Efficacy of Selpercatinib in <i>RET</i>-Altered Thyroid Cancers

Wirth, Lori J.; Sherman, Eric J.; Robinson, Bruce G.; Solomon, Benjamin; Kang, Hyunseok; Lorch, Jochen H.; Worden, Francis P.; Brose, Marcia S.; Patel, Jyoti D.; Leboulleux, Sophie; Godbert, Yann; Barlési, Fabrice; Morris, John C.; Owonikoko, Taofeek K.; Tan, Daniel S.W.; Gautschi, Oliver; Weiss, Jared; Fouchardière, Christelle De La; Burkard, Mark E.; Laskin, Janessa; Taylor, Matthew H.; Kroiß, Matthias; Médioni, Jacques; Goldman, Jonathan W.; Bauer, Todd M.; Levy, Benjamin; Zhu, Viola W.; Lakhani, Nehal; Moreno, Víctor; Ebata, Kevin; Nguyen, M.; Heirich, Dana; Zhu, Edward Y.; Huang, Xin; Yang, Luxi; Kherani, Jennifer; Rothenberg, S. Michael; Drilon, Alexander; Subbiah, Vivek; Shah, Manisha H.; Cabanillas, Maria E.

doi:10.1056/nejmoa2005651

Cited by 475 publications

(362 citation statements)

References 19 publications

Supporting

Mentioning

347

Contrasting

Unclassified

Order By: Relevance

“…These patients had a 1‐year progression‐free survival of 92% 24 . This study further highlighted the adverse events associated with selpercatinib, including hypertension, transaminitis, hyponatremia, and diarrhea 24 …”

Section: Discussionmentioning

confidence: 52%

“…14 A recently published phase 1-2 trial of selpercatinib for RET-altered thyroid cancer has shown a complete or partial response in 73% of patients with RET-mutant MTC who had not previously received multikinase therapy. 24 These patients had a 1-year progression-free survival of 92%. 24 This study further highlighted the adverse events associated with selpercatinib, including hypertension, transaminitis, hyponatremia, and diarrhea.…”

Section: Discussionmentioning

confidence: 97%

“…24 These patients had a 1-year progression-free survival of 92%. 24 This study further highlighted the adverse events associated with selpercatinib, including hypertension, transaminitis, hyponatremia, and diarrhea. 24 The decision to operate on a patient with advanced disease and marked response to a RET tyrosine kinase specific inhibitor requires careful consideration after multidisciplinary input, weighing the benefit of surgery to limit potential future morbidity which may accompany tumor escape and locoregional progression, and the burden and aggressiveness of distant metastatic disease.…”

Section: Discussionmentioning

confidence: 97%

“…Biochemical assays have shown that pralsetinib, another selective RET inhibitor, inhibits the wild type RET kinase activity with an 8‐ to 28‐fold higher potency when compared with the MKI's cabozantinib, vandetanib, and RXDX‐105 14 . A recently published phase 1‐2 trial of selpercatinib for RET ‐altered thyroid cancer has shown a complete or partial response in 73% of patients with RET ‐mutant MTC who had not previously received multikinase therapy 24 . These patients had a 1‐year progression‐free survival of 92% 24 .…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Neoadjuvant selpercatinib for advanced medullary thyroid cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Targeted kinase inhibitors have been increasingly utilized in the treatment of advanced medullary thyroid cancer (MTC) over the last decade. Recently, highly potent next generation selective RET inhibitors have been clinically validated, and selpercatinib was recently Food and Drug Administration (FDA)-approved for advanced MTC. The advent of highly selective, potent RET inhibitors is broadening the treatment options for patients with RETmutated cancers. Methods: We report the first published case of neoadjuvant selpercatinib followed by surgery for a patient with initially unresectable, widely metastatic, RET-mutated MTC who was treated on a single patient protocol. Results: After greater than 50% RECIST response, the patient underwent complete surgical resection followed by selpercatinib resumption. He remains locoregionally disease-free 21 months after starting therapy with stable metastatic disease (after initial partial response); and calcitonin/CEA continue to decline. Conclusion: This novel treatment strategy for locoregionally advanced RETmutated MTC warrants further study in clinical trials.

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Neoadjuvant selpercatinib for advanced medullary thyroid cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In an interesting article recently published in NEJM, Wirth et al presented the outcome of the RET-altered thyroid cancer cohort from the LIBRETTO-001 phase 1-2 trial. 6 In the group of 55 RET-mutated medullary thyroid cancer patients previously treated with vandetanib, cabozantinib or both, the progression-free survival (PFS) at 1 year was 82% and the objective response rate (ORR) was 69% (95% CI 55% to 81%). Among 88 patients with RET-mutated medullary thyroid cancer naïve for targeted therapy the 1 year PFS was 92% (95% CI 82% to 97%) and the ORR was 73% (95% CI 62% to 82%).…”

Section: Ret-altered Thyroid Cancers: a New Paradigm For Targeted Thementioning

confidence: 99%

In the literature: October 2020

2020

View full text Add to dashboard Cite

Thyroid Cancer

Boucai,

Zafereo,

Cabanillas

2024

JAMA

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Efficacy of Selpercatinib in RET-Altered Thyroid Cancers

Cited by 475 publications

References 19 publications

Neoadjuvant selpercatinib for advanced medullary thyroid cancer

Neoadjuvant selpercatinib for advanced medullary thyroid cancer

In the literature: October 2020

Thyroid Cancer

Contact Info

Product

Resources

About