Table 2.
Summary of phase II/III clinical trials investigating immunotherapy in BC with results from TIL analysis available.
| Trial (Design) | Setting, BC Subtype | Treatment Arms | TIL Variable (Cutoff a) | Outcomes | Results b |
|---|---|---|---|---|---|
| Keynote-086 [87] (II) e |
Advanced, TNBC | Pembrolizumab (2 cohorts) | Binary (median) | ORR DCR |
Combined cohort: OR for ORR = 1.26 (1.03–1.55), p = 0.01; OR for CDR 1.22 (1.02–1.46), p = 0.01 |
| Impassion-130 [86] (III) | Advanced, TNBC | NabP–Atezo NabP–Pbo |
Binary (10%) | PFS OS |
Predictive for Atezo benefit only in PD-L1+: PD-L1+/strTILs low→ PFS: HR 0.74 (0.54–1.03), p = 0.07, OS: HR 0.65 (0.41–1.02) p = 0.06. PD-L1+/strTILs high → PFS: HR 0.53 (0.38–0.74), p < 0.005; OS: HR 0.57 (0.35–0.92), p = 0.02. PD-L1-/strTILs high → PFS: HR 0.99 (0.62–1.57), p = 0.97; OS: HR 1.53 (0.76–3.08), p = 0.24 |
| Keynote-119 (III) [89] | Advanced, TNBC | Pembro CT PFC c |
Continuous, Binary (5%) |
BOR DCR PFS OS |
Positive association with clinical outcomes only in Pembro arm (p < 0.05) TILs <5% → Pembro vs. CT: median OS 5.9 vs. 8.8 months, HR 1.50 (1.14–1.97) TILs ≥5% → Pembro vs. CT: median OS 12.5 vs. 11.3 months, HR 0.75 (0.59–0.96) |
| Panacea [11] (Ib-II) |
Advanced, HER2+ | Trastuzumab–Pembro | Continuous | OR DCR |
Positive association with ORR (p = 0.006) and DCR (p = 0.0006) |
| KATE-2 (II-R) [90,91] |
Advanced, HER2+ | TDM1–Atezo TDM1–Pbo |
Binary (5%) | PFS OS |
Borderline positive association with OS in the atezolizumab arm TILs < 5% → Atezo vs. Placebo: mPFS 5.5 (3.9-9.6) vs NE (4.0-NE), HR 0.62 (0.37-1.03). 1-year OS 84.2% vs. 100%, HR 1.43 (0.51–4.01) TILs ≥ 5% → Atezo vs. Placebo: mPFS 8.5 (6.2-NE) vs 5.3 (4.0-9.5). 1-year OS 90.8% vs. 83.5%, HR 0.55 (0.26–1.12) |
| GeparNuevo [80] (II R) |
Neoadjuvant, TNBC | Durva d→ Durva–NabP→ Durva–EC Pbo→ Pbo–NabP→ Pbo–EC |
Continuous Categorical (10%, and 60%) |
pCR | strTILs (continuous): positive association with pCR, no predictive for Durva benefit OR 1.23 (1.04–1.6), p = 0.019 in Durva arm; OR = 1.39 (1.12–1.74), p = 0.003 in Placebo arm. intTILs: increase between baseline and end of the window phase associated with Durva benefit. OR 9.36 (1.26–69.65) p = 0.029 |
| NeoTRIPaPDL1 [85] (III) |
Neoadjuvant, TNBC | Cb–NabP–Atezo Cb–NabP |
Binary (40%) | pCR | Positive association with pCR, no predictive role Atezo arm: strTILs ≥40% vs. <40% → pCR 71.43% vs. 28.07%, p = 0.001 CT arm: strTILs ≥40% vs. <40% → pCR 63.16% vs. 33.9%, p = 0.009 No interaction with treatment arm. |
| GIADA [92] (II) |
Neoadjuvant, Luminal-B e | EC→ Nivo–ET | Continuous | pCR | Positive association with pCR (p < 0.001) |
a When applicable; b 95% confidence intervals reported in parentheses; c single agent chemotherapy per physician’s choice: capecitabine, eribulin, gemcitabine, vinorelbine; d in a proportion of patients, durvalumab was administered as induction treatment in the window phase. e luminal-B = hormone receptor-positive/HER2-negative, Ki67 ≥ 20% and/or grade 3. Abbreviations: BC, breast cancer; TN, triple-negative; str/int-TILs, stromal/intratumoral tumor-infiltrating lymphocytes; ORR, overall response rate; DCR, disease control rate; OR, odds ratio; CI, confidence interval; R, randomized; HR, hazard ratio; pCR, pathologic complete response, BOR, best overall response; (m)PFS, (median) progression-free survival; OS, overall survival; DCR, disease control rate; CT, chemotherapy; NabP, nab-paclitaxel; Pbo, placebo; Pembro, pembrolizumab; Atezo, atezolizumab; Cb, carboplatin; Durva, durvalumab; EC, epirubicin–cyclophosphamide; Nivo, nivolumab; ET, endocrine therapy.