Immune checkpoint inhibitors beyond first-line progression with prior immunotherapy in patients with advanced non-small cell lung cancer

Abstract

Background: Immunotherapy, monotherapy, and immunotherapy plus platinum-based chemotherapy are the standard treatments for advanced non-small cell lung cancer (NSCLC) patients with negative driver genes. However, the impact of similar continuing immunotherapy beyond progression (IBP) of first-line immunotherapy for advanced NSCLC has not yet been shown. This study aimed to estimate the impact of immunotherapy beyond first-line progression (IBF) and evaluate the factors associated with second-line efficacity.

Methods: Ninety-four cases of advanced NSCLC patients with progressive disease (PD) post first-line treatment with platinum-based chemotherapy plus immunotherapy and administrated prior immune checkpoint inhibitors (ICIs) between November 2017 and July 2021 were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression analyses were applied to determine predictive factors independently associated with second-line efficacity.

Results: A total of 94 patients were incorporated in this study. Patients who continued the original ICIs after initial PD were defined as IBF (n=42), whereas those who discontinued immunotherapy were defined as non-IBF (n=52). The second-line objective response rates (ORR, ORR = CR + PR) of patients in the IBF and non-IBF groups were 13.5% vs. 28.6%, respectively (P=0.070). No significant survival difference was found between patients in the IBF and non-IBF groups in first-line median progression-free survival (PFS) (mPFS1, 6.2 vs. 5.1 months, P=0.490), second-line median PFS (mPFS2, 4.5 vs. 2.6 months, P=0.216), or median overall survival (OS) (mOS, 14.4 vs. 8.3 months, P=0.188). However, the benefits inPFS2 were observed in individuals performed PFS1 >6 months (group A) than those of PFS1 ≤6 months (group B) (median PFS2, 4.6 vs. 3.2 months, P=0.038). Multivariate analyses did not reveal any independent prognostic factors for efficacy.

Conclusions: The benefits of continuing prior ICIs administration beyond first-line immunotherapy progression might not be obvious in patients with advanced NSCLC, but those first line treatment showed a longer period may receive efficacy benefits.

Keywords: Non-small cell lung cancer (NSCLC); efficacy; immune checkpoint inhibitors (ICIs); immunotherapy beyond progression (IBP).

Figure 1

Flow chart of specific screening process. NSCLC, non-small cell lung cancer; PD, progressive disease; ICIs, immune checkpoint inhibitors; IBF, immunotherapy beyond first-line progression; Non-IBF, non-immunotherapy beyond first-line progression.

Figure 2

Response of patients to second-line treatment. Outcomes were not statistically different in ORR between non-IBF and IBF (13.5% vs. 28.6%, P=0.070). ORR, objective response rate; IBF, immunotherapy beyond first-line progression; non-IBF, non-immunotherapy beyond first-line progression; NA, not evaluated; PD, progressive disease; SD, stable disease; PR, partial response.

Figure 3

Kaplan-Meier curves of PFS1 (A), PFS2 (B), and OS (C) of all patients. Median PFS1, 5.3 months (95% CI: 4.1–6.6 months); median PFS2, 3.0 months (95% CI: 1.9–4.1 months); median OS, 10.5 months (95% CI: 5.0–15.9 months). PFS1, the free-progression survival of the first-line; PFS2, the free-progression survival of the second-line; OS, overall survival; 95% CI, 95% confidence interval.

Figure 4

Kaplan-Meier curves of PFS1 (A), PFS2 (B), and OS (C) of patients in IBF and non-IBF groups. No statistically significant differences in PFS1, PFS2, and OS (median PFS1, 6.2 vs. 5.1 months, P=0.490; median PFS2, 4.5 vs. 2.6 months, P=0.216; median OS, 14.4 vs. 8.3 months, P=0.188). PFS1, the free-progression survival of the first-line; PFS2, the free-progression survival of the second-line; OS, overall survival; IBF, immunotherapy beyond first-line progression; non-IBF, non-immunotherapy beyond first-line progression; 95% CI, 95% confidence interval.

Figure 5

Kaplan-Meier curves of PFS2 (A) and OS (B) of patients in groups A (PFS1 ≤6 months) and B (PFS1 >6 months). Patients with longer survival (group B) in first-line immunotherapy had better PFS than patients with shorter survival times (group A) (median PFS2, group A vs. group B, 3.2 vs. 4.6 months, P=0.038). No significant differences in OS were observed between group A and B (median OS, 10.4 vs. 18.0 months, P=0.221). PFS1, the free-progression survival of the first-line; PFS2, the free-progression survival of the second-line; OS, overall survival; IBF, immunotherapy beyond first-line progression; non-IBF, non-immunotherapy beyond first-line progression.

Figure 6

Forest plot of the IBF group. HR, hazard ratio; IBF, immunotherapy beyond first-line progression; ECOG, Eastern Cooperative Oncology Group; PFS1, the free-progression survival of the first-line.