TABLE 4

Outcomes in small cell lung cancer (extensive stage) studies with immune checkpoint inhibitors, according to tumour mutational burden

Trial [ref.]IMpower 133 [4, 83]CheckMate 032 [92]CheckMate 032 [92]KEYNOTE-158 [90]Ricciuti et al. [99]
Study phaseIIII/III/IIIIRetrospective series
SettingFirst-line≥2nd line≥2nd line≥2nd line≥2nd line
TreatmentCarboplatin+etoposide ± atezolizumabNivolumabNivolumab+ipilimumabPembrolizumabPD-1 ± CTLA-4 ICIs
Total patients40324514610752
Evaluated patients346133787552
Methods
Material
Targeted NGS 394 genes BloodWES tumour and/or bloodWES tumour and/or bloodTargeted NGS 324 genes FoundationOne CDxTM assay (v3.3) TumourTargeted NGS 282 genes Tumour
Patient groupsMut/Mb cut-offMut tertilesMut tertilesMut/Mb cut-offMut/mb 50% percentiles
≥10≥16Low (0–142)Medium (143–247)High (≥248)Low (0–142)Medium (143–247)High (≥248)<10≥10Low (≤9.68)High (>9.68)
TMB2128042444727252641342626
ORRNA4.8%6.8%21.3%22.2%16%46.2%9.6%29.4%7.7%23.1%
p=0.25
DCRNANANANANANANANANA19.2%57.7%
p=0.01
mPFS (months)<10: HR 0.78
(0.54–1.12)
≥10: HR 0.69
(0.52–0.93)
<16: HR 0.73 (0.56–0.94)
≥16: HR 0.68
(0.43–1.10)
1.3 (1.2–1.4)1.3 (1.2–1.4)1.4 (1.3–2.7)1.5 (1.3–2.7)1.3 (1.2–2.1)7.8 (1.8–10.7)NANA1.2 (0.9–1.8)3.3 (1.9-NR)
HR 0.37 (0.20–0.69) p<0.01
1-year PFSNANA3.1%21.2%6.2%8%30%NANA7.7%29.9%
mOS (months)<10: HR 0.73
(0.49–1.08)
≥10: HR 0.73
(0.53–1.00)
<16: HR 0.79 (0.60–1.04)
≥16: HR 0.58 (0.34–0.99)
3.1 (2.4–6.8)3.9 (2.4–9.9)5.4 (2.8–8.0)3.4 (2.8–7.3)3.6 (1.8–7.7)22.0 (8.2-NR)NANA2.5 (1.6–6.8)10.4 (8.5-NR)
HR 0.38 (0.19–0.77) p<0.01
1-year OSNA22.1%26%35.2%23.4%19.6%62.4%NANA19%48.4%

Data between parenthesis indicate 95% confidence intervals. TMB: tumour mutational burden; ORR: objective response rate; DCR: Disease control rate; mPFS: Median progression-free survival; mOS: median overall survival; OS: overall survival; NGS: next-generation sequencing; Mut/Mb: mutations/megabase; NA: not available; HR: Hazard ratio; WES: Whole exome sequencing; ICIs: Immune checkpoint inhibitors; NR: not reached.