Dr Patel on Toxicities Associated With Immunotherapy-Based Combinations in NSCLC

“When we think about these [combination] therapies, their potential for durable remissions in metastatic disease is so profound that finding a way to get patients safely on immunotherapy is important.”

Sandip P. Patel, MD, a professor of medicine in the Department of Medicine at the University of California, San Diego (UCSD) and a medical oncologist at the UCSD Moores Cancer Center, discussed toxicities to be aware of when using immunotherapy-based combination regimens in patients with advanced non–small cell lung cancer (NSCLC). He also highlighted the current role of antibody-drug conjugates (ADCs) in the NSCLC treatment paradigm, as well as ways this class of agents may evolve in the future.

When considering immunotherapy-related toxicities, it is important to recognize that the addition of any therapeutic agent to a regimen inherently increases the risk of adverse effects (AEs), Patel began. For instance, the incorporation of cytotoxic chemotherapy introduces a well-known spectrum of toxicities, including gastrointestinal (GI) disturbances (e.g., nausea), alopecia, and hematologic complications like neutropenia, anemia, and thrombocytopenia, he said. Similarly, the inclusion of immune checkpoint inhibitors, particularly CTLA-4 inhibitors, is associated with an increased incidence and severity of immune-related AEs. Among these, GI toxicities like immune-mediated colitis are of notable concern.

Despite the expanded toxicity profile associated with combination regimens, the potential for durable responses and long-term disease control in metastatic NSCLC makes it imperative to find safe strategies to initiate and maintain patients on immunotherapy, Patel emphasized. Personalizing immunotherapy selection based on PD-L1 expression levels, molecular alterations, and the patient’s overall disease burden allows oncologists to appropriately counsel patients and caregivers about potential AEs and implement early intervention strategies to mitigate serious complications, he reported.

Moreover, the advent of ADCs has marked a transformative advancement in the management of NSCLC, Patel continued. Agents like datopotamab deruxtecan-dlnk (Datroway), which targets TROP2, and telisotuzumab vedotin-tllv (Emrelis), which targets MET, have gained regulatory approval in the refractory metastatic setting. These therapeutics represent a precision delivery system of cytotoxic agents directly to tumor cells. Although ADCs predictably produce toxicities attributable to both their antibody component and chemotherapy payload, they may also give rise to unanticipated AEs, such as interstitial lung disease, which can be serious or even fatal if not detected early, he explained.

Understanding the unique toxicity profiles of ADCs is critical, especially given that these agents are used in heavily pretreated patient populations who may have diminished physiological reserves, according to Patel. Nevertheless, for appropriately selected patients, ADCs have demonstrated promising efficacy, including central nervous system activity, reinforcing the need to identify optimal strategies for safe and effective delivery of these novel treatments in clinical practice, he concluded.