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.