What is the difference in efficacy between serputinib/serpatinib and platinib?

Selpercatinib (trade name: Retevmo) and platinib (Pralsetinib, trade name: Gavreto) are two targeted drugs currently widely used in the world to treat RET gene fusion-positive cancers. Both are highly selective RET inhibitors, mainly suitable for non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer. However, there are still certain differences between the two in terms of drug mechanism, efficacy data, safety and clinical application. This article will analyze the differences in efficacy between these two drugs and provide a reference for patients and clinicians.

First of all, from the perspective of their mechanism of action, both seputinib and platinib are small molecule RET kinase inhibitors with high selectivity. The RET fusion gene is considered to be a key mutation driving a variety of malignant tumors. Therefore, targeted inhibition of the RET signaling pathway can effectively control tumor progression. Although the pharmacological classification of the two is similar, in the early molecular design of seputinib, more consideration was given to the penetration of the blood-brain barrier, which was shown in its clinical trials to have stronger control over patients with brain metastases. Platinib has a slightly different molecular structure design and different sensitivities to partial resistance mutations, and may show advantages in certain complex mutation backgrounds.

Secondly, in terms of clinical efficacy, the representative study of seputinib is the LIBRETTO-001 clinical trial, which showed that in patients with RETfusion-positive non-small cell lung cancer, its objective response rate (ORRORR span>) is as high as 64%-85%, the median progression-free survival (PFS) can reach more than 17 months, and it also shows stable efficacy in patients with central nervous system metastasis. Platinib is represented by the ARROW study. In patients with RET fusion-positive non-small cell lung cancer, ORRis about61%-70%, and PFS can reach about 16 months. There is not much difference between the two in terms of overall efficacy indicators, but seputinib may be slightly better at controlling brain metastases, so it is more suitable for patients with central metastases.

In terms of safety and tolerability, both seputinib and platinib demonstrated good safety profiles. According to existing clinical data, common adverse reactions of seputinib include hypertension, elevated liver enzymes, fatigue, diarrhea, etc., and the incidence of serious adverse events is low. Adverse reactions of platinib mainly include anemia, neutropenia, and increased creatine kinase. In general, adverse effects of both can be managed through dose adjustment or adjuvant therapy. However, it should be noted that platinib may be more prone to myelosuppression in some patients, while seputinib imposes higher requirements on blood pressure management. Therefore, when selecting drugs, doctors need to make judgments based on the patient's underlying disease and tolerance.

Finally, in terms of clinical scope of application, both drugs have been approved by the USFDA for the treatment of RET fusion-positive non-small cell lung cancer, RETmutation-positive medullary thyroid carcinoma (MTC), and RETfusion thyroid cancer that is refractory to radioactive iodine therapy. Both support the use of first-line or late-line treatment. However, due to differences in research data, the evidence for the use of seputinib in brain metastases and complex mutation indications is more sufficient, while platinib is also favored by some doctors because of its potential coverage of some drug-resistant mutations.

In summary, seputinib and platinib are generally equivalent in terms of mechanism, efficacy, and safety, but each has its own emphasis. Seputinib has better performance in brain metastasis control and tolerability, and is suitable for patients with brain metastases or patients who require long-term medication; while platinib may have advantages in certain drug-resistant mutations. For patients, the decision on which drug to choose should be based on individualized molecular test results, disease characteristics and doctor's recommendations in order to obtain the best treatment effect.

Reference materials:https://en.wikipedia.org/wiki/Selpercatinib