David DiBardino, MD, on the Rationale for Intratumoral Therapy in Lung Cancer

David M. DiBardino, MD, an interventional pulmonologist and associate professor of clinical medicine at the University of Pennsylvania's Perelman School of Medicine, breaks down the scientific rationale for intratumoral therapy, an emerging strategy that concentrates antitumor agents directly inside a tumor rather than delivering them systemically.

DiBardino traces the concept back to melanoma and non–small cell lung cancer (NSCLC), 2 of the "immune hot" tumor types that led the way in systemic immunotherapy. Even though targeted therapy and immunotherapy have transformed outcomes for some patients with these cancers, a persistent gap remains: many patients with immune-sensitive tumors still do not respond to systemic treatment, and simply increasing systemic dosing tends to drive toxicity rather than efficacy. Intratumoral therapy grew out of a logical next question, DiBardino says: what if more drug could be delivered directly to the tumor instead of throughout the body?

Melanoma led the field because superficial skin and lymph node lesions are relatively easy to access and inject. Lung cancer lagged behind despite an arguably greater unmet need, DiBardino explains, largely because lung tumors move with respiration and historically lacked reliable localization techniques for bronchoscopic or percutaneous injection. Advances in intraprocedural imaging and equipment localization have since narrowed that gap.

DiBardino also details why standardizing intratumoral drug delivery remains a "clean slate" for the field. Open questions include appropriate dosing and concentration, whether an injected agent stays retained in the tumor or leaks into systemic circulation, and whether a tumor's capsule can tolerate additional injected volume without complications. He points to a cautionary tale from melanoma research, where some assets that looked promising in phase 1 and phase 2 trials failed in phase 3 studies that may have used injection protocols too loosely defined to reliably deliver the agent as intended.