Dr Sands on the Evolving Role of ADCs in SCLC Management

Jacob Sands, MD, oncology medical director, International Patient Center, Dana-Farber Cancer Institute; assistant professor, Harvard Medical School, discusses the evolution of the role of antibody-drug conjugates (ADCs) in the treatment of patients with small cell lung cancer (SCLC).

ADCs represent an exciting advancement in oncology, particularly in the management of non–small cell lung cancer (NSCLC) and SCLC, Sands begins. One promising agent, ifinatamab deruxtecan, has elicited an overall response rate of 52.4% (95% CI, 29.8%-74.3%) in previously treated patients with SCLC, as well as a median PFS of 5.6 months (95% CI, 3.9-8.1). Although this agent is not a definitive therapy, its development marks a significant step forward in the SCLC field, offering durable outcomes for this aggressive disease and expanding available options, Sands explains.

The potential use of ADCs in oncology extends beyond their current use, as they may serve as backbones for future combination regimens or be integrated into earlier lines of therapy pending forthcoming data, Sands emphasizes. Although ADCs are not novel in oncology, their application in lung cancer, particularly NSCLC, is relatively recent, according to Sands. In the context of SCLC, research with rovalpituzumab tesirine (Rova-T) highlighted the challenges associated with ADCs, particularly those related to linker toxicity and efficacy, Sands says. Despite Rova-T failing to meet expectations, findings with this agent provided valuable insights into targeting DLL-3 in SCLC, paving the way for subsequent drugs in this disease, including the immunotherapy agent tarlatamab, which also targets DLL-3, Sands explains. The development of ADCs continues to be a promising area of research, and efforts are ongoing to refine these agents and expand their clinical applications, Sands reports. The success of these therapies will depend on overcoming previous challenges and building on the foundational work laid by earlier ADCs, Sands concludes.