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. Author manuscript; available in PMC: 2018 Aug 1.
Published in final edited form as: Clin Cancer Res. 2017 Mar 28;23(15):4242–4250. doi: 10.1158/1078-0432.CCR-16-3133

Table 1.

Patient characteristics (N = 155)1

Variables All
(N=155)
TTF
<2 months (N=49)
TTF
≥2 months (N=106)
Odds- ratio *
(95% CI)
(Univariate)
p-value *
(Univariate)
Odds- ratio #
(95% CI) (Multivariate)
p-value #
(Multivariate)
p-value §
(Bootstrap)
Age ≤ 65 years 104 (67.1%) 32 (65.3%) 72 (67.9%) 0.89 (0.44–1.80) 0.85
Age > 65 years 51 (32.9%) 17 (34.7%) 34 (32.1%)
Cancer diagnosis
Melanoma 51 (32.9%) 6 (12.2%) 45 (42.5%) 0.19 (0.08–0.48) 0.0002 0.12 (0.01–0.74) 0.02 0.004
Non-small cell lung cancer 38 (24.5%) 18 (36.7%) 20 (18.9%) 2.50 (1.17–5.32) 0.03 1.33 (0.44–4.00) 0.75 0.56
Squamous cell carcinoma of head and Neck 11 (7.1%) 4 (8.2%) 7 (6.6%) 1.26 (0.39–4.25) 0.74
Cutaneous squamous cell carcinoma 9 (5.8%) 0 (0) 9 (8.5%) <0.26 (0.02–1.77) 0.06 0.85 (0–7.36) 0.91 0.001
Renal cell carcinoma 6 (3.9%) 3 (6.1%) 3 (2.8%) 2.24 (0.50–9.82) 0.38
Colorectal cancer 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
Types of immunotherapy
Anti-PD-1 or PD-L1 102 (65.8%) 39 (79.6%) 63 (59.4%) 2.66 (1.19–5.72) 0.02 0.37 (0.05–2.50) 0.39 0.19
Anti-CTLA-4 alone or in combination with anti-PD-1 35 (22.6%) 5 (10.2%) 30 (28.3%) 0.29 (0.12–0.76) 0.01 0.84 (0.12–7.40) 1.00 0.74
High-dose IL2 10 (6.5%) 3 (6.1%) 7 (6.6%) 0.92 (0.25–3.66) >0.9999
Investigational agents 8 (5.2%) 2 (4.1%) 6 (5.7%) 0.71 (0.14–2.95) >0.9999
Genomic alterations
TP53 65 (41.9%) 24 (49.0%) 41 (38.7%) 1.52 (0.78–2.99) 0.29
CDKN2A/B 46 (29.7%) 12 (24.5%) 34 (32.1%) 0.69 (0.31–1.50) 0.45
TERT 37 (23.9%) 7 (14.3%) 30 (28.3%) 0.42 (0.16–1.05) 0.07 1.68 (0.43–6.62) 0.57 0.47
BRAF 28 (18.1%) 8 (16.3%) 20 (18.9%) 0.84 (0.35–1.99) 0.82
LRP1B 19 (12.3%) 4 (8.2%) 15 (14.2%) 0.54 (0.19–1.67) 0.43
PTEN 16 (10.3%) 2 (4.1%) 14 (13.2%) 0.28 (0.06–1.14) 0.10 0.26 (0.02–1.54) 0.19 0.06
MYC 15 (9.7%) 5 (10.2%) 10 (9.4%) 1.09 (0.40–3.20) >0.9999
NF1 14 (9.0%) 1 (2.0%) 13 (12.3%) 0.15 (0.01–0.85) 0.07 0.26 (0.01–2.27) 0.37 0.17
PIK3CA 14 (9.0%) 6 (12.2%) 8 (7.5%) 1.71 (0.54–5.50) 0.37
KRAS 12 (7.7%) 3 (6.1%) 9 (8.5%) 0.70 (0.20–2.79) 0.75
MLL2 12 (7.7%) 2 (4.1%) 10 (9.4%) 0.41 (0.09–1.66) 0.34
NOTCH1 11 (7.1%) 0 (0) 11 (10.4%) <0.19 (0.02–1.22) 0.02 0.55 (0–3.67) 0.63 0.003
NRAS 11 (7.1%) 1 (2.0%) 10 (9.4%) 0.20 (0.02–1.24) 0.18
ARID2 10 (6.5%) 1 (2.0%) 9 (8.5%) 0.22 (0.02–1.46) 0.17
EGFR 10 (6.5%) 8 (16.3%) 2 (1.9%) 10.2 (2.28–48.3) 0.002 8.36 (1.28–98.5) 0.02 0.004
CTNNB1 9 (5.8%) 3 (6.1%) 6 (5.7%) 1.09 (0.29–4.08) >0.9999
APC 8 (5.2%) 3 (6.1%) 5 (4.7%) 1.32 (0.34–5.29) 0.71
ARID1A 8 (5.2%) 2 (4.1%) 6 (5.7%) 0.71 (0.14–2.95) >0.9999
ASXL1 8 (5.2%) 1 (2.0%) 7 (6.6%) 0.29 (0.03–1.74) 0.44
BRCA2 8 (5.2%) 2 (4.1%) 6 (5.7%) 0.71 (0.14–2.95) >0.9999
CCND1 8 (5.2%) 2 (4.1%) 6 (5.7%) 0.71 (0.14–2.95) >0.9999
FGFR1 8 (5.2%) 4 (8.2%) 4 (3.8%) 2.27 (0.63–8.02) 0.26
PTCH1 8 (5.2%) 1 (2.0%) 7 (6.6%) 0.29 (0.03–1.74) 0.44
SETD2 8 (5.2%) 2 (4.1%) 6 (5.7%) 0.71 (0.14–2.95) >0.9999
ATM 7 (4.5%) 2 (4.1%) 5 (4.7%) 0.86 (0.17–4.25) >0.9999
NOTCH2 7 (4.5%) 2 (4.1%) 5 (4.7%) 0.86 (0.17–4.25) >0.9999
RB1 7 (4.5%) 3 (6.1%) 4 (3.8%) 1.66 (0.40–6.38) 0.68
RET 7 (4.5%) 3 (6.1%) 4 (3.8%) 1.66 (0.40–6.38) 0.68
SMAD4 7 (4.5%) 2 (4.1%) 5 (4.7%) 0.86 (0.17–4.25) >0.9999
BAP1 6 (3.9%) 3 (6.1%) 3 (2.8%) 2.24 (0.50–9.82) 0.38
CREBBP 6 (3.9%) 0 (0) 6 (5.7%) <0.42 (0.04–3.24) 0.18
ERBB2 6 (3.9%) 2 (4.1%) 4 (3.8%) 1.09 (0.20–4.79) >0.9999
FAT1 6 (3.9%) 1 (2.0%) 5 (4.7%) 0.42 (0.04–3.24) 0.67
GNAS 6 (3.9%) 1 (2.0%) 5 (4.7%) 0.42 (0.04–3.24) 0.67
MCL1 6 (3.9%) 2 (4.1%) 4 (3.8%) 1.09 (0.20–4.79) >0.9999
MDM2/4 6 (3.9%) 6 (12.2%) 0 (0) >11.9 (1.53–141.6) 0.001 10.8 (1.88-infinity) 0.02 0.001
PDGFRA 6 (3.9%) 1 (2.0%) 5 (4.7%) 0.42 (0.04–3.24) 0.67
SOX2 6 (3.9%) 4 (8.2%) 2 (1.9%) 4.62 (1.04–24.7) 0.08 1.56 (0.14–22.0) 1.00 0.49
STK11 6 (3.9%) 1 (2.0%) 5 (4.7%) 0.42 (0.04–3.24) 0.67
CD274 (PD-L1) 5 (3.2%) 0 (0) 5 (4.7%) <0.53 (0.04–3.36) 0.18
DNMT3A 5 (3.2%) 4 (8.2%) 1 (0.9%) 9.33 (1.46–115.1) 0.03 13.9 (1.11–783.2) 0.04 0.04
ERBB4 5 (3.2%) 0 (0) 5 (4.7%) <0.53 (0.04–3.36) 0.18
FBXW7 5 (3.2%) 3 (6.1%) 2 (1.9%) 3.39 (0.67–19.4) 0.33
FGF19 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
FGF3 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
FGF4 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
FGF6 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
JAK2 5 (3.2%) 0 (0) 5 (4.7%) <0.53 (0.04–3.36) 0.18
KDM6A 5 (3.2%) 0 (0) 5 (4.7%) <0.53 (0.04–3.36) 0.18
MET 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
PBRM1 5 (3.2%) 2 (4.1%) 3 (2.8%) 1.46 (0.25–7.33) 0.65
PDCD1LG2 5 (3.2%) 0 (0) 5 (4.7%) <0.53 (0.04–3.36) 0.18
ZNF217 5 (3.2%) 0 (0) 5 (4.7%) <0.53 (0.04–3.36) 0.18
Absolute lymphocyte count (mm3) (N=152) ¥
All (N=152) TTF < 2 months (N=48) TTF ≥2 months (N=104) Odds- ratio* p-value* (Univariate)
< 1,000 48 (31.6%) 18 (37.5%) 30 (28.8%) 1.48 (0.73–3.09) 0.35
≥ 1,000 104 (68.4%) 30 (62.5%) 74 (71.2%)
Royal Marsden Hospital score (N=133) **
All (N=133) TTF < 2 months (N=40) TTF ≥2 months (N=93) Odds- ratio* p-value* (Univariate)
0 or 1 86 (64.7%) 22 (55%) 64 (68.8%) 0.55 (0.26–1.20) 0.17
2 or 1 47 (35.3%) 18 (45%) 29 (31.2%)
MD Anderson Cancer Center prognostic score (N=133) **
All (N=133) TTF < 2 months (N=40) TTF ≥2 months (N=93) Odds- ratio* p-value* (Univariate)
0 or 1 31 (23.3%) 7 (17.5%) 24 (25.8%) 0.61 (0.24–1.51) 0.37
2 to 5 102 (76.7%) 33 (82.5%) 69 (74.2%)
*

Odds-ratio and p-value by Fisher’s exact test.

#

Odds-ratio and p-value by exact conditional logistic regression (multivariate) analysis. Included characteristics with p-value ≤ 0.1 from univariate analysis.

§

Bootstrapping with multiple logistic regression analysis was conducted on characteristics with p-value ≤ 0.1 from univariate analysis. p-value based on 982 bootstrap samples.

Anti-CTLA-4 alone; N=19, anti-CTLA-4 in combination with ant-PD-1; N=16. Among patients who received anti-CTLA-4 alone, 3 patients had TTF <2 months. Among patients receiving combination of anti-CTLA-4/PD-1, 2 patients had TTF <2 months.

If a variable dichotomized as N versus zero, and the odds ratio was thus zero or infinity, we adjusted the events to be 1 (instead of zero) versus N-1. This produces a numerical odds ratio, which is less than the actual infinite odds ratio. For example, for MDM2/4, where there were N = 6 versus zero patients with TTF<2 versus ≥2 months, the actual odds ratio is infinity. Using the adjustment above, the numeric odds ratio for N = 5 versus one patient is 11.9 and we list it as “>11.9.” The p-value shown is the actual p-value for the unadjusted numbers.

¥

Total of N=152 were tested for lymphocyte count within 4 weeks of starting the immunotherapy.

**

N=133 were evaluable for Royal Marsden Hospital score and MD Anderson Cancer Center prognostic score. For Royal Marsden Hospital score, each point was counted when albumin was <3.5 (g/dl), LDH > upper limit of normal (175 U/L) and number of organ metastases > 2. For MD Anderson Cancer Center prognostic score, each point was counted when albumin was <3.5 (g/dl), LDH > upper limit of normal (175 U/L), number of organ metastases > 2, gastrointestinal tumor type, and ECOG PS ≥ 1.

1

Included variables with N ≥ 5.

Abbreviations: CI = confidence interval; IL2 = interleukin-2; TTF = time-to-treatment failure.