Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study

Subbiah, Vivek; Hu, Mimi I.; Wirth, Lori J.; Schüler, Martin; Mansfield, Aaron S.; Curigliano, Giuseppe; Brose, Marcia S.; Zhu, Viola W.; Leboulleux, Sophie; Bowles, Daniel W.; Baik, Christina S.; Adkins, Douglas; Keam, Bhumsuk; Matos, Ignacio; Garralda, Elena; Gainor, Justin F.; Lopes, Gilberto; Lin, Chia Chi; Godbert, Yann; Sarker, Debashis; Miller, Stephen G.; Clifford, Corinne; Zhang, Hui; Turner, Christopher D.; Taylor, Matthew H.

doi:10.1016/s2213-8587(21)00120-0

Cited by 247 publications

(208 citation statements)

References 27 publications

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“…Selpercatinib has also been approved by the EMA for patients aged ≥ 12 years, who were previously treated with cabozantinib and/or vandetanib, while pralsetinib is still awaiting a positive opinion. Pralsetinib and selpercatinib recommendations were based on multicenter, open label, multi-cohort clinical trials, ARROW, NCT03037385 [ 162 ] and LIBRETTO-001, NCT03157128, respectively, that investigated their efficacy in MTC patients with RET gene alterations. These potent inhibitors not only improved ORR, but also higher PFS and OS, with a lower rate of AEs was observed [ 162 , 163 ].…”

Section: Currently Used and Investigated Targeted Therapies In Tcsmentioning

confidence: 99%

“…Pralsetinib and selpercatinib recommendations were based on multicenter, open label, multi-cohort clinical trials, ARROW, NCT03037385 [ 162 ] and LIBRETTO-001, NCT03157128, respectively, that investigated their efficacy in MTC patients with RET gene alterations. These potent inhibitors not only improved ORR, but also higher PFS and OS, with a lower rate of AEs was observed [ 162 , 163 ]. Unfortunately, in a number of cases, there were no improvements after treatment and resistance-associated mutations were identified [ 62 , 163 , 164 ].…”

Section: Currently Used and Investigated Targeted Therapies In Tcsmentioning

confidence: 99%

“…The etiology of PPES is still unclear and its management is predominantly symptomatic with dose reduction or interruption for severe cases. Other reported muco-cutaneous AEs, such as rash, alopecia and oral stomatitis, are specifically related to inhibition of the VEGFR/EGFR pathway [ 162 , 168 ]. Proteinuria is a common renal side effect of antiangiogenic MKIs [ 166 ].…”

Section: Treatment-related Toxicitiesmentioning

confidence: 99%

“…RET-targeted therapies, based on selpercatinib and pralsetinib, seem to exhibit lower side effects than other FDA-approved treatments ( Table 5 ). The majority of patients tolerate these drugs well, while only a few percent of patients discontinue the therapy due to treatment-related AEs [ 62 , 162 , 163 ]. The most commonly observed AEs of selpercatinib are HT, diarrhoea, fatigue and dry mouth [ 163 ], whereas pralsetinib administration is associated with increased risk of neutropenia and liver impairment as well as decreased white blood cells (WBCs) count [ 162 ].…”

Section: Treatment-related Toxicitiesmentioning

confidence: 99%

“…The majority of patients tolerate these drugs well, while only a few percent of patients discontinue the therapy due to treatment-related AEs [ 62 , 162 , 163 ]. The most commonly observed AEs of selpercatinib are HT, diarrhoea, fatigue and dry mouth [ 163 ], whereas pralsetinib administration is associated with increased risk of neutropenia and liver impairment as well as decreased white blood cells (WBCs) count [ 162 ]. Overall, comprehensive education of patients to increase their awareness of signs and symptoms of possible side effects and continued monitoring is critical.…”

Section: Treatment-related Toxicitiesmentioning

confidence: 99%

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Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Ratajczak

Gawel

Godlewska

2021

IJMS

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Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.

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Section: Currently Used and Investigated Targeted Therapies In Tcsmentioning

confidence: 99%

Section: Currently Used and Investigated Targeted Therapies In Tcsmentioning

confidence: 99%

Section: Treatment-related Toxicitiesmentioning

confidence: 99%

Section: Treatment-related Toxicitiesmentioning

confidence: 99%

Section: Treatment-related Toxicitiesmentioning

confidence: 99%

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Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Ratajczak

Gawel

Godlewska

2021

IJMS

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Thyroid Cancer

Boucai,

Zafereo,

Cabanillas

2024

JAMA

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ImportanceApproximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer.ObservationsPapillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma.ConclusionsApproximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.

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Treatment for Advanced and Metastatic Thyroid Cancer Refractory to Standard Treatment—We Need to Know the When, What, and Who

Kebebew

2022

JAMA Oncol

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Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study

Cited by 247 publications

References 27 publications

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Thyroid Cancer

Treatment for Advanced and Metastatic Thyroid Cancer Refractory to Standard Treatment—We Need to Know the When, What, and Who

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