Tyrosine kinase inhibitors rechallenge in solid tumors: a review of literature and a case description with lenvatinib in thyroid cancer

Abstract

In the last decade tyrosine kinase inhibitors (TKIs) have been employed for a wide range of hematological and solid tumors and today they represent a valid therapeutic option for different neoplasms. Among them, both sorafenib and lenvatinib were approved for the treatment of radioactive iodine (RAI) refractory differentiated thyroid carcinoma (DTC). Unfortunately, in some cases the efficacy of TKIs is limited by the onset of drug resistance after the initial response. Areas covered: We report the case of a patient with a RAI refractory advanced DTC, treated with lenvatinib after surgery, multiple RAI administrations, traditional chemotherapy, and sorafenib. During treatment with lenvatinib, a noticeable response was detected by sequential computed tomography scans but, after 27 months, tumor progression became evident and led to lenvatinib interruption. In absence of any active treatment, a further disease progression was documented, and lenvatinib was re-administered obtaining a new objective response. Starting from this case report, we review available reports about the rechallenge with TKIs in solid tumors, discussing the possible mechanisms underlying the efficacy of this approach. Expert commentary: Rechallenge with TKIs in solid tumors could be a therapeutic option in subjects with advanced and metastatic DTC who experience a progressive disease after initial response to lenvatinib.

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

“…In another study, it was stated that re-exposure to TKI after previous sunitinib and subsequent everolimus treatment may have clinical benefit, but unfortunately the sunitinib rechallenge was not explicitly reported [ 16 ]. Other case studies included in some reviews [ 8 , 17 ] were excluded from our list because they were not true rechallenges (patients were not treated with systemic drugs between sunitinib treatments, therefore they could be considered to have restarted sunitinib [ 18 ]).…”

“…The description of these hypotheses goes beyond the scope of this article. Several reviews were already published about sunitinib resistance and rechallenge in RCC [ 1 , 3 , 23 , 24 ] and Felicetti et al [ 17 ] summarized the supposed mechanisms for the transient resistance.…”

Surgical treatment of locally advanced thyroid cancer

“…With locally advanced, metastasized and histologically aggressive tumours, on the other hand, improvements in surgical outcomes will probably also depend very much on the success of molecular biology research [37]. Currently, inhibition of tumour progression has been achieved by the use of tyrosine kinase inhibitors [48][49][50]. Another promising development is the reinduction of sodium iodine symporter (NIS)-mediated radioiodine storage with the member of the mitogen-activated protein kinase (MEK) 1/2 inhibitor selumetinib.…”

Adverse reactions of sorafenib, sunitinib, and imatinib in treating digestive system tumors

“…Adverse reactions resulting from traditional chemotherapy usually manifest as nausea, vomiting, loss of appetite, diarrhea and other digestive system reactions, leukopenia, neutropenia, anemia, thrombocytopenia and other myelosuppressive reactions, oral mucositis, fatigue, hair loss, and hand‐foot and other skin changes. These adverse reactions are reported to occur in targeted therapy, but at significantly lower intensity and can be alleviated by continued treatment . Rare adverse reactions resulting from chemotherapy, such as skin color changes, rash, hypertension, water and sodium retention, and bleeding, are also known to occur in targeted therapy, but at higher incidence rates than with chemotherapy …”

“…Skin color changes to the hands and feet occurring as a result of targeted drug administration (such as sorafenib and sunitinib), referred to as the hand‐foot skin reaction (HFSR), also occur after the administration of chemotherapy drugs (such as capecitabine, fluorouracil, and doxorubicin), known as the “hand‐foot syndrome” (HFS) . HFSR and HFS may occur in the palms and soles of the feet, accompanied by tenderness, and alleviation of symptoms occurs after drug withdrawal . HFSR manifests mainly as excessive keratinization around the erythema, while HFS shows symmetrical sensory abnormalities, erythema, and edema.…”