Adverse Events Associated With Antibody-Drug Conjugates Across Cancer Types

Treatment with antibody-drug conjugates may increase the risk of certain adverse events (AEs) in patients with cancer, according to a meta-analysis published in JNCI Cancer Spectrum.

Researchers found that antibody-drug conjugates, when compared to other cancer treatments or placebo, were associated with an increased risk of hepatic, gastrointestinal, ocular, and other AEs.

This meta-analysis included 10,075 patients treated in 20 randomized, phase 2-3 trials comparing antibody-drug conjugates to other treatments or to placebo.

The studies enrolled patients with breast cancer (n=6), lymphoma (n=5), small cell lung cancer (n=3), acute lymphoblastic leukemia (n=1), gastric cancer (n=1), glioblastoma (n=1), mesothelioma (n=1), renal cell carcinoma (n=1), and ovarian cancer (n=1).

In 2 of the studies, the control intervention was placebo. In the remaining 18 studies, the control treatment was an unconjugated antibody, hormone therapy, or cytotoxic/targeted therapy.

In 15 studies, an antibody-drug conjugate was evaluated alone. In 7 studies, it was combined with other anticancer agents. The antibody-drug conjugates studied were trastuzumab emtansine (n=5), brentuximab vedotin (n=4), rovalpituzumab tesirine (n=2), inotuzumab ozogamicin (n=2), trastuzumab deruxtecan (n=1), depatuxizumab mafodotin (n=1), anetumab ravtansine (n=1), AGS-16C3F (n=1), IMGN901 (n=1), mirvetuximab soravtansine (n=1), and sacituzumab govitecan (n=1).

Results

There were no significant differences in the risk of high-grade AEs between patents who received antibody-drug conjugates and patients who did not. However, there were a range of all-grade AEs that were more common among patients who received antibody-drug conjugates.

The researchers identified 4 “clinically relevant” treatment-related AEs of any grade that were significantly more likely for patients who received antibody-drug conjugates. They were fatigue, anorexia, nausea, and sensory neuropathy, as seen in the table below.

Treatment-Related AEs of Any Grade
Event	Incidence, antibody-drug conjugates	Incidence, control interventions	Odds ratio (OR)
Fatigue	35.3%	30.5%	1.25; 95% CI, 1.08-1.45; P =.002
Anorexia	18.1%	13.7%	1.36; 95% CI, 1.09-1.69; P =.006
Nausea	41.7%	33.3%	1.46; 95% CI, 1.09-1.97; P =.01
Sensory neuropathy	21.3%	13.8%	2.18; 95% CI, 1.27-3.76; P =.005

There was no increased risk of cardiovascular AEs or renal AEs among patients who received antibody-drug conjugates. However, there was an increased risk of ocular, hepatic, gastrointestinal, and other AEs.

The all-grade AEs that were significantly more likely among patients receiving antibody-drug conjugates were:

• Thrombocytopenia (OR, 2.07; 95% CI, 1.00-4.30)
• Increased alanine aminotransferase (OR, 2.51; 95% CI, 1.84-3.40)
• Increased aspartate aminotransferase (OR, 2.83; 95% CI, 2.04-3.93)  
• Cataracts (OR, 3.92; 95% CI, 1.52-10.13)
• Eye pain (OR, 9.54; 95% CI, 2.64-34.46)
• Photophobia (OR, 6.84; 95% CI, 2.26-20.67)
• Blurred vision (OR, 3.12; 95% CI, 1.02-9.55)
• Epistaxis (OR, 2.45; 95% CI, 1.50-4.01)
• Abdominal pain (OR, 1.29; 95% CI, 1.01-1.66)
• Upper abdominal pain (OR, 1.53, 95% CI, 1.23-1.89)
• Dry mouth (OR, 4.46; 95% CI, 2.56-7.78)
• Vomiting (OR, 1.32; 95% CI,1.01-1.74)
• Gingival bleeding (OR, 6.50, 95% CI, 2.80-15.12)
• Headache (OR, 1.49; 95% CI,1.24-1.79)
• Peripheral motor neuropathy (OR, 3.91; 95% CI, 1.14-13.42).

Several AEs were less likely to occur among patients receiving antibody-drug conjugates. These were hot flashes (OR, 0.57; 95% CI, 0.37-0.88), febrile neutropenia (OR, 0.46; 95% CI, 0.22-0.96), leukopenia (OR, 0.47; 95% CI, 0.29-0.77), lymphopenia (OR, 0.69; 95% CI, 0.48-0.98), and neutropenia (OR, 0.56; 95% CI, 0.31-1.01).

“To the best of our knowledge, this is the first study to comprehensively compare the tolerability of ADC [antibody-drug conjugate]-based regimens with other standard treatments across multiple malignancies,” the researchers wrote. “While our results provide valuable information for clinicians to balance the benefits and risks of treatment options in their decision-making, it is crucial to consider the limitations of our study, particularly the heterogeneity of included studies, when applying these findings to clinical practice.”

Disclosures: One of the study authors declared affiliations with Merck. Please see the original reference for a full list of disclosures.

Reference

Suzuki Y, Zhou S, Ota Y, et al. Toxicity profiles of antibody drug conjugates for anticancer treatment: A systematic review and meta-analysis. JNCI Cancer Spec. Published online September 26, 2023. doi:10.1093/jncics/pkad069

This article originally appeared on Cancer Therapy Advisor