Table 3.

Univariate and multivariate analyses of survival from locally advanced or metastatic disease (excluding patients treated with immunotherapy; N = 1,415 patients).a

VariableGroupPatients, N (%)Median survival (weeks)HR OS (95% CI)Pa univariate
Age, y<60826 (58%)250Reference Group
≥60589 (42%)1701.57 (1.33–1.84)3.83 × 10−8
SexWomen716 (51%)189Reference Group
Men699 (49%)1721.07 (0.91–1.25)0.41
EthnicityAfrican-American53 (4%)2571.03 (0.67–1.60)5.1 × 10−3
Asian137 (10%)1701.31 (1.02–1.68)
Hispanic194 (14%)2130.95 (0.75–1.21)
Other60 (4%)921.80 (1.26–2.58)
NHW971 (69%)212Reference Group
Smoking historyNo848 (60%)234Reference Group
Yes567 (40%)1871.22 (1.05–1.43)0.01
Tumor typeBrainb150 (11%)6970.61 (0.46–0.80)1.65 × 10−8
Breast136 (10%)2140.86 (0.67–1.11)
Colon/rectum141 (10%)1740.91 (0.69–1.19)
Hematologic201 (14%)7070.48 (0.37–0.63)
Lung160 (11%)1461.15 (0.89–1.48)
Cutaneous90 (6%)5350.59 (0.40–0.86)
Other537 (38%)177Reference Group
TMB levelLow (≤5 mutations/Mb)960 (68%)238Reference Group
Intermediate (≥6 and <20 mutations/Mb)348 (25%)1741.44 (1.21–1.71)1.8 × 10−4
High (≥20 and <50 mutations/Mb)58 (4%)1951.12 (0.75–1.67)
Very high (≥50 mutations/Mb)49 (3%)3500.73 (0.43–1.25)
VariableGroupHR (95% CI)Pa multivariateBootstrapc P multivariate
Age, y<60Reference group
≥601.54 (1.30–1.84)9.42 × 10−76.1 × 10−4
Smoking historyNoReference group
Yes1.15 (0.98–1.36)0.090.20
EthnicityAfrican-American1.06 (0.70–1.60)0.780.49
Asian1.30 (1.00–1.67)0.050.15
Hispanic1.11 (0.87–1.42)0.410.43
Other1.71 (1.19–2.47)3.9 × 10−30.05
NHWReference group
Tumor typeBrain0.61 (0.46–0.81)7.3 × 10−40.02
Breast0.93 (0.72–1.20)0.580.45
Colon/rectum0.94 (0.71–1.25)0.660.48
Hematologic0.49 (0.37–0.64)2.2 × 10−72.2 × 10−4
Lung0.97 (0.75–1.27)0.840.49
Cutaneous0.76 (0.50–1.15)0.190.29
OtherReference group
TMB levelLow (≤5 mutations/Mb)Reference group
Intermediate (≥6 and <20 mutations/Mb)1.29 (1.07–1.54)5.4 × 10−30.05
High (≥20 and <50 mutations/Mb)0.98 (0.63–1.50)0.900.49
Very high (≥50 mutations/Mb)0.65 (0.36–1.35)0.150.25
  • Note: All survival data are calculated from the time of advanced disease; patients with local disease only were not included in the analysis unless they had brain tumors or hematologic malignancies that were considered advanced disease at diagnosis.

  • aBolded P values represent P ≤ 0.05, or equivalent significance with Bonferroni correction for multiple hypotheses as appropriate in multivariate analysis. Results demonstrated that tiered TMB confers an increased risk of death with intermediate-range TMB, which returns to baseline risk at higher levels, even trending toward a protective effect at “high” and “very high” TMB tier (Supplementary Table S1 is a similar analysis that includes immunotherapy-treated patients). P value for multilevel factor variables in univariable analysis derived from likelihood ratio test.

  • bBrain tumors included 83 high-grade tumors, 70 grade III or less, and 7 nonglial tumors.

  • cBootstrapped P values were generated using random resampling to create 1,000 computer-generated datasets.