How Do ADCs Affect Safety and QOL in Breast Cancer?

TOPLINE:

Antibody-drug conjugates (ADCs) were associated with a higher risk for all-grade adverse events (AEs) in metastatic breast cancer than standard therapy, according to a meta-analysis. However, these drugs delayed deterioration in quality of life in almost all domains.

METHODOLOGY:

• Researchers conducted a meta-analysis of nine randomised controlled trials evaluating ADCs vs standard therapy in metastatic breast cancer.
• The analysis included a total of 5753 patients who were randomly assigned to receive ADCs (n = 3227) or standard therapy (n = 2526).
• Researchers evaluated three approved antibody-drug conjugates: Trastuzumab-emtansine, trastuzumab-deruxtecan, and sacituzumab-govitecan.
• The study outcomes were the relative risk for AEs, the discontinuation rate due to toxicity, and the impact on quality of life according to the European Organization for Research and Treatment of Cancer Quality of Life of Cancer Patients scale and its subdomains.

TAKEAWAY:

• The most common AEs (of any grade) with trastuzumab-emtansine vs standard therapy included thrombocytopenia (relative risk [RR], 7.14) and increased alanine transaminase levels (RR, 2.04).
• The most common AEs for trastuzumab-deruxtecan vs standard therapy were nausea (RR, 2.39) and anaemia (RR, 1.55), whereas sacituzumab-govitecan was associated with a higher risk for neutropenia (RR, 1.30), diarrhoea (RR, 3.62), nausea (1.90), and alopecia (2.33) than standard therapy.
• Compared with standard therapy, trastuzumab-deruxtecan and sacituzumab-govitecan delayed the onset of pain and fatigue and the clinical deterioration of global health status (hazard ratio [HR], 0.61; 95% CI, 0.50-0.75 and HR, 0.80; 95% CI, 0.69-0.93, respectively) and physical, emotional, and social functioning.
• Compared with standard treatments, none of the ADCs were associated with an increased risk for discontinuation due to AEs.

IN PRACTICE:

The authors wrote, “In the present systematic review and meta-analysis, we analysed the safety of ADCs currently approved for the treatment of metastatic breast cancer by comparing the most updated results of nine RCTs. As compared to standard therapy, ADCs were globally associated with a higher risk of all-grade AEs.” They added, “none of the ADCs were correlated with a significantly higher risk of treatment discontinuation due to AEs compared to the standard of care, nor with a faster deterioration in QOL in almost all domains.”

SOURCE:

The study was led by Marta Perachino, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. It was published online on February 13, 2025, in the European Journal of Clinical Investigation.

LIMITATIONS:

The randomised controlled trials included in the analysis investigated ADCs at different stages of the disease, with an increased risk for AEs among highly pretreated patients. As the data were collected from trials involving highly selected patients with limited comorbidities, the results could not be precisely applied to the real-world setting.

DISCLOSURES:

The authors did not disclose any funding information. Marta Perachino reported receiving honoraria from Daiichi Sankyo. Some authors reported receiving research funding or having other ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.