Abstract
Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.44; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.
Highlights
Cancer treatment has been radically altered by programmed cell death-ligand 1 (PD-L1) inhibitors and programmed cell death 1 (PD-1) over the last few decades [1]
A total of 31 randomized controlled trials (RCTs) [2,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33] about PD-1/L1 inhibitors, chemotherapy, or their combination for the treatment of solid cancer were included in this network meta-analysis (NMA)
We categorized the three treatment regimens into five subgroups according to different types of Immune check inhibitors (ICIs): chemotherapy, PD-1 monotherapy, PD-1 plus chemotherapy, programmed cell death-ligand 1 (PD-L1) monotherapy, and PD-L1 plus chemotherapy
Summary
Cancer treatment has been radically altered by programmed cell death-ligand 1 (PD-L1) inhibitors and programmed cell death 1 (PD-1) over the last few decades [1]. Cancer treatment has been radically altered by programmed cell death-ligand 1 PD-1/L1 inhibitors alone (I) or combined with chemotherapy (I+C) appear to further improve clinical efficacy compared with conventional chemotherapy (C) [2,3,4,5]. PD-1/L1 inhibitors reactivate T cell-mediated anticancer immunity by inhibiting the PD-1 or PD-L1 immune checkpoint pathway [6]. In cases where cellular immunity is reactivated, these checkpoint inhibitors may cause inflammation-related side effects defined as immune-related adverse events (irAEs) [7]. Traditional chemotherapy may facilitate an immunostimulatory impact through targeting cancer cells [10] and altering whole-body physiology [11]. Chemotherapeutic drugs appear to have immunosuppressive impacts [13] due to their cytotoxic and cytostatic functions on different immune cell subpopulations. We can speculate that immunosuppression, caused by chemotherapy, may lower the risk of immune-mediated pneumonitis
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