Table 4.
Outcomes of 232 patients who received immunotherapy*
| Characteristics | Median PFS (95% CI) (months) univariate |
HR (95% CI) univariate |
P value univariate |
HR (95% CI)) multivariate** |
P value multivariate |
|---|---|---|---|---|---|
| Age ≥65 (n =91) versus < 65 years (N = 141) | 2.8 (2.1-3.6) versus 7.1 (3.2-11) | 2.9 (2.1-3.9) | <0.005 | 2.7 (1.9-4) | <0.005 |
| Women (N = 94) versus men (N = 138) | 3.8 (2.6-4.8) versus 5.7 (4.1-7.3) | 1.3 (1-1.8) | 0.07 | 1 (0.7-1.4) | 0.9 |
| STK11 mutated (N = 21) versus wild type (N = 211) | 3.2 (1-5.3) versus 4.7 (3.6-5.8) | 1.2 (0.8-2.0) | 0.4 | ||
| STK11 mutated NSCLC (N = 9) versus STK11 wild type lung cancer (N =49) | 5.5 (1.2-9.9) versus 3 (1.3-4.7) | 1.5 (1.1-2.2) | 0.3 | ||
| Lung cancer (N = 58) versus not (N = 174) | 3.6 (2.3-4.8) versus 5.1 (3.8-6.4) | 1.6 (1.1-2.2) | 0.005 | 1.5 (1.02-2.4) | 0.04 |
| Patients with >4 co-alterations versus (≤ 4 co-alterations *** | 4.7 (3.6-5.2) versus 5.1 (2.7-7.5) | 1.1 (0.9-1.5) | 0.8 | ||
| TMB high (N = 47) versus low-intermediate (N = 118) **** | 9.7 (1.5-17.9) versus 4.4 (3.6-5.2) | 0.6 (0.4-0.9) | 0.02 | 0.7 (0.4-.8) | 0.006 |
| STK11 and KRAS co-altered (N=6) versus STK11 wild-type and KRAS mutated (N=28) | 1.9 (0.2-3.9) versus 4.1 ((3.9-4.6) | 1.7 (0.9-2.4) | 0.02 | 1.9 (1-3.8) | 0.04 |
| STK11 and KRAS co-altered (N=6) versus STK11 altered and KRAS Wild type (N = 15) | 1.9 (0.1-3.9) versus 7.1 (0.1-15) | 2.9 (1-9) | 0.04 | 1.3 (0.6-3.1) | 0.5 |
| STK11 and KRAS co-altered cancers other than NSCLC (N=3) versus STK11 wild type and KRAS-mutated cancers other than NSCLC (N=17) | 1.9 (0.7-3.2) versus 5.5 (1.2-9.9) | 1.2 (0.4-3.2) | 0.7 | ||
| STK11 and KRAS co-altered NSCLC (N=3) versus STK11 wild type and KRAS mutated NSCLC (N=11) | 2.1 (0.9-3) versus 3 (1.9-4.2) | 1.6 (0.8-2.5) | 0.1 | 2.1 (1.9-3.4) | 0.3 |
| Characteristics | Median OS (95% CI) (months) univariate***** |
HR (95% CI) univariate |
P value univariate |
HR (95% CI)) multivariate |
P value multivariate |
| Age ≥65 (n =91) versus < 65 years (N = 141) | 7.5 (6-9.2) versus 29 (21.8-36.2) | 12.5 (7.7-20.4) | <0.005 | 12.5 (7-22) | <0.005 |
| Women (N = 94 versus men (N = 138) | 14.8 (10.9-18.8) versus 26.9(21-28.9) | 1.5 (1.02-2.2-) | 0.04 | 1.04 (0.7-1.7) | 0.9 |
| STK11 mutated (N = 21) versus wild type (N = 211) | 17.7 (10.2-25.2) versus 18 (11.2-21.5) versus | 1.2 (0.6-2.3) | 0.7 | ||
| STK11 mutated NSCLC (n = 9) versus STK11 wild type lung cancer (N = 49) | 11.4 (2.4-20.5) versus 12.8 (8.2-22.1) | 1.4 (1.2-2.2) | 0.04 | 1.3 (1.1-2.4) | 0.2 |
| Lung cancer (N = 58) versus not (N = 174) | 11.1 (1.7-20.5) versus 21 (15.3-24.1) | 1.7 (1.1-2.5) | 0.02 | 1.3 (0.7-2.2) | 0.3 |
| Patients with >4 co-alterations versus (≤ 4 co-alterations ** | 15.8 (12.9-23.4) versus 17.5(11.3-21.5) | 1.6 (0.5-3.6) | 0.6 | ||
| TMB high (N = 47) versus low-intermediate (N = 118) **** | 37.3 vs 15.8 | 0.7 (0.4-1.3) | 0.02 | 0.5 (0.3-0.9) | 0.01 |
| STK11 and KRAS co-altered (N=6) versus STK11 wild type and KRAS mutated (N=28) | 9.3 (2.4-16.3) versus 16.3 (10.8-21.8) | 1.2 (0.8-2) | 0.4 | ||
| STK11 and KRAS co-altered (N=6) versus STK11 altered and KRAS wild type (N = 15) | 9.3 (2.4-16.3) versus 17.2 (11.6-22.8) | 2.97 (1-9)) | 0.06 | 2 (0.2-3.6) | 0.5 |
| STK11 and KRAS co-altered cancers other than NSCLC (N=3) versus STK11 wild type and KRAS mutated cancers other than NSCLC (N=17) | 18.7 (2.3-23) versus 23.1 (1.9-8.4) | 1.9 (0.8-2.5) | 0.08 | 2.1 (0.7-3.3) | 0.3 |
| STK11 and KRAS co-altered NSCLC (N=3) versus STK11 wild type and KRAS mutated NSCLC (N=11) | 11.9 (1.6-17.3) versus 12.4 (10.7-37.2) | 1.3 (0.7-2.1) | 0.4 |
Examples of drugs included in immunotherapy were anti-PD-1/PD-L1 agents, anti-CTLA4, combination anti-CTLA4/anti-PD-1/PD-L1 regimens, and high dose interleukin-2 (IL-2).
Variables with p value <0.25 for association with PFS were included in the multivariate analysis. PFS is from first immunotherapy; the small numbers of patients in some rows precludes robust statistical analysis
Co-alterations were stratified at the median (≤ 4 versus >4) determined in Table 2.
TMB values were available for only 165 patients: TMB low to intermediate includes <20 mutations per megabase; TMB high, ≥ 20 mutations/mb.
OS is from initiation of the first immunotherapy to patient death.
Abbreviations: CI = confidence interval; HR = hazard ratio; PFS = progression-free survival; TMB = tumor mutational burden