Table 3.
Results of the exploratory studies of TILs in TNBC patients treated with PD-1/PD-L1 inhibitors.
| Application | Agents | Study | Combined Drug | N | Group | Results | Levels of TILs |
|---|---|---|---|---|---|---|---|
| Early TNBC | Pembro | KEYNOTE-173 (35) | Pembro + chemotherapya | 60b | •Available pre-treatment sTILs date of ypT0/Tis ypN0 | •pCR :60% vs 40% h | •Median (IQR): 42% (95% CI,10-74) vs 10% (95% CI,5-25) c $ |
| •Available on-treatment sTILs date of ypT0/Tis ypN0 | •pCR :57% vs 43% h | •Median (IQR): 65% (95% CI,5-89) vs 25% (95% CI,2-48) e $ | |||||
| •Available pre-treatment sTILs date of ypT0 /ypN0 | •pCR :58% vs 42% h | •Median (IQR): 40% (95% CI,10-75) vs 10% (95% CI,5-38) d $ | |||||
| •Available on-treatment sTILs date of ypT0 /ypN0 | •pCR :53% vs 47% h | •Median (IQR): 65% (95% CI,5-86) vs 25% (95% CI,3-60) f $ | |||||
| Advanced TNBC | Pembro | KEYNOTE-086 (27, 31, 32) | single-agent pembro |
•Cohort i
A: 147 B:46 |
•Cohort A | •ORR :6% vs 2%j | •Median (IQR): 10% (95% CI,7.5-25) vs 5% (95% CI,1-10) k $ |
| •Cohort B | •ORR :39% vs 9%j | •Median (IQR): 50% (95% CI,5-70) vs 15% (95% CI,5-37.5) k $ | |||||
| Advanced TNBC | Atezo | Impassion130 (24, 36, 37) | Atezo/ placebo + nab-paclitaxel | 902 | •Any PD-L1, sTILs<10% | •m PFS: 5.6 mo vs 5.4 mol
HR=0.86 (0.73-1.02) |
•sTILs<10%, any CD8 |
| •m OS: 19.2 mo vs 18.1 mol
HR=0.88 (0.72-1.08) |
|||||||
| •Any PD-L1, sTILs≥10% | •m PFS: 8.3 mo vs 6.1 mol
HR=0.64 (0.50-0.84) $ |
•sTILs≥10%, any CD8 | |||||
| •m OS: 25.0 mo vs 20.0 mol
HR=0.75 (0.54-1.03) |
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| PD-L1 ≥1%, sTILs<10% | •m PFS: 6.4 mo vs 4.7 mol
HR=0.80 (0.59-1.10) |
•sTILs<10%, any CD8 | |||||
| •m OS: 19.1 mo vs 17.6 mo •HR=0.74 (0.50-1.10) |
|||||||
| PD-L1 ≥1%, sTILs≥10% | •m PFS: 9.0 mo vs 5.4 mol
HR=0.54 (0.39-0.75) $ |
•sTILs≥10%, any CD8 | |||||
| •m OS: 30.0 mo vs 18.2 mol
•HR=0.54 (0.39-0.75) $ |
|||||||
| PD-L1 <1%, sTILs<10% | •m PFS: 5.6 mo vs 5.5 mol
HR=0.90 (0.73-1.10) |
•sTILs<10%, any CD8 | |||||
| •m OS: 19.3 mo vs 18.2 mol
HR=0.95 (0.75-1.20) |
|||||||
| PD-L1 <1%, sTILs≥10% | •m PFS: 7.2 mo vs 9.0 mol
HR=0.92 (0.59-1.44) |
•sTILs≥10%, any CD8 | |||||
| •m OS: 23.7 mo vs 24.5 mol
HR=1.04 (0.59-1.82) |
N, number of patients; TC, tumor cells; IC, immune Cells; IQR, interquartile range; $, indicates statistical significance; pCR, pathological complete response.
a: Pembro + taxane with or without carboplatin, and then doxorubicin and cyclophosphamide before surgery; b: 53 patients have pre-treatment sTILs data and 49 patients have on-treatment sTILs data; c: Median (IQR) TIL level in responders vs non-responders, P= 0.0059, AUROC (90% CI) 0.653 (0.527-0.779); d: Median (IQR) TIL level in responders vs non-responders, P= 0.0091, AUROC (90% CI) 0.638 (0.512-0.764); e: Median (IQR) TIL level in responders vs non-responders, P= 0.0085, AUROC (90% CI) 0.690 (0.564-0.817); f: Median (IQR) TIL level in responders vs non-responders, P= 0.0097, AUROC (90% CI) 0.676 (0.547-0.806); g: DCR (CR + PR + SD ≥ 24 weeks; h: Number of responders/number vs Number of no-responders/number, and patients not assessable for pCR were considered non-responders; i: 193 patients had evaluable tumor samples: 147 from cohort A, 46 from cohort B; j: ORR in patients with TIL level ≥vs<median; k: Median (IQR) TIL level in responders vs non-responders, and patients without response data were counted as non-responders. Response data included complete response or partial response; l: Atezo + nab-paclitaxel vs placebo + nab-paclitaxel.