medwireNews: The selective EGFR–tyrosine kinase inhibitor (TKI) poziotinib has clinical activity in previously treated non-small-cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertions, suggest phase 2 study data presented at the 2020 AACR Virtual Annual Meeting I.
Presenting author Xiuning Le (The University of Texas MD Anderson Cancer Center, Houston, USA) noted however that the primary endpoint of the trial was not met, and the discussant described the safety profile of poziotinib as “a challenge.”
But Le also highlighted the lack of approved therapies for this patient population, who do not respond to other available EGFR–TKIs, making this a population of “unmet medical need.”
Therefore, in light of the clinical activity of poziotinib observed in the ZENITH20 trial, the researchers plan to continue enrolment and investigate alternative dosing regimens to improve tolerability.
The multicenter trial included 115 patients (67% women) with a median age of 61 years who had received a median of two prior lines of therapy.
Treatment with poziotinib 16 mg daily led to an objective response rate ORR of 14.8%, where the lower limit of the 95% confidence interval fell below the prespecified cutoff of 17% and thus the trial’s primary endpoint was not met, reported Le.
Discussant Taofeek Owonikoko (Emory University, Atlanta, Georgia, USA) emphasized that the response rate is “significantly less” than the ORR of 38% observed in a prior single-center study of the agent.
Nevertheless, the majority (65.0%) of trial participants experienced a reduction in tumor size, the disease control rate was 68.7%, and responses lasted for a median of 7.4 months, which Owonikoko described as a “respectable” duration. The median progression-free survival was 4.2 months.
Furthermore, Le noted that “the response rate was maintained across lines of therapy,” in subgroup analyses and a benefit was observed even in heavily pretreated patients who had three or more lines of therapy, including those who had received previous EGFR–TKI therapy.
In terms of the safety profile, 63% of patients experienced a grade 3–4 treatment-related adverse event (TRAE), most commonly rash (29%) and diarrhea (26%). Consequently 10% of the study participants permanently discontinued treatment and 68% required a dose reduction.
Le concluded that the trial is ongoing with three new cohorts and dosing adjustments that include a lower daily dose and twice a day dosing.
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