3.1. Baseline Characteristics
A total of 282 patients were included in the analyses. The median age of the cohort was 61 (IQR 53-67), and 64.5% of the patients were male. Most (69.5%) of the patients were treated with nivolumab due to availability, and 84.4% were treated in the second or later lines. 45.5% of the patients had an ECOG performance status of 0. Sixty-two (22%) patients were treated with chemotherapy (CT) or targeted therapy (TT) and ICI combinations. 32.9 % of the patients had liver metastasis at baseline (Table-1).
82 (29.1%) patients were treated with ICIs beyond progression. While radiotherapy was added to treatment in 47.5% of the patients, 36.6% of patients received ICIs without further additional treatment. Baseline characteristics were largely similar between TBP and non-TBP groups other than younger median age (60 vs. 61 years, p=0.046) and an increased percentage of combination therapy use (30.5 vs. 18.5%, p=0.027) in the TBP group. Additionally, there was a trend toward an increased percentage of female patients in the TBP group (43.9 vs. 32%, p=0.058) (Table-2). In Kaplan-Meier analyses, the median time until first progression (PFS) was similar in the TBP and non-TBP groups (5.69 vs. 3.45 months, p=0.136) (Figure-2).
3.2. Univariate Analyses for Post-Progression Survival
The median follow-up after the first PD was 19.19 (95% CI: 16.08-22.30) months. During this follow-up, 196 patients died (69.5%). The post-PD survival of all cohort was 6.64 (95% CI: 4.32-8.95) months. The post-PD survival was significantly longer in patients treated with ICIs beyond progression (TBP group) compared to the non-TBP group (13.18 vs. 4.63 months, p<0.001) (Figure-2). In addition to TBP, patients with better performance status (ECOG 0 vs. >0, p=0.020), patients with lower LDH levels (<2xULN vs. >2xULN, p=0.009), patients with higher albumin levels (vs. <4 gr/dL, p=0.015) had better survival after first-progression. In contrast, the survival difference did not reach statistical significance in patients with or without liver metastases at baseline (p=0.759), treatment with ICI monotherapy, or combination with CT or TT (p=0.604).
3.3. Multivariate Analyses for Post-Progression Survival
In multivariate analyses conducted with a model including ECOG status, LDH and albumin levels, and TBP with ICIs, patients treated with ICIs beyond progression had improved survival compared non-TBP group (HR: 0.500, 95% CI: 0.349-0.717, p<0.001). Additionally, the OS remained significantly better in patients with lower LDH or higher albumin levels in multivariate analyses (Table-3). Additional sensitivity analyses according to tumor type (HR: 0.492, p<0.001), treatment line (HR: 0.502, p<0.001) and patient age (HR: 0.521, p<0.001) demonstrated a consistent benefit of TBP. The higher patient age was associated with lower post-progression survival in the alternative model including age in addition to statistically significant parameters in univariate analyses (HR: 1.013, 95% CI: 1.001-1.024, p=0.034). Furthermore, additional analyses after excluding patients who were given additional treatments (radiotherapy or chemotherapy) concomitantly with ICIs demonstrated a consistent benefit of ICI use beyond progression (HR: 0.420, 95% CI: 0.233-0.758, p=0.004). Similarly, the ICI use beyond PD was associated with improved post-progression survival (HR: 0.600, 95% CI: 0.380-0.947, p=0.028) in the additional analyses after excluding patients with no further treatment after PD.