Which one is better, bochitinib or suvotinib?

Pocitinib and suvotinib can both be used to treat non-small cell lung cancer. The efficacy of the two is similar. There is no clinical statement that which one is better. It is recommended that patients choose the most appropriate drug treatment based on their own conditions with the advice of their doctor.

Introduction to Pozitinib and Suvotinib

1. Pozitinib: is a potent tyrosine kinase inhibitor that is clinically used to treat patients with non-small cell lung cancer (NSCLC) carrying HER2 exon 20 insertion mutations. Pocitinib has activity against HER1, HER2 and HER4 mutations. It is built on an anilinoquinazoline scaffold, inhibits epidermal growth factor receptors EGFR, HER2/neu and Her 4, and covalently binds to their targets.

2. Suvotinib: It is an oral, potent, irreversible and selective EGFR tyrosine kinase inhibitor with activity against epidermal growth factor 20 protein and other mutations. Suvotinib demonstrated potent antitumor activity in both cell line and xenograft models.

Efficacy of Pocitinib in the treatment of non-small cell lung cancer

Purpose: Insertion mutations in exon 20 of the Erb-b2 receptor tyrosine kinase 2 gene (ERBB2 or HER2) occur in 2%-5% of non-small cell lung cancers (NSCLCs) and play a role as an oncogenic driver. Bochitinib, a tyrosine kinase inhibitor, was evaluated in patients with previously treated HER2 exon 20 insertion non-small cell lung cancer.

Methods: ZENITH20 is a multi-center, multi-short, open-label phase II study evaluating the efficacy of pocitinib in patients with advanced or metastatic non-small cell lung cancer. In cohort 2, patients received pocitinib (16 mg) once daily. The primary endpoint was independent review committee-assessed objective response rate (RECIST v 1.1); secondary outcome measures were disease control rate, duration of response, progression-free survival, safety and tolerability, and quality of life assessment.

Results: Between October 2017 and March 2021, 90 patients who received treatment had received a median of two treatment options. The median follow-up time was 9.0 months, and the objective response rate was 27.8%; 25 of 90 patients achieved partial response. The disease control rate is 70.0%. Most patients (74%) experienced tumor shrinkage (median shrinkage, 22%). The median progression-free survival was 5.5 months, and the median duration of response was 5.1 months.

Clinical benefit was seen regardless of the strain and type of prior treatment, the presence of central nervous system metastases, and the type of HER2 mutation.

Conclusion: Pocitinib showed anti-tumor activity in patients previously treated with HER2 exon 20 insertion non-small cell lung cancer.

Efficacy of suvotinib in the treatment of non-small cell lung cancer

Background: Suvotinib is an oral, irreversible and selective tyrosine kinase inhibitor with good safety and encouraging anti-tumor activity, as shown in a phase 1 study in patients with heavily pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations. One study evaluated the antitumor efficacy of suvotinib in patients with locally advanced or metastatic non-small cell lung cancer of the EGFR exon 20 gene who were pretreated with platinum drugs.

Methods: WU-KONG6 was a single-arm, open-label, multicenter phase 2 monotherapy trial conducted at 37 medical centers in China. Adult patients with pathologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer whose tumor tissue harbored EGFR exon 20ins mutations were recruited. All patients had received at least one prior systemic therapy, at least one of which contained platinum-based chemotherapy. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee. ORR is defined as the percentage of patients who achieve a confirmed complete or partial response on two separate assessments at least 4 weeks apart before disease progression or initiation of any new anticancer therapy. Enrolled patients received 300 mg of suvotinib once daily until they met the discontinuation criteria specified in the protocol.

Research results: Between July 19, 2021 and May 6, 2022, a total of 104 patients were enrolled. At the time of data cutoff, the last enrolled patient had been followed for approximately 6 months. Of 97 patients evaluable for efficacy analysis, 59 patients achieved tumor response, with a confirmed ORR of 61%, and all tumor responses were partial. The observed tumor responses were independent of age, sex, smoking history, EGFR exon 20ins isoform, brain metastases at baseline, prior lines of therapy, and history of tumor immunotherapy.

Summary: In this phase 2 study, suvotinib showed anti-tumor efficacy with a controllable safety profile in patients pretreated with platinum-based chemotherapy for EGFR exon 20ins non-small cell lung cancer.

The difference between pozitinib and suvotinib

1. Mechanism of action: Pozitinib is an irreversible pan-HER2 inhibitor. The small size and flexible structure of pozitinib enable it to enter restricted binding sites, overcome steric hindrance, and inhibit tyrosine kinase activity. Inhibition of tyrosine kinase activity prevents downstream effects of cell proliferation, leading to cell death.

Suvotinib can specifically bind to and inhibit the kinase activity of epidermal growth factor receptors with specific mutations, preventing the autophosphorylation and downstream signaling pathways of the receptor, thereby inhibiting the proliferation and growth of tumor cells.

2. Adverse reactions: Common adverse reactions of bochitinib are diarrhea, stomatitis, itching, paronychia, mucosal inflammation, rash, decreased appetite, hypokalemia and acneic dermatitis. Adverse reactions of suvotinib include rash, diarrhea, and oral ulcers.

Summary

There are certain differences between pocitinib and suvotinib in terms of their mechanism of action and adverse reactions. However, both are effective in treating non-small cell lung cancer. There is no conclusion that which one is better. It is recommended that patients choose medication based on their own conditions and under the advice of their doctor. They must not blindly use medication.

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