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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
- Source :
- Cancer. 127:777-786
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
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.
- Subjects :
- Cancer Research
medicine.medical_specialty
Lung Neoplasms
medicine.medical_treatment
non-small cell lung cancer (NSCLC)
Endocrine System Diseases
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
030212 general & internal medicine
Adverse effect
Lung cancer
Immune Checkpoint Inhibitors
Randomized Controlled Trials as Topic
Pneumonitis
Chemotherapy
business.industry
Incidence
Pneumonia
medicine.disease
Rash
Oncology
030220 oncology & carcinogenesis
Relative risk
medicine.symptom
business
PD-L1 inhibitor
Subjects
Details
- ISSN :
- 10970142 and 0008543X
- Volume :
- 127
- Database :
- OpenAIRE
- Journal :
- Cancer
- Accession number :
- edsair.doi.dedup.....3618cdc45a2b3b0aca739bb9cfc9c39b