecan (Trodelvy)
as monotherapy for the treatment of adult patients with unresectable or metastatic TNBC who have received two or more prior systemic therapies, including at least one of them for advanced disease (see section 5.1)
Olaparib (Lynparza)
monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy (see sections 4.2 and 5.1).
Olaparib (Lynparza)
monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy (see sections 4.2 and 5.1).
Olaparib (Lynparza)
monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2 negative locally advanced or metastatic breast cancer. Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments (see section 5.1). Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy.
Atezolizumab (Tecentriq)
Tecentriq in combination with nab-paclitaxel is indicated for the treatment of adult patients with unresectable locally advanced or metastatic TNBC whose tumours have PD-L1 expression ≥ 1% and who have not received prior chemotherapy for metastatic disease.
Talazoparib (Talzenna)
Talzenna is indicated as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2-negative locally advanced or metastatic breast cancer.