A total of 209 patients with NSCLC received systemic anticancer treatment between 2015 and 2019 at Toyama University Hospital. Of these, 79 patients with tumor driver mutations, 58 patients aged < 70 years old, and 9 other patients (reasons for exclusion indicated in the figure) were excluded. Finally, data of a total of 63 patients were included in the analyses(Figure 1)༎
Table 1 shows the patient characteristics. Twenty (31.7%) and 36 (57.1%) of the NSCLC patients were diagnosed as having squamous cell carcinoma and adenocarcinoma, respectively. Other histologic types included adenosquamous carcinoma, large cell neuroendocrine cell carcinoma, and NSCLC, not otherwise specified. In all, 36 patients (57.1%) had received treatment with ICIs. Thirteen (36.1%), 19 (52.8%), and 4 (11.1%) patients received ICI therapy as 1st, 2nd, and 3rd line treatment, respectively, and 11 (30.6%), 21 (58.3%), and 4 (11.1%) patients received nivolumab, pembrolizumab, and atezolizumab, respectively.
Table 1
| | n (%) |
Age (yr) | < 75 | 30 (47.6%) |
| ≥ 75 | 33 (52.4%) |
Sex | Male | 52 (82.5%) |
| Female | 11 (17.5%) |
Histology | Squamous | 20 (31.7%) |
| Adenocarcinoma | 36 (57.1%) |
| Others | 7 (11.1%) |
PD-L1 TPS | ≥ 1% | 27 (42.9%) |
| < 1% | 22 (34.9%) |
| Unknown | 14 (22.2%) |
History of surgery | Yes | 26 (41.3%) |
| No | 37 (58.7%) |
ILD | Yes | 15 (23.8%) |
| No | 48 (76.2%) |
Disease stage | ≤III | 17 (27.0%) |
| IVA | 37 (58.7%) |
| IVB | 9 (14.3%) |
PS | 0–1 | 53 (84.1%) |
| ≥ 2 | 10 (15.9%) |
History of ICI therapy | Yes | 36 (57.1%) |
| No | 27 (42.9%) |
History of platinum therapy | Yes | 32 (50.8%) |
| No | 31 (49.2%) |
ICI, Immune checkpoint inhibitor; ILD, interstitial lung disease; PD-L1, programmed death ligand-1; PS, performance status; TPS, tumor proportion score |
Table 2 shows the association between the patient characteristics and the OS analyzed by the log-rank test. Univariate analysis identified the tumor PD-L1 status,disease stage༌and history of treatment with an ICI as being significantly associated with the OS. Figure 2 shows the Kaplan-Meier curve for the OS in the patients with and without a history of treatment with ICIs.
Table 2
Association between the patient background characteristics and the overall survival (univariate analysis)
| | OS (95% CI) | P |
Age (yr) | < 75 | 12.9 (9.2–27.4) | 0.732 |
| ≥ 75 | 11.0 (8.8–29.3) | |
Sex | Male | 12.8 (9.6–14.5) | 0.953 |
| Female | 17.2 (3.4–18.5) | |
Histology | Squamous | 9.6 (5.1–29.3) | 0.354 |
| Adenocarcinoma | 13.6 (10.7-NE) | |
| Others | 10.0 (2.7-NE) | |
PD-L1 TPS | ≥ 1% | 27.4 (12.6-NE) | 0.002 |
| < 1% | 12.9 (3.9–18.5) | |
| Unknown | 9.2 (4.2–9.8) | |
History of surgery | Yes | 14.4 (10.7-NE) | 0.262 |
| No | 9.8 (8.4–17.2) | |
ILD | Yes | 12.8 (4.9–27.4) | 0.832 |
| No | 12.6 (9.5–18.5) | |
Disease stage | ≤III | 13.6 (10.4–53.9) | 0.007 |
| IVA | 12.9 (8.8–29.3) | |
| IVB | 5.7 (2.7–11.0) | |
PS | 0–1 | 12.9 (10.4–18.5) | 0.064 |
| ≥ 2 | 5.2 (2.7–53.9) | |
History of ICI therapy | Yes | 17.2 (10.7–34.1) | 0.026 |
| No | 9.8 (4.2–14.4) | |
History of platinum therapy | Yes | 13.6 (9.2–34.1) | 0.323 |
| No | 11.0 (9.6–17.2) | |
ICI, Immune checkpoint inhibitor; ILD, interstitial lung disease; OS, overall survival; PD-L1, programmed death ligand-1; PS, performance status; TPS, tumor proportion score |
Table 3 shows the association between a history of treatment with an ICI and the OS evaluated using the Cox proportional hazards model. The PS, disease stage, history of treatment with an ICI, and history of treatment with a platinum doublet were selected as the independent variables. The tumor PD-L1 status was excluded, because there was a significant overlap between the tumor PD-L1 status and history of treatment with an ICI, even though the tumor PD-L1 status was found to be significantly associated with the OS by the log-rank test. Analysis using the Cox proportional hazards model revealed a significant association between history of treatment with an ICI and the OS.
Table 3
Association between the patient background characteristics and the overall survival (multivariate analysis)
| | HR (95% CI) | P |
PS | 0–1 | 0.31 (0.12–0.83) | 0.020 |
| ≥ 2 | 1 | |
Disease stage | ≤III | 0.37 (0.13–1.05) | 0.061 |
| IVA | 0.44 (0.19–1.03) | 0.059 |
| IVB | 1 | |
History of ICI therapy | Yes | 0.42 (0.20–0.86) | 0.019 |
| No | 1 | |
History of platinum therapy | Yes | 0.63 (0.31–1.28) | 0.202 |
| No | 1 | |
ICI, Immune checkpoint inhibitor; PS, performance status |
Table 4 shows the results of a subset analysis in patients divided into subgroups by the patient background characteristics to assess the association between history of treatment with an ICI and the OS. There was a significant interaction between the tumor histology and history of treatment with an ICI on the effect, with the association between ICI therapy and OS not being seen in patients with adenocarcinoma, but evident in those with squamous cell carcinoma and carcinoma of other histologic types.
Table 4
shows the results of a subset analysis in patients divided into subgroups by the patient background characteristics to assess the association between history of treatment with an ICI and the OS.
| | OS (95% CI) | P (log-rank test) | P (Interaction) |
| | ICI (+) | ICI (-) | | |
Age (yr) | < 75 | 27.4 (10.0-53.9) | 9.5 (2.8–14.4) | 0.060 | 0.620 |
| ≥ 75 | 12.8 (9.5–34.1) | 10.4 (3.9–18.5) | 0.141 | |
Sex | Male | 27.4 (10.7–34.1) | 9.8 (4.2–13.6) | 0.015 | 0.221 |
| Female | 17.2 (3.2–17.2) | 18.5 (3.4–18.5) | 0.433 | |
Histology | Squamous | 29.3 (7.2–53.9) | 5.5 (3.3–10.4) | 0.002 | 0.006 |
| Adenocarcinoma | 12.9 (8.8-NE) | 14.4 (4.9-NE) | 0.686 | |
| Others | 12.8 (3.4-NE) | 2.8 (2.7–2.8) | 0.008 | |
PD-L1 TPS | ≥ 1% | 27.4 (12.6-NE) | 14.5 (5.1-NE) | 0.467 | 0.983 |
| < 1% | 12.9 (3.2–34.1) | 10.4 (2.8-NE) | 0.667 | |
| Unknown | 9.5 (5.1–29.3) | 9.2 (3.3–11.0) | 0.566 | |
History of surgery | Yes | 12.9 (10.0-NE) | 14.4 (3.3–18.5) | 0.332 | 0.996 |
| No | 17.2 (8.8–29.3) | 9.2 (4.2–11.0) | 0.085 | |
ILD | Yes | 27.4 (7.2–53.9) | 9.8 (3.3–14.5) | 0.057 | 0.415 |
| No | 12.9 (9.6–34.1) | 10.4 (3.4–18.5) | 0.158 | |
Disease stage | ≤III | 27.4 (12.6–53.9) | 10.4 (3.3-NE) | 0.065 | 0.647 |
| IVA | 12.9 (8.8-NE) | 14.4 (3.4-NE) | 0.292 | |
| IVB | 5.5 (3.4–17.2) | 5.9 (2.7–11.0) | 0.624 | |
PS | 0–1 | 17.2 (12.6–34.1) | 10.4 (5.1–14.5) | 0.062 | 0.099 |
| ≥ 2 | 7.2 (3.4–53.9) | 3.4 (2.7–4.9) | 0.031 | |
History of platinum therapy | Yes | 27.4 (8.4–53.9) | 10.4 (3.9–14.5) | 0.110 | 0.844 |
No | 12.8 (9.5–29.3) | 5.9 (2.1–18.5) | 0.040 | |
ICI, Immune checkpoint inhibitor; ILD, interstitial lung disease; OS, overall survival; PD-L1, programmed death ligand-1; PS, performance status; TPS, tumor proportion score |
No significant differences in the OS were observed among patients who received ICI therapy as 1st (median: 12.6, 95% confidence interval: 5.5-NE months), 2nd (median: 29.3, 95% confidence interval: 12.8–53.9 months) and 3rd (median: 9.7, 95% confidence interval: 8.4–17.2 months) line treatment (p = 0.073, log-rank test). Furthermore, the OS was also not significantly different among patients who received ICI therapy (p = 0.807, log-rank test), including treatment with nivolumab (median: 19.5, 95% confidence interval: 3.2–53.9 months), pembrolizumab (median: 27.4, 95% confidence interval: 10.7-NE months), and atezolizumab (median: 12.9, 95% confidence interval: 10.0-NE months).