Activity of ALK Inhibitors in Renal Cancer with ALK Alterations: A Systematic Review

Renal cell carcinoma (RCC) associated with anaplastic lymphoma kinase (ALK) gene rearrangements (ALK-RCC) is currently considered an emerging or provisional tumor entity by the last World Health Organization classification published in 2016. Although several studies assessing ALK-RCC's clinical and histological characteristics have been published in recent years, only a few publications have evaluated the activity of ALK inhibitors (ALK-i) in this subgroup of patients. Considering the well-recognized efficacy of this evolving class of targeted therapies in other ALK-positive tumors, we conducted a systematic review to evaluate the reported activity of ALK-i in the ALK-RCC subtype. MEDLINE was searched from its inception to 7 January 2022 for case reports and case series on adult metastatic ALK-RCC patients treated with ALK-i whose therapeutic outcomes were available. A virtual cohort of ALK-RCC patients was created. Our results showed a favorable activity of first- and second-generation ALK-i in pretreated ALK-RCC patients in terms of either radiological response or performance status improvement. We hope that the present work will prompt the creation of large, multi-institutional clinical trials to confirm these promising early data.

Automated summary

This study evaluated the activity of ALK inhibitors in ALK-rearranged renal cell carcinoma (ALK-RCC) and found that first- and second-generation ALK inhibitors showed favorable activity in pretreated ALK-RCC patients in terms of radiological response and performance status improvement. The results suggest the potential of ALK inhibitors as a targeted therapy for ALK-RCC.