Real-world utilization of PD-1/PD-L1 inhibitors with palliative radiotherapy in patients with metastatic non-small cell lung cancer

Abstract

Background: Programmed cell death protein 1 (PD-1) blockade plus radiotherapy may be a promising strategy to improve the prognosis of patients with metastatic non-small cell lung cancer (NSCLC). However, the optimum combined scheme, treatment time of radiotherapy, and irradiated lesion have not been fully determined.

Methods: A total of 321 metastatic NSCLC patients treated with immunotherapy were identified. Among them, 107 patients received PD-1/PD-ligand 1 (PD-L1) inhibitors with radiotherapy, while the remaining cases did not receive radiotherapy. Data on overall survival (OS), progression-free survival (PFS), treatment response and adverse events were collected. Comparisons based on type of radiation, timing of radiotherapy and number of irradiated lesions were performed.

Results: The median OS in PD-1/PD-L1 inhibitors plus radiotherapy was longer than in nonradiotherapy (22.8 vs. 16.6 months, p = 0.022). The median PFS showed a similar trend in this study (9.4 vs. 6.2 months, p = 0.042). Moreover, the combined strategy demonstrated a superior disease control rate and abscopal control rate versus without radiotherapy (both p ≤ 0.001). Further multivariate analysis in the immunotherapy and radiotherapy groups revealed that age below 65 (p = 0.004), Eastern Cooperative Oncology Group performance scores of 0-1 (p = 0.001), oligometastasis (p = 0.006), concurrent combination (p = 0.002), and treated with SRT (p = 0.013) were associated with longer OS. There was a similar incidence of adverse events between the two groups (both p ≥ 0.05).

Conclusions: The combination of PD-1/PD-L1 inhibitors plus palliative radiotherapy demonstrated favorable survival and good tolerability in metastatic NSCLC patients.

Keywords: immunotherapy; non-small cell lung cancer; radiotherapy.

FIGURE 1

Kaplan–Meier curves and bar graph illustrating the overall survival (OS), progression‐free survival (PFS), abscopal response rates (ARR), and abscopal disease control rates (ACR) of 321 patients with metastatic non‐small cell lung cancer (NSCLC), stratified according to the treatment received. (a,b) Patients who treated with PD‐1/PD‐L1 inhibitors plus radiotherapy showed superior OS and PFS (OS: 22.8 vs. 16.6 months, p = 0.022; PFS: 9.4 vs. 6.2 months, p = 0.042). (c,d) Patients receiving PD‐1/PD‐L1 inhibitors plus radiotherapy showed higher ACR (92.5% vs. 77.1%, p ≤ 0.001), while no statistical difference in ARR (41.1% vs. 36.9%, p = 0.465). (e–l) In PD‐1/PD‐L1 inhibitors plus radiotherapy group, longer OS and PFS were noted in patients who were diagnosed as oligometastasis (OM) compared with multiple metastasis (MM) (OS: 27.5 vs. 15.7 months, p = 0.002; PFS: 12.5 vs. 7.1 months, p ≤ 0.001), treated with SRT (OS: 30.6 vs. 20.9 months, p = 0.031; PFS: 13.9 vs. 8.3 months, p = 0.013), and adopted concurrent modality (OS: 24.1 vs. 16.5 months, p = 0.007; PFS: 11.4 vs. 7.4 months, p = 0.031). Patients treated with multiple‐site radiotherapy showed a trend to have improved OS and PFS (OS: NR vs. 21.4 months, p = 0.064; PFS: 15.4 vs. 9.0 months, p = 0.145)