On September 27, 2024, the Food and Drug Administration conferred traditional approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult and pediatric patients aged 2 years and older diagnosed with advanced or metastatic medullary thyroid cancer (MTC) harboring a RET mutation, as identified by an FDA-sanctioned assay, necessitating systemic therapy.
Selpercatinib obtained expedited clearance for this indication for patients aged 12 years and older in 2020. On May 29, 2024, the FDA conferred expedited clearance for this indication to pediatric patients aged 2 years and older.
The efficacy was assessed in LIBRETTO-531 (NCT04211337), a randomized, multicenter, open-label trial involving adults and adolescents with advanced or metastatic RET-mutant medullary thyroid carcinoma (MTC). Patients were randomized in a 2:1 ratio to receive either selpercatinib (160 mg bi-day) or the physician’s option of cabozantinib (140 mg daily) or vandetanib (300 mg daily). Patients were categorized according to RET mutation (M918T against others) and the expected treatment if assigned to the control group (cabozantinib versus vandetanib).
The primary effectiveness endpoint was progression-free survival (PFS), assessed by a blinded independent review committee in accordance with RECIST v1.1. The median progression-free survival (PFS) was not reached (NR) (95% confidence interval: not evaluable [NE], NE) in the selpercatinib cohort, while it was 16.8 months (95% confidence interval: 12.2, 25.1) in the cabozantinib/vandetanib cohort (Hazard Ratio 0.280 [95% confidence interval: 0.165, 0.475], p-value <0.0001).
The therapeutic efficacy of selpercatinib was corroborated by a pre-defined study of patient-reported comparative side effect impact; participants in the selpercatinib group experienced reduced duration of severe side effect distress compared to those treated with cabozantinib or vandetanib.
The predominant adverse effects (≥25%) included hypertension, edema, xerostomia, tiredness, and diarrhea. The predominant Grade 3 or 4 laboratory abnormalities (≥5%) included diminished lymphocytes, elevated alanine aminotransferase (ALT), reduced neutrophils, heightened alkaline phosphatase (ALP), increased blood creatinine, lowered calcium, and elevated aspartate aminotransferase (AST).
The advised selpercatinib dosage for pediatric patients aged 2 to under 12 years is determined by body surface area, while for patients aged 12 years and over, it is based on weight. Refer to the prescription information for detailed dosing guidelines.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
