Table 4.

Results of PD-1/PD-L1 inhibition in advanced TNBC

Single-agent immunotherapyCombination with chemotherapy
Anti–PD-1Anti–PD-L1Anti–PD-1Anti–PD-L1
Pembrolizumab in PD-L1+ TNBC (KEYNOTE-012; ref. 111)Pembrolizumab in metastatic TNBC (KEYNOTE-086; refs. 112, 113)Atezolizumab in TNBC unselected for PD-L1 (108)Avelumab in TNBC unselected for PD-L1 (JAVELIN; ref. 116)Eribulin ± pembrolizumab in metastatic TNBC (ENHANCE-1/KEYNOTE-150; ref. 115)Atezolizumab + nab-paclitaxel in TNBC unselected for PD-L1 (114)Atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in metastatic TNBC (IMpassion130; ref. 117)
Tumor characteristics
Definition of PD-L1 positivity≥1% TC or any staining in stroma≥1% TC or any staining in stroma≥5% IC≥1% TC; ≥10% IC≥1% TC or any staining in stroma≥1% TC; ≥1% IC≥1% IC
PD-L1 status inclusion criteriaPositiveAll comersCohort A: pretreated, any PD-L1Cohort B: untreated, PD-L1+All comersAll comersAll comersStratum 1: No prior therapyStratum 2: 1–2 prior linesAll comersAll comers
Frequency of PD-L1 positivity among evaluable cases (%)65/111 (58.6)A: 105/169 (62.1)B: 128/207 (61.8)71/108 (65.7)TC: 33/48 (68.8)IC: 9/48 (18.8)49/98 (50)IC: 11/21 (52.4)369/902 (40.9)
Patient characteristics
Total number of patients enrolled32A: 170B: 8411558107 (S1: 66; S2: 41)32902
Total number of patients included in efficacy analysis27A: 170B: 84112b58107 (106b)32902
Median prior lines of therapy in metastatic setting (range)2 (0–9)A: NAB: 07 (0–21)NAcS1: 0S2: 1–25 (1–10)0
Efficacy
ORR, %18.5A: 4.7Overall: 9.85.2Overall: 26.4Overall: 37.5ITT: 56 vs. 45.9
B: 22.6First line: 26.3S1: 29.2First line: 46.1
Second line: 3.6S2: 22Second line: 22.2
Third/+ line: 7.7Third/+ line: 40
ORR in PD-L1+ cohort, %18.5A: 4.8B: 22.612.722.2d30.636.3d58.9 vs. 42.6
CBR, %25.9aA: 7.6NA31aOverall: 36.881.3aNA
B: 25S1: 40
S2: 31.7
Median PFS, mo.1.9 (1.7–5.5)A: 2.0 (1.9–2)NA1.5 (1.4–1.7)Overall: 4.2 (4.1–5.6)NEITT: 7.2 vs. 5.5; HR, 0.8 (0–69–0.92)
(95% CI)B: 2.1 (2.0–2.3)S1: 4.9 (4.1–6.1)PD-L1+: 7.5 vs. 5; HR, 0.62 (0.49–0.78)
S2: 4.1 (2.1–6.2)
Median OS, mo.11.2 (5.3–NR)A: 8.9 (7.2–11.2)9.3 (7.0–12.6)9.2 (4.3-NE)Overall: 17.7 (13.7–NE)NEITT: 21.3 vs. 17.6; HR, 0.84 (0.69–1.02)
(95% CI)[CR, PR, or SD: NR; PD: 7.1 (6.3–8.8)]B: 19.2 (11.3–NE)S1: 17.7 (13.3–NE)S2: 16.3 (12.4–19.2)(8–NE)PD-L1+: 25 vs. 15.5; HR, 0.62 (0.45–0.86)
  • NOTE: Response rates are per RECIST 1.1 criteria.

  • Abbreviations: TNBC, triple-negative breast cancer; TC, tumor cells; IC, immune cells; ORR, objective response rate; CBR, clinical benefit rate (defined as complete response, partial response, or stable disease for ≥24 weeks); mo., months; NR, not reached; NE, not estimable; NA, not available; PFS, progression-free survival; OS, overall survival; CI, confidence interval; ITT, intent-to-treat population; HR, hazard ratio.

  • aDCR is defined as confirmed complete, partial response, or stable disease as best response.

  • bNumber of patients considered objective response–evaluable.

  • cIn the overall population, the median number of prior lines of therapy in any setting was 4 (range, 1–10). In the TNBC cohort, 50% had received ≥2 prior lines of therapy for metastatic disease.

  • dAccording to PD-L1 positivity in IC.