Table 1.
Immunotherapy in early-stage TNBC.
| KEYNOTE 522 [4,6] | IMPASSION 031 [12] | I-SPY2 [20] | |
|---|---|---|---|
| Phase | III | III | II |
| No. of patients | 1174 | 333 | 114 |
| Study design | pembrolizumab/placebo 200 mg q3w × C8 + carboplatin AUC5 q3w or AUC1.5 q1w + paclitaxel 80 mg/m2 q1w × C4, followed by doxorubicin 60 mg/m2 q3w × C4 cycles or Epirubicin 90 mg/m2 q3w × C4 + cyclophosphamide 600 mg/m2 q3w × C4 followed by adjuvant pembrolizumab/placebo × C9. | atezolizumab/placebo 840 mg q2w + nab-paclitaxel 125 mg/m2 × C12, followed by ddAC × C4, followed by adjuvant atezolizumab 1200 mg q3w × C11 vs. capecitabine for non pCR or follow up. | Paclitaxel 80 mg/m2 q1w × C12 +/− pembrolizumab 200 mg q3w × C4, followed by AC q3w × C4. |
| Primary endpoint(s) | pCR, EFS | pCR in ITT and PDL-1 + | pCR in ITT |
| % pCR (ICI vs. placebo) |
65% vs. 51% p < 0.001 | pCR: 58% vs. 41% (ITT); 69% vs. 49% (PDL-1 +) p = 0.004 |
pCR: 60% vs. 22% |
| EFS/DFS/OS (ICI vs. placebo) |
5yEFS 81.3% vs. 72.3% | PDL1+: DFS (HR 0.57, 95% CI 0.23–1.43); OS (HR 0.71, 95% CI 0.26–1.91) | N/A. Not powered for statistical significance. |
| Outcome summary |
The addition of pembrolizumab to NAC reduced the risk for recurrence, progression, complications, or death by 37% (HR, 0.63; 95% CI, 0.49–0.81). | atezolizumab increased pCR rate by 17%. No statistical significance in long-term survival endpoints despite consistent results in the PD-L1-positive population, numerically favored the atezolizumab. | pembrolizumab increased pCR rates by 38%. |
| Immure Related Adverse Effects Grade > 3 | 82% vs. 79% | 23% vs. 16% | 9% vs. 7% |
Footnote: dd, dose-dense; AC, doxorubicin + cyclophosphamide; AUC, area under curve; DFS, disease-free survival; EFS, event-free survival; ITT, intention to treat; OS, overall survival; PFS, progression-free survival; pCR, pathological complete response; PDL1, programmed death-ligand 1; +, positive; TNBC, (early/metastatic) triple-negative breast cancer; W, week.