Poziotinib found to be valuable to treat mutated NSCLC

According to the findings presented at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies Virtual Congress 2021, individuals suffering from epidermal growth factor receptor (EGFR) exon 20 mutant metastatic non-small cell lung cancer (NSCLC) displayed clinically meaningful benefit following treatment with poziotinib (a potent, irreversible, tyrosine kinase inhibitor). Investigators presented the efficacy data from once daily poziotinib in treatment-naive individuals as well as exploratory data from twice-daily dosing.

The ZENITH20-3 trial incorporated 79 treatment-naïve subjects having metastatic NSCLC and EGFR exon 20 mutations who were treated with 16 mg once daily poziotinib. Participants were treated until death, disease advancement, or considerable toxicity. The ZENITH20-5 treated 40 subjects having NSCLC and EGFR or human epidermal growth factor receptor 2 (HER2) exon 20 mutations in randomized groups of poziotinib at 10, 12, 16 mg once daily or 6 and 8 mg twice daily.

The trial’s outcome parameters were:

1. Duration of response
2. Objective response rate (ORR per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) Progression-free-survival
3. Safety

Most of the patients in ZENITH20-3 demonstrated tumor reduction

In ZENITH20-3, the participants were followed for a median time of 9.2 months with 12/79 participants still remaining on therapy. According to the intent-to-treat analysis, an ORR of 27.8% (22/79) and a disease control rate of 86.1% was witnessed. In total, 91% of subjects were found to have tumor decline.

The median progression-free survival was 7.2 months and the median duration of response was 6.5 months. The adverse event profile was found to be comparable with the second-generation EGFR tyrosine kinase inhibitors with ≥ grade 3 rash in 33% of subjects and diarrhea in 23% of subjects.

ZENITH20-5 showed that twice-daily poziotinib dosing improved the adverse event profile.

Regarding the ZENITH20-5, the preliminary data from the randomized arms of once-daily versus twice-daily dosing (16mg once daily vs 8mg twice daily; 12mg once daily vs and 6mg twice daily) portrayed that the rates of expected adverse events were lower with twice-daily dosing in cycle 1.

Table 1: Rates of adverse events in patients

It was found that the twice-daily dosing schedules (8 mg and 6 mg) led to a relative decline in dose interruptions by 38% and 52% respectively. The updated tolerability, safety, and preliminary efficacy data will be presented.

Thus, poziotinib exerts clinically meaningful activity in metastatic NSCLC individuals having EGFR exon 20 mutations at 16 mg once a day dosing. Preliminary data of poziotinib in subjects with metastatic NSCLC and EGFR or HER2 exon 20 mutations indicated that the safety and tolerability profile can be improved by implementing a twice-daily dosing strategy and warrants further investigation.

You can also check the role of capmatinib , selpercatinib, and combination of erlotinib and ramucirumab to treat NSCLC.