Dr Eroglu on Future Steps for Assessing Ceritinib Plus Trametinib in Metastatic Melanoma

Zeynep Eroglu, MD, medical oncologist, Department of Cutaneous Oncology, Moffitt Cancer Center; assistant professor, Department of Oncologic Sciences, the University of South Florida Morsani College of Medicine, discusses the future steps in an ongoing study assessing the efficacy and safety of ceritinib (Zykadia), both as monotherapy and in combination with trametinib (Mekinist), in patients with metastatic melanoma.

The objective Eroglu describers entails analytical scrutiny using methodologies such as flow cytometry and single-cell RNA sequencing to discern potential markers associated with favorable responses to ceritinib with or without trametinib, particularly in patients receiving immunotherapy as their preceding line of treatment. The overarching aim of this research is to delineate signaling pathways that may inform future therapeutic strategies, notwithstanding the specific drugs employed, by targeting markers identified in patients receiving immunotherapy as their most recent line of therapy, Eroglu says.

Eroglu notes that the challenges inherent in combining multiple TKIs underscore the importance of addressing overlapping toxicities, exemplified by the concomitant use of trametinib and ceritinib. This obstacle is not unique to the current study but resonates with findings from previous investigations, according to Eroglu.

Prospective drug development endeavors aim to mitigate these challenges by identifying newer agents with improved toxicity profiles, Eroglu explains. The overarching goal of this approach is to facilitate the development of combination therapies characterized by reduced toxicity, thereby enabling dose escalation to achieve clinically efficacious levels, Eroglu says. This approach is pivotal given the continued relevance of targeted therapy in patients with metastatic melanoma following prior treatment with anti–PD-1 therapy and adoptive cellular therapy, Eroglu emphasizes.

Eroglu's research underscores the imperative need for elucidating potential markers of therapeutic response in elderly patients with metastatic melanoma, and particularly in those who have undergone immunotherapy as their preceding line of treatment. The identification of such markers holds promise for informing future therapeutic strategies aimed at addressing the unmet needs of this patient population, Eroglu notes. Moreover, Eroglu mentioned that efforts to overcome the challenges associated with combining TKIs underscore the ongoing commitment to refining treatment approaches and improving patient outcomes in metastatic melanoma.