Toxicity profiles of antibody-drug conjugates for anticancer treatment: a systematic review and meta-analysis
Yukio Suzuki1,2, Susu Zhou3, Yukihide Ota2,4
1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Background:
Antibody-drug conjugates are attractive targeted agents in anticancer treatment because of their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with antibody-drug conjugates, despite tens of clinical trials.
Methods:
A systematic review of randomized controlled trials evaluating antibody-drug conjugate efficacy in anticancer treatment was conducted. PubMed, EMBASE, and ClinicalTrial.gov were searched for relevant studies. Meta-analyses assessed the odds ratios (ORs) of 12 treatment-related symptoms and toxicities in patients treated with antibody-drug conjugates compared with those receiving other anticancer agents without antibody-drug conjugates. All-grade and high-grade (grade ≥3) toxicities were examined.
Results:
Twenty studies involving 10 075 patients were included. Compared with control groups, antibody-drug conjugates were associated with a higher risk of all-grade fatigue (OR = 1.25, 95% confidence interval [CI] = 1.08 to 1.45), anorexia (OR = 1.36, 95% CI = 1.09 to 1.69), nausea (OR = 1.46, 95% CI = 1.09 to 1.97), and sensory neuropathy (OR = 2.18, 95% CI = 1.27 to 3.76) as treatment-related symptoms. Patients treated with antibody-drug conjugates had a statistically significantly lower risk of all-grade febrile neutropenia (OR = 0.46, 95% CI = 0.22 to 0.96). Conversely, they had a higher risk of thrombocytopenia (OR = 2.07, 95% CI = 1.00 to 4.31), increased alanine aminotransferase (OR = 2.51, 95% CI = 1.84 to 3.40), and increased aspartate aminotransferase (OR = 2.83, 95% CI = 2.04 to 3.93). Subgroup analysis showed a similar toxicity profile when comparing the solid tumors with hematologic malignancy groups and the antibody-drug conjugate vs antibody-drug conjugate plus chemotherapy groups, except for some neurologic and hematologic adverse events.
Conclusions:
This comprehensive profile of adverse events associated with antibody-drug conjugate-based treatment shows an increase in various types of all-grade treatment-related symptoms and adverse events, although no increase in high-grade adverse events was seen.
Insights
Antibody-drug conjugates increase risks for side effects like fatigue and nausea, but not severe ones. This systematic review analyzes adverse events in 10,075 patients, finding a mixed toxicity profile for these targeted anticancer agents.
Area of Science:
- Oncology
- Pharmacology
Background:
- Antibody-drug conjugates (ADCs) are targeted anticancer therapies with potential for reduced toxicity.
- The full spectrum of adverse events associated with ADCs is not well-characterized despite numerous clinical trials.
Approach:
- A systematic review and meta-analysis of randomized controlled trials was performed.
- Searches included PubMed, EMBASE, and ClinicalTrials.gov to identify relevant studies.
- The analysis assessed treatment-related symptoms and toxicities in patients receiving ADCs versus control agents.
Key Points:
- ADCs were linked to increased all-grade fatigue, anorexia, nausea, and sensory neuropathy.
- A lower risk of all-grade febrile neutropenia was observed with ADCs.
- Increased risks of thrombocytopenia and elevated liver enzymes (ALT, AST) were associated with ADCs.
Conclusions:
- ADCs are associated with a higher incidence of various all-grade treatment-related symptoms and adverse events.
- No significant increase in high-grade (≥3) adverse events was detected in patients treated with ADCs.
- The findings provide a comprehensive profile of ADC-associated toxicities, aiding clinical management.
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