In a systematic review and meta-analysis reported in The Lancet Oncology, Zhou et al provided a profile of treatment-related adverse events observed in clinical trials combining PD-1 or PD-L1 inhibitors with chemotherapy, targeted therapy, immunotherapy, and radiotherapy.
Study Details
The meta-analysis included 161 clinical trials with 17,197 patients identified through May 2020 investigating globally approved PD-1 or PD-L1 inhibitors in combination with other therapies; only prospective trials reporting overall incidence or tabulated data of treatment-related adverse events were included, and trials of sequential therapy were excluded. PD-1/PD-L1 inhibitor therapy was combined with chemotherapy in 44 studies, targeted therapy in 51, another type of immunotherapy in 58, and radiotherapy in 8. Heterogeneity between studies was assessed using the I² statistic.
Key Findings
KEY POINTS
- When PD-1/PD-L1 inhibition was used in combination with chemotherapy, the incidence of treatment-related adverse events was 97.7% for any-grade adverse events and 68.3% for grade ≥ 3 adverse events.
- When used in combination with targeted therapy, the incidence was 94.5% for any-grade adverse events and 47.3% for grade ≥ 3 adverse events.
- When used in combination with another immunotherapy, the incidence was 86.8% for any-grade adverse events and 35.9% for grade ≥ 3 adverse events.
- When used in combination with radiotherapy, the incidence was 89.4% for any-grade adverse events and 12.4% for grade ≥ 3 adverse events.
When PD-1/PD-L1 inhibition was used in combination with chemotherapy, the incidence of treatment-related adverse events was 97.7% (95% confidence interval [CI] = 96.4%–98.5%; I² = 75%) for any-grade adverse events and 68.3% (95% CI = 60.7%–75.0%; I² = 93%) for grade ≥ 3 adverse events. The most common any-grade adverse event was anemia (45.4%, 95% CI = 32.4%–59.1%) and the most common grade ≥ 3 adverse event was neutropenia (19.6%, 95% CI = 13.5–27.7%).
When used in combination with targeted therapy, the incidence was 94.5% (95% CI = 90.7%–96.8%; I² = 86%) for any-grade adverse events and 47.3% (95% CI = 37.3%–57.5%; I² = 93%) for grade ≥ 3 adverse events. The most common any-grade adverse event was fatigue (34.3%, 95% CI = 27.5%–41.9%) and the most common grade ≥ 3 adverse event was hypertension (9.3%, 95% CI = 5.7%–14.9%).
When used in combination with another immunotherapy, the incidence was 86.8% (95% CI = 80.9%–91.1%; I² = 94%) for any-grade adverse events and 35.9% (95% CI = 29.5%–42.9%; I² = 92%) for grade ≥ 3 adverse events. The most common any-grade adverse event was fatigue (26.4%, 95% CI = 19.2%–35.2%) and the most common grade ≥ 3 adverse event was increased lipase (7.2%, 95% CI = 5.2%–9.9%).
When used in combination with radiotherapy, the incidence was 89.4% (95% CI = 69.0%–96.9%; I² = 74%) for any-grade adverse events and 12.4% (95% CI = 4.4%–30.6%; I² = 73%) for grade ≥ 3 adverse events. The most common any-grade adverse event was dysphagia (30.0%, 95% CI = 18.7%–44.5%) and the most common grade ≥ 3 adverse event was lymphopenia (10.3%, 95% CI = 4.5%–21.8%).
The investigators concluded, “Our study provides comprehensive data on treatment-related adverse events of different PD-1 or PD-L1 inhibitor–based combination therapies. Our results provide an essential reference of toxicity profiles of PD-1 or PD-L1 inhibitor-based combination therapies for clinicians in routine practice of cancer care.”
Yibo Gao, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Key Research and Development Programme, National Natural Science Foundation of China key program, Chinese Academy of Medical Sciences Initiative for Innovative Medicine, and others. For full disclosures of the study authors, visit thelancet.com.
