How effective is the targeted drug tepotinib in the treatment of non-small cell lung cancer?

The targeted drug Tepotinib has a significant effect in the treatment of non-small cell lung cancer. Studies have shown that Tepotinib can improve the objective response rate in the treatment of non-small cell lung cancer, prolong the life of patients, improve discomfort symptoms, and improve the quality of life of patients.

Tepotinib drug introduction

is a kinase inhibitor that targets mesenchymal-epithelial transition (MET) and is used to treat patients with metastatic non-small cell lung cancer who exhibit MET exon 14 skipping mutations. Tepotinib was first approved in Japan in March 2020 for the treatment of non-small cell lung cancer (NSCLC) with MET changes, and subsequently received accelerated approval from the US FDA in February 2021, under the trade name Tepmetko, for the treatment of adult patients with metastatic NSCLC and MET exon 14 skipping changes.

It is the first oral MET-targeted tyrosine kinase inhibitor that allows for once-daily dosing, an advantage that may help reduce the drug burden typically associated with chemotherapy regimens. In February 2022, tipotinib was approved for use in Europe.

Tepotinib in the treatment of non-small cell lung cancer

A study evaluated the antitumor activity and side effects of 500 mg of tepotinib taken orally once daily in patients with MET exon 14 skipping mutations until disease progression, withdrawal of consent, or adverse events leading to discontinuation.

From September 13, 2016, to January 1, 2020, a total of 6708 patients underwent pre-screening for MET alterations, and 169 patients were subsequently screened for MET exon 14 skipping mutations). Of these patients, 152 received tipotinib and 99 had at least 9 months of follow-up. The liquid biopsy group included 66 patients, and the tissue biopsy group included 60 patients. According to both methods, 27 patients obtained positive results.

1. Response rate and change from baseline in tumor burden:

According to independent review, among the 99 patients in the effective population, the objective response rate was 46%. All responses were one-sided, and no patient achieved complete remission. Response rates were consistent between the two biopsy groups: 48% in the liquid biopsy group and 50% in the tissue biopsy group. Response rates were similar regardless of baseline characteristics and number of prior lines of therapy.

According to the researcher's assessment, the response rate of the effective population was 56%. The researchers found that two patients achieved complete responses and 53 patients achieved partial responses, with response rates of 56% in the liquid biopsy group and 62% in the tissue biopsy group.

Tumor shrinkage was observed in most patients: 89% by independent review and 88% by investigator assessment. The response is rapid, usually within 6 weeks of starting treatment. The 146 patients who participated in the study had similar results, but the follow-up time was likely less than nine months.

2. Progression-free survival based on biopsy tissue data:

The median duration of response, independently reviewed, was 11.1 months in the combined biopsy group, 9.9 months in the liquid biopsy group, and 15.7 months in the tissue biopsy group. According to the investigators' assessment, the results were similar. According to an independent review, the median progression-free survival was 8.5 months in the combined biopsy group, 8.5 months in the liquid biopsy group, and 11.0 months in the combined biopsy group. The tissue biopsy groups were separated by 3 months, and the results were similar, according to the investigators' assessment.

As of the data cutoff, 27 of the 77 patients who had discontinued tipotinib had received subsequent treatment. Based on premature data, the median overall survival was 17.1 months.

3. Efficacy in patients with brain metastases: Among 11 patients with brain metastases (all non-target tumors [ie, not defined as target lesions according to RECIST]), the response rate by independent review was 55%, and the median response duration was 9.5 months. Among these patients, the median progression-free survival was 10.9 months.

Conclusions: The efficacy of tepotinib in the treatment of non-small cell lung cancer was significant, with the mean change in cough from baseline exceeding the predefined minimally important difference, indicating symptom reduction and stabilization of dyspnea and chest pain symptoms. Global functioning scores showed that patient-reported quality of life on the EORTC QLQ-C30 scale and EQ-5D-5L remained stable over time.

Safety of Tepotinib in the Treatment of Non-Small Cell Lung Cancer

Among the 152 patients in the safety population, 98% reported adverse events of any cause during treatment. Eighty-nine percent of patients reported adverse events that investigators considered related to tipotinib. Such events were grade 3 or higher in 28% of patients, with 25% grade 3 and 2% grade 4. The most common of these grade 3 or higher adverse events was peripheral edema.

Elevated amylase and lipase levels are common but mild to moderate in severity. This increase is asymptomatic and is not accompanied by symptoms of pancreatitis. For the most common adverse events of any grade, the median time to onset was 3 to 11 weeks after starting tipotinib, and for grade 3 or higher events, the interval was 10 to 27 weeks.

15% of patients reported serious adverse events thought to be related to tipotinib. Treatment-related adverse events resulted in dose reductions in 33% of patients and permanent discontinuation in 11% of patients. Such reductions or discontinuations were primarily related to peripheral edema, pleural effusion, or dyspnea.

Summary

Tepotinib has a significant effect in the treatment of non-small cell lung cancer and is a better choice. However, since tepotinib has some adverse reactions, it is recommended that patients pay attention to their own adverse reactions during treatment and strictly follow medical instructions to reduce the incidence of adverse reactions.

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