Patients with NSCLC and Brain Metastases at Baseline Derive Limited Benefit from Mobocertinib


The results, however, showed that remaining on mobocertinib may be warranted for patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer that has progressed after mobocertinib treatment.

The use of mobocertinib (Exkivity) demonstrated limited intercranial activity in patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer (NSCLC) with brain metastasis at presentation, according to study findings presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

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

“Patients with disease progression in the brain may derive overall benefit from ongoing mobocertinib treatment with combination [radiotherapy] to treat the brain lesions,” the authors wrote in their presentation.

This 3-part, open label, multicenter study (NCT02716116) comprised 114 patients [median age, 60 years; 66% female; 60% Asian) with an ECOG status 0 to 1 who had at least 1 or more prior lines of therapy for locally advanced/metastatic EGFR exon 20 insertion-positive NSCLC. At baseline, 35% of patients had brain metastases.

Patients received mobocertinib at 160 mg once daily 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.

Confirmed objective response rate (cORR) was 28% (n = 32;) and median duration of response (DOR) was 17.5 months in the overall platinum-pretreated cohort (n = 64). Additionally, cORR was 34% (n = 25) among previously treated patients with no baseline brain metastases, compared with 18% (n = 7) among those with baseline metastases; and progression free survival was 9.2 and 3.7 months, respectively.

Among patients in the platinum-pretreated cohort, 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 mobocertinib beyond disease progression and 19% continued treatment for at least 6 months. And out of 43 patients who had first site of disease progression that did not involve the brain, 65% continued treatment with mobocertinib — 9% for at least 6 months.

“These results suggest that mobocertinib may have limited intercranial activity given the high frequency of first PD in brain (25%) and numerically IRC-assessed cORR 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, 7 received brain radiotherapy and remained on mobocertinib (3 patients for 6 months or more and 1 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.


Jaane P, Ramalingam S, Yang J, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic non–small cell lung cancer (mNSCLC): treatment (tx) beyond progressive disease (PD) in platinum-pretreated patients (pts) with and without intracranial PD. J Clin Oncol. 2022; 40 (suppl_16):9099. doi: 10.1200/JCO.2022.40.16_suppl.9099

Related Videos
Common adverse effects following treatment with lenvatinib plus pembrolizumab in the phase 3 CLEAR study include diarrhea, hypertension, and fatigue, according to Thomas E. Hutson, DO, PharmD, FACP.
Lenvatinib in combination with pembrolizumab appears to raise no new safety signals in patients with advanced clear cell renal cell carcinoma after 4 years of follow-up in the phase 3 CLEAR study.
According to Thomas E. Hutson, DO, PharmD, FACP, 4-year follow-up data from the phase 3 CLEAR study confirm the maintained benefits of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Rana R. McKay, MD discusses presentations of interest that were presented at the 2023 Kidney Cancer Research Summit, including a discussion on how PET imaging may identify which patients with renal cell carcinoma may respond to immunotherapy.
A better understanding of tumor biology may be necessary for identifying novel non-immunotherapy–based therapeutic strategies for patients with renal cell carcinoma, according to Rana R. McKay, MD.
Probiotics and other agents targeting fatty acid oxidation are also under evaluation as treatment options for patients with renal cell carcinoma, according to Rana R. McKay, MD.
Other angiogenic agents are also under investigation in renal cell carcinoma, according to Rana McKay, MD, who indicates it will be interesting to see how they compare with belzutifan.
Expert on NSCLC
Related Content