Table 2.

Trials of ICIs for recurrent/metastatic breast cancer and tissue-agnostic indications

Trial name	Phase	Setting	Control and immunotherapy arms	Key outcome measures for FDA approval
Trials leading to FDA approvals
IMpassion130	III	Previously untreated TNBC	Control (n=451): Placebo+nab-paclitaxel Immunotherapy (n=451): Atezolizumab+nab-paclitaxel	PD-L1 IC+ PFS 7.5 vs 5 months HR 0.62 (95% CI 0.49 to 0.78; p<0.001) ITT PFS 7.2 vs 5.5 months HR 0.80 (95% CI 0.69 to 0.92; p=0.002)
KEYNOTE-355	III	Previously untreated TNBC	Control (n=281): Placebo+investigator’s choice: nab-paclitaxel, paclitaxel, or gemcitabine+ carboplatin Immunotherapy (n=566): Pembrolizumab+investigator’s choice: nab-paclitaxel, paclitaxel, or gemcitabine+ carboplatin	CPS≥10 PFS 9.7 vs 5.6 months HR 0.65 (95% CI 0.49 to 0.86; p=0.0012) CPS≥1 PFS 7.6 vs 5.6 months HR 0.74 (95% CI 0.61 to 0.90; p=0.0014)
Hypothesis-generating trials
KEYNOTE-119	III	TNBC that has progressed on prior therapy	Control (n=310): Investigator’s choice: capecitabine, eribulin, gemcitabine, or vinorelbine Immunotherapy (n=312): Pembrolizumab	CPS≥10 OS 12.7 vs 11.6 months HR 0.78 (95% CI 0.57 to 1.06; p=0.0574) CPS≥1 OS 10.7 vs 10.2 months HR 0.86 (95% CI 0.69 to 1.06; p=0.0728) ITT OS 9.9 vs 10.8 months HR 0.97 (95% CI 0.82 to 1.15)
IMpassion131	III	Previously untreated TNBC	Control (n=220): Placebo+paclitaxel Immunotherapy (n=431): Atezolizumab+paclitaxel	PD-L1 IC+ PFS 6 vs 5.7 months HR 0.82 (p=0.20) ITT OS 19.2 vs 22.8 months HR 1.11
KATE2	II	HER2+breast cancer with prior trastuzumab and taxane therapy	Control (n=69): Placebo+trastuzumab emtansine Immunotherapy (n=133): Atezolizumab+trastuzumab emtansine	ITT Median PFS 8.2 vs 6.8 months HR 0.82 (95% CI 0.55 to 1.23; p=0.33)
Trials leading to tissue-agnostic approvals
Pooled analysis:  KEYNOTE-016  KEYNOTE-164  KEYNOTE-012  KEYNOTE-028  KEYNOTE-158	Multi-cohort, single-arm	MSI-H or dMMR tumors that have progressed on prior therapy	Immunotherapy (n=149; five patients with breast cancer): Pembrolizumab	ORR 39.6% (95% CI 31.7% to 47.9%) CR rate 7% DOR 1.6+ to 22.7+months (78% lasting ≥6 months)
KEYNOTE-158	Multi-cohort, single-arm	TMB-H tumors (≥10 mut/Mb) that have progressed on prior therapy	Immunotherapy (n=102; 0 patients with breast cancer): Pembrolizumab	ORR 29% (95% CI 21% to 39%) CR rate 4% Median DOR not reached (57% lasting ≥12 months; 50% lasting ≥24 months)

CI, confidence interval; CPS, combined positive score; CR, complete response; dMMR, mismatch-repair deficient; DOR, duration of response; FDA, Food and Drug Administration; HR, hazard ratio; IC, immune cell; ITT, intent-to-treat; MSI-H, microsatellite instability high; ORR, overall response rate; OS, overall survival; PD-L1, programmed death ligand 1; PFS, progression-free survival; R/M, recurrent/metastatic; TMB-H, high tumor mutation burden; TNBC, triple-negative breast cancer.