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

Abstract

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.

ALK Inhibition With Alectinib for Refractory Metastatic Renal Cell Carcinoma With ALK Rearrangement: A Rare Case Report and Literature Review

“…10 RCCs with fusion of vinculin ( VCL ) with ALK ( VCL-ALK ) have been the most well-described ALK rearrangements and occur in children with sickle cell trait. 8,11 Other recognized fusions include EML4-ALK , TPM3-ALK , STRN-ALK , HOOK1-ALK , CLIP1-ALK , KIF5B-ALK , KIAA1217-ALK , and PLEKHA7-ALK , with many having only one case of the fusion reported in the literature. 8 Therefore, we present an additional ALK fusion partner to the literature of ALK -rearranged RCC.…”

Antibody–Drug Conjugates for the Treatment of Renal Cancer: A Scoping Review on Current Evidence and Clinical Perspectives

“…The recent advances in genomics and molecular biology, along with the clarification of the cancer-immunity cycle, have profoundly changed the treatment paradigm of mRCC [ 62 ]. In the last two decades, the therapeutical management of patients affected by this malignancy has evolved from immune cytokine-based approaches (i.e., IL2 and IFN-α) to targeted therapies consisting of TKI against either vascular endothelial growth factor-receptor (VEGF-R), mammalian target of rapamycin (mTOR), or anaplastic lymphoma kinase (ALK) [ 63 , 64 ]. Moreover, the recent advent of immunotherapy with monoclonal antibodies modulating some immune checkpoints (ICI) has represented a novel breakthrough in the immunological treatment of RCC [ 62 ].…”

The Role of Histology-Agnostic Drugs in the Treatment of Metastatic Castration-Resistant Prostate Cancer

“…The advent of precision medicine has expanded the available therapeutic options in the management of genitourinary cancers [ 116 , 117 ]. Notably, the treatment paradigm of mCRPC has evolved rapidly in recent years, with the introduction of both new anti-cancer agents [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ] and more sensitive imaging methods that led to the more accurate diagnosis and staging of this type of tumor [ 3 ].…”