Dr Malhotra on Persisting Knowledge Gaps Surrounding the Use of ADCs in Lung Cancer

"Many of these ADCs have camptothecin as their payload, which we know has some efficacy in the brain. We don't very well understand how the ADCs may impact tumor in the brain, or how they have their CNS efficacy, but in most of the clinical trials with the ADCs, we have seen some clinical efficacy in the brain"

Jyoti Malhotra, MD, MPH, interim division chief of Thoracic Medical Oncology, associate professor in the Department of Medical Oncology & Therapeutics Research, and the director of thoracic medical oncology at City of Hope, discussed current data on antibody-drug conjugate (ADC) efficacy in patients with non–small cell lung cancer (NSCLC) brain metastases, as well as gaps in this knowledge that still need to be addressed through future study.

Malhotra highlighted that a significant proportion of these advanced therapeutic agents utilize camptothecin as their cytotoxic payload, a compound already well-recognized for its demonstrable efficacy within the brain.

Despite these promising signals, Malhotra emphasized that the precise manner in which ADCs exert their influence on brain tumors, and the full extent of their CNS efficacy, remains poorly understood. This lack of mechanistic clarity represents a significant knowledge gap. Nevertheless, the aggregate data from most clinical trials involving ADCs consistently indicate some level of clinical efficacy in the brain, underscoring their potential as a treatment modality for this challenging patient population.

Another critical area requiring further rigorous investigation is to gain a deeper understanding of the exact mechanism of action and the specific extent to which ADCs impact efficacy in the brain, Malhotra stated. Such detailed knowledge is crucial for optimizing treatment regimens and predicting patient responses. Furthermore, an important clinical question that currently lacks a clear answer pertains to which patients can safely delay upfront radiation treatment for brain metastasis when they are already receiving an ADC. Malhotra anticipates that more comprehensive data emerging from ongoing and future studies will be essential in providing clarity on this matter.