Immune-related adverse events of a PD-L1 inhibitor plus chemotherapy versus a PD-L1 inhibitor alone in first-line treatment for advanced non-small cell lung cancer: A meta-analysis of randomized control trials.

Abstract

BACKGROUND:

The addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-L1) inhibitor is a more effective option as a first-line treatment for advanced non-small cell lung cancer (NSCLC). It might also inhibit an overactive immune response and thereby reduce immune-related adverse events (irAEs). This meta-analysis assessed the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) versus a PD-(L)1 inhibitor alone (I) and evaluated the indirect relative risk (RR) of I+C versus I.

METHODS:

The protocol of this study was registered with PROSPERO (CRD42020139923). The pooled rates of irAEs at different grades were calculated by a single-arm meta-analysis weighted by sample size, and RRs were determined by direct meta-analysis and indirect treatment comparison.

RESULTS:

Overall, I+C had a lower rate of grade 3 or higher irAEs than I (7.1% vs 10.6%; indirect RR, 0.516; 95% confidence interval [CI], 0.291-0.916), although irAEs of any grade were similar. The rate of pneumonitis with I+C was lower than the rate with I for any grade (5.9% vs 7.1%; indirect RR, 0.217; 95% CI, 0.080-0.588) and for grade 3 or higher. In the endocrine system, I+C was associated with a lower overall ratein comparison with I (16.1% vs 20.1%; indirect RR, 0.260; 95% CI, 0.120-0.564), whereas irAEs of the digestive system were similar with I+C and I. In other systems, I+C decreased the rate of skin reactions, including rash, in comparison with I (10.4% vs 12.9%; indirect RR, 0.474; 95% CI, 0.299-0.751). The rate of grade 3 or higher skin reactions (excluding rash) also decreased with I+C versus I (1.1% vs 2.0%) with an indirect RR of 0.158 (95% CI, 0.032-0.765), whereas other included irAEs were similar.

CONCLUSIONS:

In comparison with a PD-(L)1 inhibitor alone, a combination with chemotherapy for the first-line treatment of NSCLC decreased the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.

LAY SUMMARY:

In the first-line treatment of advanced non-small cell lung cancer (NSCLC), the addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-(L)1) inhibitor is a more effective option. Adding chemotherapy might reduce immune-related adverse events (irAEs). Thus, this article assesses the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) in comparison with a PD-(L)1 inhibitor alone (I) and evaluates the indirect relative risk (RR) with I+C versus I. The key finding is that in comparison with a PD-(L)1 inhibitor alone, a combination with chemotherapy for the first-line treatment of NSCLC decreases the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.

• Authors: Manting Wang, Hengrui Liang, Wei Wang, Shen Zhao, Xiuyu Cai, Yi Zhao, Caichen Li, Bo Cheng, Shan Xiong, Jianfu Li, Jianxing He, Wenhua Liang
• Journal: Cancer (Cancer) Vol. 127 Issue 5 Pg. 777-786 (03 01 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 33119182 (Publication Type: Comparative Study, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Cancer Society.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Endocrine System Diseases (epidemiology)
• Humans
• Immune Checkpoint Inhibitors (adverse effects)
• Incidence
• Lung Neoplasms (drug therapy)
• Pneumonia (epidemiology)
• Randomized Controlled Trials as Topic