Table 3.
Univariate and multivariate analysis of factors affecting outcome for patients with all tumor types excluding melanoma and NSCLC treated with immunotherapy agents (TMB low or intermediate vs. high) (N = 63)*
| Variable | Group (N) | PR/CR N (%) | OR (95% CI)1 | P–value univariate (PR/CR)2 | P-value multivariate (PR/CR) | Median PFS (mos)3 | HR (95% CI) (PFS)1 | P-value univariate (PFS)4 | p-value multivariate (PFS) | Median OS (mos)3 | HR (95% CI) (OS)1 | P-value univariate (OS)4 | P-value multivariate (OS) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | ≤60 years (N = 33) | 4 (12%) | 0.38 (0.12–1.35) | 0.2017 | 3.4 | 1.44 (0.82–2.54) | 0.2033 | 11.1 | 1.25 (0.60–2.65) | 0.5449 | |||
| >60 years (N = 30) | 8 (27%) | 2.64 (0.74–8.55) | 2.7 | 0.69 (0.39–1.22) | 11.2 | 0.80 (0.39–1.66) | |||||||
| Gender | Men (N = 41) | 11 (27%) | 7.7 (1.11–86.57) | 0.0433 | 0.219 | 2.9 | 0.70 (0.38–1.29) | 0.2128 | 11.1 | 1.23 (0.56–2.69) | 0.6085 | ||
| Women (N = 22) | 1 (5%) | 0.13 (0.01–0.90) | 3.5 | 1.43 (0.78–2.63) | Not reached (median f/u of 5.4 mos) | 0.81 (0.37–1.77) | |||||||
| Ethnicity | Caucasian (N = 40) | 10 (25%) | 3.50 (0.77–17.00) | 0.1830 | 0.254 | 3.6 | 0.64 (0.35–1.18) | 0.1179 | 0.499 | 11.2 | 0.63 (0.29–1.38) | 0.2047 | |
| Hispanic (N = 7) | 0 (0%) | 0 (0–2.58) | 0.3292 | 1.9 | 1.38 (0.52–3.65) | 0.4515 | 3.1 | 2.82 (0.76–10.44) | 0.0168 | 0.053 | |||
| Asian (N = 7) | 1 (14%) | 0.68 (0.05–5.40) | 1.0000 | 2.0 | 1.62 (0.57–4.56) | 0.2597 | Not reached (median f/u of 3.7 mos) | 1.15 (0.32–4.07) | 0.8179 | ||||
| African American (N = 6) | 1 (17%) | 0.70 (0.06–5.51) | 1.0000 | 5.0 | 1.047 (0.41–2.69) | 0.9212 | Not reached (median f/u of 6.0 mos) | 0.80 (0.22–2.97) | 0.7625 | ||||
| Other (N = 3) | 0 (0%) | 0 (0–4.99) | 1.0000 | 3.6 | 1.66 (0.38–7.21) | 0.3849 | Not reached (median f/u of 8.6 mos) | 0.72 (0.13–4.05) | 0.7491 | ||||
| TMB | Low to Intermediate (N = 46) | 4 (9%) | 0.11 (0.03–0.44) | 0.0016 | 0.006 | 2.1 | 3.31 (1.86–5.91) | 0.0007 | 0.003 | 11.1 | 1.88 (0.84–4.22) | 0.1847 | 0.362 |
| High (N = 17) | 8 (47%) | 9.33 (2.28–31.23) | 10.0 | 0.30 (0.17–0.54) | 11.2 | 0.53 (0.24–1.20) | |||||||
| Type of immunotherapy | Anti-PD-1/PD-L1 monotherapy (N = 55) | 9 (16%) | 0.33 (0.06–1.43) | 0.1700 | 0.120 | 2.9 | 0.97 (0.38–2.48) | 0.9477 | 11.2 | 1.23 (0.46–3.28) | 0.6633 | ||
| Other immunotherapy5 (N = 8) | 3 (38%) | 3.07 (0.70–15.99) | 2.6 | 1.03 (0.40–2.63) | 25.4 | 0.81 (0.31–2.17) |
All univariate P values of ≤0.2 were included in the multivariate analysis. For a similar analysis by TMB low vs. intermediate to high, see Supplemental Table 5. For an analysis of melanoma and NSCLC on their own, see Supplemental Tables 20–23. Tumors included: Adrenal carcinoma (n=1), appendix adenocarcinoma (n=1), basal cell carcinoma (n=2), bladder transitional cell carcinoma (n=4), breast cancer (n=3), cervical cancer (n=2), colon adenocarcinoma (n=5), cutaneous squamous cell carcinoma (n=8), hepatocellular carcinoma (n=3), head and neck (n=13), Merkel cell carcinoma (n=2), ovarian carcinoma (n=2), pleural mesothelioma (n=1), prostate cancer (n=1), renal cell carcinoma (n=6), sarcoma (n=3), thyroid cancer (n=3), unknown primary squamous cell carcinoma (n=2), and urethral squamous cell carcinoma (n=1)
Odds Ratio (OR) >1.0 implies higher chance of response; Hazard Ratio (HR) <1.0 implies less chance of progression or death
Calculated using Fisher’s exact test
All medians for PFS and OS calculated by Kaplan Meier
Calculated using log-rank (Mantel-Cox) test
Other immunotherapy: OX40 (n=2), anti-CD73 (n=1), anti-CTLA4 (n=2), OX40+anti-PD-L1 (n=1), anti-CTLA4/anti-PD-1/PD-L1 (n=1), and IDO+anti-PD-1/PD-L1 (n=1)
Abbreviations: CI = confidence interval; CR = complete response; CTLA4 = cytotoxic T-lymphocyte associated protein 4; HR = hazard ratio; IL2 = interleukin 2; OR = odds ratio; OS = overall survival; PD-1 = programmed death receptor-1; PD-L1 programmed death receptor-ligand 1; PD = progressive disease: PFS = progression free survival; PR = partial response; TMB = tumor mutational burden