May 2024: The Food and Drug Administration has officially approved selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of advanced or metastatic RET fusion-positive thyroid cancer in both adult and pediatric patients aged 2 years and older. This approval is specifically for patients who require systemic therapy and have not responded to radioactive iodine treatment (if applicable).
Selpercatinib obtained expedited approval for this specific use in patients aged 12 and above in 2020.
The efficacy of the treatment was assessed in the LIBRETTO-001 (NCT03157128) clinical trial, which involved 65 patients with RET fusion-positive thyroid cancer. These patients were refractory to radioactive iodine (RAI) treatment, if it was a suitable option, and had not received any systemic therapy before, or had been previously treated in different groups.
The primary metrics of effectiveness were the overall response rate (ORR) and the duration of response (DOR). The objective response rate (ORR) was 85% (95% confidence interval [CI]: 71%, 94%) in the group of 41 patients who had received previous treatment, and 96% (95% CI: 79%, 100%) in the group of 24 patients who had not had systemic medication before. The median duration of response (DOR) was 26.7 months (95% confidence interval [CI]: 12.1, not evaluable [NE]) in the patients who had received previous treatment, and NE (95% CI: 42.8, NE) in the patients who had not received systemic medication before.
The study LIBRETTO-121 (J2G-OX-JZJJ; NCT03899792) provided evidence supporting the effectiveness of selpercatinib in treating RET fusion-positive thyroid cancer in 10 pediatric and young adult patients. This study is an international, single-arm, multi-cohort clinical trial that looks at how selpercatinib can help kids and young adults with solid tumors that have become RET-altered. The objective response rate (ORR) was 60% with a 95% confidence interval (CI) ranging from 26% to 88%. Furthermore, 83% of the participants had a response duration of at least 12 months.
The predominant side effects (≥25%) included swelling, gastrointestinal distress, exhaustion, oral dryness, high blood pressure, stomach discomfort, difficulty passing stools, skin irritation, queasiness, and head pain. The most prevalent laboratory abnormalities in Grade 3 or 4 were lymphocyte depletion, elevated alanine aminotransferase (ALT), elevated aspartate aminotransferase (AST), reduced salt levels, and reduced calcium levels.
The body surface area of pediatric patients aged 2 to less than 12 years determines the appropriate dosage of selpercatinib. For those who are 12 years of age and older, the dosage depends on the patient’s weight. Refer to the prescribed instructions for precise details on dosage.
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.
