Table 1.

The main results from principal phase 2 and 3 trials in metastatic and early breast cancer.

Trial	Study design	Setting	Number of subjects	Drug	Primary endpoint	Main results	Additional information	FDA approval
IMpassion13016	Phase 3 randomized controlled	mTNBC first line	902	Arm A: Nab-Paclitaxel + Atezolizumab Arm B: Nab-Paclitaxel + placebo	PFS and OS in ITT and PD-L1 + (hierarchical)	PFS: 7.2 vs 5.5mo HR = 0.80 (0.69-0.92) OS: 21.0 vs 18.7mo HR = 0.87 (0.725-1.02) PD-L1+: OS 25.4 vs 19.7mo HR = 0.69 (0.54-0.88) PFS: 7.5 vs 5.3 mo HR = 0.63 (0.50-0.80)	Testing in PD-L1+ population was not planned initially	Withdrawn
KEYNOTE-35519,20	Phase 3 randomized controlled	mTNBC first line	847	Arm A: Nab-Paclitaxel/Paclitaxel/Gemcitabine-Carboplatin + pembrolizumab Arm B: Nab-Paclitaxel/Paclitaxel/Gemcitabine-Carboplatin + placebo	PFS and OS in PD-L1 CPS score ≥10, ≥1, and ITT (hierarchical)	PFS: 7.5 vs 5.6mo HR = 0.82 (0.69-0.97) CPS ≥10: PFS: 9.7 vs 5.6mo HR = 0.66 (0.50-0.88) OS: 23 vs 16.1mo HR = 0.73 (0.55-0.95) CPS ≥1: PFS: 7.6 vs 5.6mo HR = 0.75 (0.62–0.91)	p value boundary for OS in CPS ≥1 not met, no ITT testing	Yes
IMpassion13117	Phase 3 randomized controlled	mTNBC first line	651	Arm A: Paclitaxel + Atezolizumab Arm B: Paclitaxel + placebo	PFS in PD-L1+ and ITT (hierarchical)	ITT: PFS: 5.7 vs 5.6mo HR = 0.86 (0.70-1.05)a OS: 19.2 vs 22.8 mo HR = 1.12 (0.88–1.43) PD-L1+: PFS: 6.0 vs 5.7mo HR = 0.82 (0.60–1.12) OS: 22.1 vs 28.3 mo HR = 1.11 (0.76–1.64)	a PFS in ITT population was not formally tested	No
SAFIR02-BREAST IMMUNO93	Phase 2	Metastatic HER2-negative 1st Line	199	Arm A: durvalumab Arm B: chemotherapy	PFS	mPFS: 2.7 vs 4.6mo HR = 1.4 (1.00–1.96), p = 0.047 mOS: 21.7 vs 17.9mo HR = 0.84 (0.54–1.29) p = 0.423 TNBC PD-L1+ (32) mOS = 27.3 vs 12.1mo HR = 0.37 (0.12–1.13) p = 0.0678	Ten patients had therapeutic break	No
KEYNOTE-11913	Phase 3 randomized open-label	mTNBC >1st Line	1098	Arm A: Pembrolizumab Arm B: Physician’s chemotherapy choice	OS in ITT and PD-L1+	OS: 9.9 vs 10.8 mo HR = 0.97 (0.82–1.15) PFS: 2.1 vs 3.3 mo HR = 1.60 (1.33–1.92) CPS >10: OS: 12.7 vs 11.6mo HR = 0.78 (0.57–1.06) PFS: 2.1 vs 4.3 mo HR = 1.14 (0.82–1.59)		No
Topacio/KEYNOTE-16230	Phase 2 open-label	mTNBC <third line	55	Niraparib + Pembrolizumab	ORR	ORR in full analysis population: 18% (90% CI 10–29) RR in gBRCAmut: 47% (90% CI 24–70)	DCR in full analysis 42% (90% CI 31–54)	No
PANACEA26	Phase 1b/2 open-label	Metastatic HER2-positive >first line	52	Trastuzumab + Pembrolizumab	OR in PD-L1+	In PD-L1+: OR: 6/40 patients (90% CI 7–29) PFS: 2.7mo (90% CI 2.6–4.0)	OS: PD-L1+: NR (13.1-NR) vs PD-L1-: 7mo (90% CI 4·9–9·8)	No
KATE227	Phase 2 randomized, double-blind	Metastatic HER2-positive ≥first line	202	Arm A: T-DM1 + atezolizumab Arm B: T-DM1 + placebo	PFS in ITT	PFS: 8.2 vs 6.8 8mo HR = 0.82 (0.55–1.23) p = 0.33 In PD-L1 + : PFS: 8.5 vs 4.1mo HR+: HR: 1.08 (0.64–1.82) HR-: HR: 0.58 (0.31–1.10)	OS: HR = 0.74 (0.42–1.30)	No
ENHANCE 194	Phase 2 randomized open-label	Metastatic Luminal >third line	88	Arm A: Eribulin + Pembrolizumab Arm B: Eribulin	PFS	PFS: 4.1 vs 4.2mo HR = 0.80 (0.50–1.26) p = 0.33	Cross-over 14 patients	No
MEDIOLAa29	Phase 1b/2 open-label	Metastatic HER2-negative >first line	34	Olaparib + Durvalumab	DCR	DCR at week 12: 80% (90% CI: 64.3–90.9) DCR at week 28: 50% (90% CI 33.9–66.1)	ORR at week 12 63.3% (95% CI 48.9–80.1)	No
GELATO-trial95	Phase 2	Metastatic HER2-negative Lobular <third line	40	Carboplatin + Atezolizumab	PFS at 6mo	4/23 patients free of PD at week 24 ORR: 19% CBR at week 24: 29%	First analysis
KEYNOTE-52234	Phase 3 randomized controlled	Neoadjuvant Adjuvant TNBC	1774	Arm A: Carboplatin + Paclitaxel + 4xAC + pembrolizumab -> pembrolizumab in adjuvant Arm B: Carboplatin + Paclitaxel + 4xAC + placebo -> placebo in adjuvant	8y-EFS	pCR: 64.8 vs 51.2% p < 0.001 PD-L1+: pCR 68.9 vs 54.9% Events: 15.7 vs 23.8% HR = 0.63 (0.48–0.82)	Favorable trend in OS; Long-term FU awaited	Yes
GeparNUEVO38	Phase 2 randomized controlled	Neoadjuvant TNBC	174	Arm A: Durvalumab + nab-paclitaxel -> EC Arm B: Placebo + nab-paclitaxel -> EC	pCR	pCR: 53.4 vs 44.2% OR:1.45(0.80–2.63) 3y-iDFS 84.9 vs 76.9% HR = 0.54, (0.27–1.09), stratified log-rank p = 0.0559 3y-OS: 95.1 vs 83.1% HR = 0.26 (0.09–0.79) p = 0.0076 in PD-L1+: pCR 58 vs 50.7% p = 0.363	Higher pCR in high TILs and high TMB and WoO sTILs stratification for iDFS	No
NeoTRIPaPDL137	Phase 3 randomized open-label	Neoadjuvant TNBC	280	Arm A: Carboplatin + Nab-Paclitaxel + atezolizumab -> adjuvant AC/EC Arm B: Carboplatin + Nab-Paclitaxel -> adjuvant AC/EC	5y-EFS	pCR: 48.6 vs 44.4% OR: 1.18 (0.74–1.89), p = 0.48 PD-L1+: pCR 51.9 vs 48% OR: 2.08 (1.64–2.65)	EFS data not mature TILs unbalanced	No
IMpassion03135	Phase 3 randomized controlled	Neoadjuvant TNBC	455	Arm A: Nab-paclitaxel + 4xAC+atezolizumab Arm B: Nab-paclitaxel + 4xAC + placebo	pCR in ITT and PD-L1+	pCR: 57.6 vs 41.1% p = 0.0044 PD-L1+: pCR 68.8 vs 49.3% p = 0.021	EFS data not mature	No
GIADA41	Phase 2	Neoadjuvant Luminal B	43	EC-> Nivolumab+ triptorelin + exemestane	pCR	pCR: 16.3% (7.4–34.9)	Any PD-L1	No
I-SPY 240	Phase 2 randomized open-label	Neoadjuvant HER2-negative	181	Arm A: weekly paclitaxel followed by AC+ pembrolizumab Arm B: weekly paclitaxel followed by AC [other arms in I-SPY-program not mentioned here]	pCR	pCR rates: HER2-: 44 vs 17% HR+ and HER2-: 30 vs 13% TNBC: 60 vs 22%	Pembrolizumab was the first of 10 agents in the I-SPY program to graduate in the HR-positive/ERBB2-negative signature.	No

AC anthracycline-cyclophosphamide, CBR clinical benefit rate, CPS combined positive score, DCR disease control rate, EC epirubicin-cyclophosphomide, EFS event-free survival, FU follow-up, HR hazard ratio, HR− hormone-receptor negative, HR+ hormone-receptor-positive, ITT intention-to-treat, OR overall response, ORR objective response rate, OS overall survival, pCR pathological complete response, PD progressive disease, PD-L1 programmed death-ligand 1, PFS progression-free survival, TILs tumor-infiltrating lymphocytes, TMB tumor mutational burden, TNBC triple-negative breast cancer, WoO window-of-opportunity.

^aOnly breast cancer cohort.