Selpercatinib approved for cancers with a rearranged transfection gene fusion (RET).

It is a highly selective, potent, and brain penetrant  RET kinase inhibitor.

RET gene fusions drive 1 to 2% of non-small cell lung cancers and is responsible for an estimated 10,000 new cases annually worldwide.<span class=”Apple-converted-space”> </span>

RET fusions are also found in 10 to 20% of papillary thyroid cancers as well as subgroups of colorectal, and breast cancers.

The most common adverse reactions, including laboratory abnormalities, (≥ 25%) were increased aspartate aminotransferase, increased alanine aminotransferase, increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation.

The recommended selpercatinib dose is weight based—120 mg for patients less than 50 kg, and 160 mg for those 50 kg or greater.<span class=”Apple-converted-space”> </span>

Selpercatinib is taken orally twice daily with or without food; or with food when co-administered with a proton pump inhibitor.

Selpercatinib is an effective agent with manageable safety, in patients with RET-mutant medullary thyroid cancer.


Whether or not they had received previous therapy with vandetanib or cabozantinib.


Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib  in patients with RET-mutant medullary thyroid cancer (LIBRETTO investigators.

RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. 


Of the patients who had previously received treatment 69% had a response, and 73% of the patients who had not received prior treatment had a response.


The 1-year progression free survival was 82% and 92% , respectively. 


The most common grade ≥3 adverse events: included hypertension (21%), increased alanine aminotransferase (11%), increased aspartate aminotransferase (9%), hyponatremia (8%), and diarrhea (6%).


2% of patients discontinued selpercatinib due to drug-related AEs.

Treatment with selpercatinib led to a significantly longer progression free survival than  platinum based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive non-small cell lung cancer (LIBRETTO, trial investigators).



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