Over the past two decades, numerous complex cancer therapies called antibody drug conjugates (ADCs) have been tested in clinical trials and approved for use in patients. An analysis of multiple scientific databases has found that some ADCs have higher rates of adverse effects. The findings were reported in the journal CANCER.
An ADC has a complex structure comprised of a monoclonal antibody (MoAb) that targets a protein expressed on cancer cells, a toxic compound to kill the targeted cells (also called a payload or warhead), and a linker to join the two. The clinical efficacy and toxicity of ADCs are affected by each component. Data have established that ADCs as anticancer therapeutics have a unique mechanism of action, which includes the targeted delivery and release of its payload at the tumours site through MoAb antibody components, thus exerting simultaneous roles as both targeted therapy and chemotherapy
In 2000, gemtuzumab ozogamicin was the first ADC approved by the US Food and Drug Administration, and more than a dozen ADCs have been approved worldwide to date. To investigate the side effects associated with different ADCs, a team led by Prof Hong Zhu of Xiangya Hospital, Central South University, in China, conducted a systematic review and meta-analysis of published clinical trials of ADCs that reported treatment-related toxicities.
The researchers found 2511 records of 169 relevant trials involving 22 492 patients. The incidence of treatment-related adverse events was 91.2% for all events and 46.1% for serious adverse events (grade 3 or higher). The most common adverse events overall were lymphopenia, nausea, neutropenia, vision blurriness, and peripheral neuropathy. The most common serious adverse events were neutropenia, hypaesthesia, thrombocytopenia, neutropenia with fever, and lymphopenia. Certain ADCs were linked with higher average incidences of adverse events.
“Different ADCs appear to vary in their treatment-related adverse events. Our results provide an important reference for clinicians and patients on how to address ADCs’ toxicity in clinical practice,” said Prof Zhu.
Source: Wiley
