Overview of recent advances in metastatic triple negative breast cancer

Table 1 Historical outcomes in metastatic triple negative breast cancer

	ORR (%)	PFS (mo)	OS (mo)
Single agent chemotherapy
1L	10.0-28.0	3.5-5.4	9.9-17.5
2L	6.0-18.0	2.7-3.4	9.2-15.2
Combination chemotherapy
1L	14.8-64.3	4.8-9.0	13.9-24.2
2L+	27.01-60.0	2.9-7.0	8.1-16.5

¹1-3Lines. Adapted from: Li et al[89]. ORR: Overall response rate; PFS: Progression free survival; OS: Overall survival.

Table 2 Immunotherapy as a monotherapy in metastatic triple negative breast cancer

Trial	n	Drug	ORR 1st line	ORR ≥ 1 prior line	Median OS (mo) 1st line	Median OS (mo) ≥ 1 line	Ref.
NCT01375842 Phase Ia	116	Atezolizumab	24%	6%	17.6	7.3	Emens et al[52], 2019
KEYNOTE-012 Phase Ib	32	Pembrolizumab		18.5		11.2	Nanda et al[50], 2016
JAVELIN/Phase Ib	58	Avelumab		5.2		9.2	Dirix et al[51], 2018
KEYNOTE-086 Phase II	170	Pembrolizumab	23.1%	5.3	18.0	9.0	Adams et al[53], 2019
KEYNOTE-119/Phase III	622	Pembrolizumab vs chemo		9.6 vs 10.6		CPS ≥ 1; 10.7 vs 10.2. CPS ≥10; 12.7 vs 11.6. CPS ≥ 20; 14.9 vs 12	Verret et al[83], 2019

ORR: Overall response rate; OS: Overall survival; CPS: Combined positive score.

Table 3 Early studies of Immunotherapy and chemotherapy in metastatic triple negative breast cancer

Trial	n	Drug	ORR 1st line	ORR ≥ 2 line	mOS 1st line	mOS 2nd line	Ref.
NCT01633970 Phase Ib	33	Atezolizumab + nab-paclitaxel	53.8%	30	24.2	12.4	Adams et al[55], 2019
KEYNOTE-150 Phase 1b/II	82	Pembrolizumab + Eribulin	25%	26.5	17.7	NE	Tolaney et al[57], 2018
Pilot and phase II. 1-2L1	29	Pembrolizumab + capecitabine or paclitaxel	43% pembro + cap. 23% pembro + paclitaxel		13.8 pembro + cap 7.9 pembro + pac		Page et al[90], 2019

¹One to two lines of prior treatment. Pembro: Pembrolizumab; Cap: Capecitabine; Pac: Paclitaxel; ORR: Overall response rate; OS: Overall survival.

Table 4 Phase III first line metastatic immunotherapy + chemotherapy

	IMpassion130 (PD-L1 inhibitor)	Keynote-355 (PD1 inhibitor)	IMpassion131 (PD-L1 inhibitor)
Drugs	Atezolizumab/nab-paclitaxel vs placebo/nab-paclitaxel	Pembrolizumab + chemotherapy (nab-paclitaxel or paclitaxel or gemcitabine/carboplatin vs placebo + chemo	Atezolizumab/paclitaxel vs placebo/paclitaxel
ITT (N)	451 vs 451 (1:1 randomisation)	566 vs 281 (2:1 randomisation)	430 vs 221 (2:1 randomisation)
Inclusion	≥ 1 yr DFI	≥ 6 mo DFI	≥ 1 yr DFI
PD-L1 status	IC [positive (≥ 1%) vs negative (< 1%)]	CPS [positive (≥ 1%) vs negative (< 1%)]	IC [positive (≥ 1%) vs negative (< 1%)]
	SP142 antibody ventana platform	PD-L1 IHC 22C3 pharmDx kit	SP142 antibody ventana platform
Primary endpoints	PFS and OS in ITT population	PFS and OS by PD-L1 status (CPS ≥ 10 and ≥ 1) in ITT	PFS and OS in PD-L1 positive cohort
Median FU	18.0 mo (ASCO 2019)	25.9 mo and 26.3 mo (ASCO 2020)	8.6 and 9 mo (ESMO 2020)
PFS in PD-L1 +	7.5 mo vs 5 mo	9.6 mo vs 5.6 mo	5.7 mo vs 5.6 mo
OS in PD-L1 +	25.4 mo vs 17.9 mo	Awaited	22.1 mo vs 28.3 mo

PD-1: Programmed death 1; PD-L1: Programmed death-ligand 1; ITT: Intention-to-treat; DFI: Disease Free Interval; IHC: Immunohistochemistry; OS: Overall survival; ASCO: American Society of Clinical Oncology; ESMO: European Society of Medical Oncology; PFS: Progression free survival; CPS: Combined positive score.

Table 5 Pivotal Phase III studies of poly adenosine diphosphate ribose polymerase inhibitors in patients with germline BRCA1/BRCA2 mutations

Trial	n	Drug	Median PFS (mo) 1st line	Media PFS (mo) ≥ 1 line	Media OS (mo) 1st line	Media OS (mo) ≥ 1 line	Ref.
OLYMPIAD	296	Olaparib		7.3		19.3	Robson et al[67], 2017
EMBRCA	431	Talazoparib		8.6		19.6	Litton et al[69], 2020
BROCADE3 (1st line)	337	Veliparib	14.5		33.5		Bardia et al[77], 2020

PFS: Progression free survival; OS: Overall survival.

Table 6 Key phase I/II/III involving antibody drug conjugates and targeted therapies

Trial	n	Drug	ORR 1st line	ORR ≥ 2 line	mPFS ≥ 2 line	mOS 1st line	mOS ≥ 2 line	Ref.
NCT01631552 phase II	108	Sacituzumab govitecan		33%	5.5		12.4	Schmid et al[61], 2020
NCT03310957 phase I/II	51	Pembrolizumab + ladiratuzumab vedoitin	54%		-			Han et al[78], 2020
NCT029380341 phase Ib/II	21	US-1402		33%	-			Kim et al[82], 2019
NCT03279257 phase 1b/II	40	Alpelisib		57%	7			Sharma et al[84], 2018
LOTUS phase II	124	Ipatasertib		40%	6.2			Kim et al[86], 2017
NCT02978716 phase II	102	Trilaciclib	43%			20.6/17.6		Tan et al[88], 2019
ASCENT phase III	529	Sacituzumab Govitecan		35%	5.6		12.1	Bardia et al[77], 2020

ORR: Overall response rate; PFS: Progression free survival; OS: Overall survival.