TABLE 6

Outcomes in mesothelioma studies with immune checkpoint inhibitors, according to PD-L1 status

StudyPhaseSettingTreatmentTotal ptsPD-L1 evaluated ptsPD-L1 IHC clonePD-L1 statusORR according to PD-L1 statusDCR/clinical benefit according to PD-L1 statusmPFS according to PD-L1 status (months)mOS according to PD-L1 status (months)
NCT02399371 [126]II2nd/3rd linePembrolizumab646222C3<1%287%p=0.021NA2.8p=0.0349.9p=0.50
1–49%2025%NA4.110
≥50%1443%NA4.912.5
Quispel-Janssen [130]II2nd/3rd lineNivolumab343328–8<1%2421%NA33%p=0.43NANANANA
≥1%944%55%NANA
MERIT [127]II2nd/3rd lineNivolumab343228–8<1%128%NANANA∼3HR 0.725 (0.316–1.668)
p=0.4490
∼12HR 0.542 (0.208–1.415)
p=0.2021
≥1%2040%∼8∼17
Dutch EAP [136]Restrospective analysis≥2nd lineNivolumab10733SP263 or 22C3<1%229%OR 1.31 (1.00–1.72)
p=0.05
36%NA∼3HR 0.52 (0.23–1.20)
p=0.12
∼6HR 0.67 (0.27–1.64)
p=0.39
≥1%1136%54%∼4.5∼6
JAVELIN
Solid Tumor [132]
Ib≥2nd lineAvelumab5343Dako 73–10<1%2110%p=1.0NANA1.6 (1.4–6.8)HR 0.68 (0.34–1.36)7.5 (3.8–21.0)HR 0.56 (0.26–1.23)
≥1%2214%5.3 (1.4–12.0)20.2 (6.1–NE)
<5%277%p=0.341.7 (1.4–8.3)HR 0.64 (0.30–1.34)10.2 (3.8–21.0)HR 0.62 (0.27–1.42)
≥ 5%1619%5.3 (1.4–17.8)20.2 (4.9–NE)
INITIATE [133]II≥2nd lineNivolumab+ipilimumab343422C3<1%1916%p=0.01832%p=0.0374HR 0.39 (0.17–0.94)∼10HR 0.16 (0.04–0.73)
≥1%1547%73%∼11NR
≥50%5NA80%NANA
IFCT-1501 MAPS2 [134, 135]II≥2nd lineNivolumab12599#28–8/SP-263<1%5812.1%p=0.00241.4%p=0.23NANANANA
≥1%4139%57.3%
Nivolumab+ipilimumab<25%9216.6%p=0.00743.5%p=0.047
≥25%771.4%85.7%
NIBIT-MESO-1 [129]II1st/2nd lineDurvalumab+tremelimumab4038SP263<1%1822%nonsignificant
p-values
50%nonsignificant
p-values
5.2 (4.5–5.8)nonsignificant
p-values
1-year OS rate42%nonsignificant
p-values
≥1%2035%75%11.7 (6.9–16.5)66%
≥5%1735%71%8.5 (7.7–9.1)59%
≥10%1127%73%8.5 (7.5–9.4)55%
≥25%743%86%8.5 (8.2–8.7)62%
≥50%425%75%11.7 (8.9–14.5)66%
PROMISE-meso [104]III2nd linePembrolizumab7367SP263<1%36NANANANA3.7 (2.1–4.2)See the text for HR between treatment arms9.2 (6.0–19.2)See the text for HR between treatment arms
≥1%314.1 (1.9–4.3)13.8 (7.5-NE)
Gemcitabline/ vinorelbine7162<1%303.4 (2.0–4.3)9.5 (5.6–13.8)
≥1%322.5 (2.1–6.4)15.3 (6.4-NE)
DREAM [105]II1st lineDurvalumab+Cisplatin+Pemetrexed5451SP263<1%24NANANANA6.3 (5.3–10.4)Non apparent differencesNANA
≥1%276.6 (5.5–9.0)
PrE0505 [106]II1st lineDurvalumab+Cisplatin+Pemetrexed5541E1L3N<1%19NANANANANANA19.6p=0.97
1–49%1020.8
≥50%1218.7
CheckMate 743 [7]III1st lineNivolumab+ipilimumab30328928–8<1%58NANANANANANA17.3 (10.1–24.3)See the text for HR between treatment arms
≥1%23118 (16.8–21.5)
Platinum salt+pemetrexed302297<1%7716.5 (13.4–20.5)
≥1%22013.3 (11.6–15.4)

Pts: Patients; IHC: Immunohistochemistry; ORR: Objective response rate; DCR: Disease-control rate; mPFS: Median progression-free survival; mOS: Median overall survival; NA: Not available; HR: Hazard ratio; NE: Not estimable; NR: Not reached. #: Results are reported with regard to PD-L1 evaluation with 28.8 clone. Data between parenthesis indicate 95% confidence intervals.