Exkivity Delivers Minimal Benefit to Patients with Non-Small Cell Lung Cancer and Brain Metastases

Although ineffective in patients with non-small cell lung cancer and brain metastases at diagnosis, treatment with Exkivity may benefit patients with EGFR exon 20 insertion-positive metastatic disease.

For patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer (NSCLC) with brain metastases, the use of Exkivity (mobocertinib) was associated with limited intercranial (within the skull) activity, according to recent study results.

The data, however, indicated that patients who did not have brain metastases at trial enrollment, but whose disease progressed to the brain after initial Exkivity treatment derived a benefit from remaining on study therapy.

“Patients with disease progression in the brain may derive overall benefit from ongoing (Exkivity) treatment with combination (radiotherapy, RT) to treat the brain lesions,” the authors wrote in their presentation of the findings at the 2022 American Society of Clinical Oncology Annual Meeting.

This study included 114 patients (median age, 60 years; 66% female; 60% Asian) who had at least one or more prior lines of therapy for locally advanced/metastatic EGFR exon 20 insertion -positive NSCLC. At baseline, which is the start of the trial, 35% of patients had brain metastases.

Patients received Exkivity and were allowed to continue treatment beyond progressive disease at the discretion of the investigator if there was determined to be a clinical benefit. Additionally, patients with brain metastases were required to have the brain lesions treated and no symptoms of such prior to enrollment.

The confirmed objective response rate (or the rate of a measurable response to the treatment) among 32 patients was 28%. As for the median duration of response (the time the disease responds to a treatment without growth or spread), it was 17.5 months in the overall platinum-pretreated group (64 patients).

Additionally, confirmed objective response rate was 34% (25 patients) among previously treated patients with no baseline brain metastases, compared to 18% (7 patients) among those with; and progression-free survival (time during and after treatment when the patient lives without disease progression) was 9.2 and 3.7 months, respectively.

Among patients in the platinum-pretreated group, 21 (33%) had a first site of the disease involving the brain and 11 (17%) had first site of disease progression in the brain only. Of those 21 patients, 81% remained on Exkivity beyond disease progression and 19% continued treatment for at least six months. And out of 43 patients who had first site of disease progression that did not involve the brain, 65% continued treatment with Exkivity — 9% for at least six months.

“These results suggest that (Exkivity) may have limited intercranial activity given the high frequency of first (progressive disease) in brain (25%) and numerically IRC-assessed (confirmed objective response rate) in patients with baseline brain metastases,” the authors wrote in the abstract.

Of the 21 patients with first site of disease progression in the brain, seven received radiotherapy delivered to the brain and remained on Exkivity (three patients for six months or more and one patient for 12 months or more). Additionally, 12 patients remained on this treatment but did not receive radiotherapy.

“Optimal strategies for treating advanced EGFR exon-driven NSCLC with brain metastasis warrant continued investigation,” the authors concluded in their abstract.

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