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FDA approves first treatment for lung cancer and thyroid cancer patients with specific gene mutations or fusions

FDA approves first treatment for lung cancer and thyroid cancer patients with specific gene mutations or fusions

Today (May 8th, US time), the US Food and Drug Administration (FDA) approved Retevmo (selpercatinib) capsules to treat three types of tumors: non-small cell lung cancer (NSCLC) and medullary thyroid Cancer (medullary thyroid cancer, MTC) and other types of thyroid cancer patients. The patient has a change (mutation or fusion) in a specific gene (rearranged during transfection gene, RET). Retevmo is the first approved therapy for cancer patients with RET gene changes.

Innovation in gene-specific therapies continues to rapidly advance medical practice and provide options to patients who previously had few drugs available. Dr. Richard Pazdur, director of the FDA Oncology Center of Excellence and acting director of the FDA's Office of Oncology and Diseases, Center for Drug Evaluation and Research . The FDA is committed to reviewing treatments for patients with specific subgroups of cancer, such as Retevmo.

Specifically, cancers approved by Retevmo for treatment include:

· Non-small cell lung cancer (NSCLC) that spreads in adult patients;
· Advanced medullary thyroid carcinoma (MTC) or patients who are over 12 years of age and require systemic treatment (MTC) Non-targeted treatment plan), and
advanced RET fusion-positive thyroid cancer in patients over 12 years of age who require systemic treatment, who have stopped responding to radioactive iodine (RAI) or are not suitable for radioactive iodine treatment ( RET fusion-positive thyroid cancer, RET-f + TC).

Retevmo is a kinase inhibitor that helps prevent the growth of cancer cells by blocking a class of kinases. Before implementing treatment, it is necessary to detect and identify the change state of RET gene.

The FDA approved Retevmo based on the results of clinical trials involving patients with three types of tumors. During the clinical trial, patients took 160 mg of Retevmo orally twice daily until disease progression or unacceptable toxicity. The main prognostic evaluation index is the overall response rate (ORR). The ORR reflects the percentage of patients who have reached a certain standard for tumor spread regression. The other index is the duration of response (DOR).

The efficacy of NSCLC was evaluated by 105 patients with advanced NSCLC who received platinum-based chemotherapy before, RET fusion was positive. The ORR of 105 patients was 64%. 81% of patients who responded to treatment had a DOR of more than 6 months. At the same time, the efficacy of 39 patients with RET fusion-positive NSCLC who had never received treatment was evaluated. The ORR of these patients was 84%. 58% of patients who responded to treatment had a DOR of more than 6 months.

The efficacy for adult and pediatric MTC was evaluated by RET mutant MTC patients 12 years of age and older. This study included 143 patients with advanced or metastatic RET mutant MTC. Whether they had received cabozantinib, vandetanib, or both (the same chemotherapy) in the previous period were divided into two groups. The ORR of the 55 patients who were previously treated was 69%. 76% of patients who responded to treatment had DOR over 6 months. The efficacy of 88 patients who had never received approved MTC treatment was also evaluated. The ORR of these patients was 73%. 61% of patients who responded to treatment had a DOR of more than 6 months.

(Annotation: Some people may wonder that cabozantinib, vandetanib and selpercatinib are not all tyrosine kinase inhibitors, or are they not all designed to inhibit tyrosine kinases, at least RET? Yes, when When the cancer cell RET gene begins to change and make it out of regulation, some drugs have lost their response while others are similar. Multi-target off-target and RET mutation still show specificity is the focus of attention, but clinical stage 2-3 Regardless of the effect regardless of the mechanism: it contains both positive and negative meanings, positive effects must be significant, and negative toxicity must be affordable.)

The efficacy of RET fusion positive thyroid cancer (RET-f + TC) was evaluated in adults and children aged 12 years and older. In 19 patients studied, radioactive iodine therapy (RAI, note: must be implemented as an appropriate therapy) to stop responding, and received RET-f + TC patients who had previously received another systemic treatment, and 8 cases of radioactive iodine therapy stopped responding, But RET-f + TC patients who did not receive other therapies. The ORR of the 19 patients who were previously treated was 79%. 87% of patients who responded to treatment had a DOR of more than 6 months. The ORR of 8 patients who received no treatment other than RAI was 100%. 75% of patients who responded to treatment had DOR over 6 months.

The most common adverse effects of Retevmo, are increased aspartate amino transferase (AST) and alanine amino transferase (ALT) within the liver, increased blood glucose , decreased white blood cells, decreased albumin within the blood, decreased calcium level in the blood, dry mouth, diarrhea, muscle Increased acid anhydride (a measure of kidney function), increased alkaline phosphatase (an enzyme in the liver and bones), high blood pressure, fatigue, swelling of the body or limbs, decreased platelets, increased cholesterol, rash, constipation, and decreased sodium in the blood.

Retevmo can cause serious side effects including liver toxicity (liver damage or injury), increased vital sign , prolonged QT (heart muscle takes longer than normal to fill between two beats), bleeding, and allergic reactions. If the patient has hepatotoxicity, Retevmo should be suspended, reduced, or permanently discontinued. Patients undergoing surgery should inform their doctor because drugs similar to Retevmo have caused wound healing problems.

Retevmo may cause harm to the fetus or newborn. Health professionals should advise pregnant women to pay attention to this risk, and should recommend that female patients with reproductive potential and male patients living with female partners with reproductive potential use effective contraception during treatment with Retevmo and within one week after the treatment course. In addition, women should not breastfeed during Retevmo treatment.

Retevmo is approved under the accelerated approval channel, which provides approval for drugs used to treat serious or life-threatening diseases and drugs that demonstrate significant advantages over existing therapies. The FDA also granted priority approval and breakthrough therapy certification for the project, which aims to speed up the development and review of drugs for the treatment of serious diseases when preliminary clinical evidence indicates that the drug may be significantly improved over existing therapies. In addition, Retevmo was granted orphan drug designation, which provides incentives and encourages the development of rare disease drugs.

FDA grants Retevmo's approval to Elixo's subsidiary Loxo Oncology.

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