Dramatic Response of Brain Metastasis from &lt;i&gt;EGFR&lt;/i&gt;-mutation-positive NSCLC to Dacomitinib

Kudo, Kenichiro; Kawakado, Keita; Kawajiri, Tomoka; Nishi, Tatsuya; Makimoto, Go; Tamura, Tomoki; Kuyama, Shoichi; Tanimoto, Mitsune

doi:10.2169/internalmedicine.4449-20

Cited by 8 publications

(4 citation statements)

References 6 publications

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“…Although the ARCHER 1050 study excluded patients with brain metastasis, subgroup analysis revealed that brain metastases developed as the site of progression in only one patient in the dacomitinib arm as compared with 11 patients in the gefitinib arm, suggesting that dacomitinib may prevent or delay the development of brain metastasis. A case report confirmed the efficacy of dacomitinib for brain metastatic lesions in an elderly patient with an EGFR mutation who had failed on previous lines of TKI treatment and chemotherapy [4]. Due to the limited number of patients in studies reported thus far, this investigation included patients with treatment-naive NSCLC and brain metastases to evaluate the intracranial activity of dacomitinib.…”

Section: Introductionmentioning

confidence: 71%

Dacomitinib induces objective responses in metastatic brain lesions of patients with EGFR-mutant non-small-cell lung cancer: A brief report

Peng

Jiang

et al. 2021

Lung Cancer

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Dacomitinib is a potent, irreversible and pan-HER tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Currently, evidence of its activity on brain metastasis is lacking. Materials and methods: NSCLC patients diagnosed at Hunan Cancer Hospital between July, 2019 and July, 2020 with enhanced MRI-detected brain metastasis prior to treatment and laboratory-confirmed EGFR mutations were reviewed. In total, 14 EGFR-mutant NSCLC patients with brain metastasis were treated with first-line dacomitinib. The first radiographic review of chest CT and brain MRI was after one month and thereafter every 2 months. The objective response rate (ORR) and the depth of the brain metastasis response were determined via RECIST 1.1 and RANO-LM criteria. Results: In total, 14 of 59 EGFR-mutant advanced NSCLC patients who received first-line dacomitinib therapy had brain metastasis before treatment. Among these patients, 5 were given a dacomitinib starting dose of 45 mg once daily, while 9 received 30 mg daily until disease progression or unbearable toxicity. Eight patients harbored EGFR 19del, 5 had EGFR L858R, and one patient had EGFR G719A and I706 T co-mutations. The median duration of follow-up was 4.5 months. All patients received at least one review. The ORR was 92.9 % (13/14) and the disease control rate (DCR) was 100 %. A measurable response of the intracranial metastases was observed in 12 of 14 patients (85.7 %), including 12 of 13 (92.3 %) with brain parenchymal metastasis, but the one patient with meningeal metastasis did not respond well. All patients (100 %) had grade 1-2 adverse effects, but none discontinued treatment or required a dosage adjustment. Conclusions: This case series study of 14 patients has shown that dacomitinib has potent efficacy for central nervous system (CNS) metastasis in EGFR-positive NSCLC. More data are required to confirm its advantages and optimize its clinical application.

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Section: Introductionmentioning

confidence: 71%

Dacomitinib induces objective responses in metastatic brain lesions of patients with EGFR-mutant non-small-cell lung cancer: A brief report

Peng

Jiang

et al. 2021

Lung Cancer

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“…There are only two case reports on dacomitinib therapy for cases previously treated for brain metastases, and they indicated successful treatment with dacomitinib for patients with brain metastases who failed previous EGFR-TKIs. 32,33 Although the treatment induction lines for dacomitinib are different, dacomitinib might be effective against brain metastases.…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of dacomitinib in rechallenge setting for patients with epidermal growth factor receptor mutant non–small cell lung cancer: A multicenter retrospective analysis (TOPGAN2020‐02)

et al. 2022

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Background Dacomitinib is the second‐generation epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor (TKI) for mutant non–small cell lung cancer (NSCLC). EGFR‐TKIs are often re‐administered in Japan after the disease progression prior EGFR‐TKI. There is little evidence of dacomitinib in rechallenge setting. This study evaluated clinical outcomes of dacomitinib in rechallenge setting. Methods Patients who received dacomitinib for advanced EGFR‐mutant NSCLC who had progressed after EGFR‐TKI in nine institutions in Japan were included in the analyses. Results In total, 43 patients were analyzed. The median progression‐free survival (PFS) was 4.3 months (95% confidence interval [CI], 2.5–5.6). The overall survival (OS) was 10.5 months (95% CI, 7.4–not reached). The overall response rate was 25.5% (95% CI, 13.1–33.7). Subset analysis indicated that patients with EGFR exon 21 L858R showed longer PFS than those with EGFR exon 19 deletion (5.8 vs. 4.1 months) (p = 0.018). The most common adverse events leading to dose modification were diarrhea, paronychia, rash, and oral mucositis. Conclusion In the real practice in Japan, dacomitinib showed a worthwhile treatment option for NSCLC patients with EGFR mutation after failure of previous EGFR‐TKI. The benefit was especially pronounced in patients with the exon 21 mutation.

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“…Ma et al reported that afatinib and osimertinib were effective in four of seven patients with uncommon EGFR mutations found in cerebrospinal fluid ctDNA [ 29 ]. KCSG-LU15-09 study reported that patients with uncommon EGFR mutations taking osimertinib 80 mg orally once per day could achieve an intracranial ORR of 40.0% (2/5) [ 25 ].Several studies have demonstrated the potential efficacy of dacomitinib in EGFR -positive NSCLC with CNS metastases, with ORR ranging from 87.5% to 92.9% and DCR of 100% [ 30 – 33 ]. A recent study by Li et al showed that intracranial disease control was observed in 92.9% of advanced NSCLC patients with brain metastasis treated with dacomitinib (13/14) [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutation: an ambispective cohort study

Pu,

Zhou,

Kong

et al. 2023

BMC Cancer

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Background About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC. Methods Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Result Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32–23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs. Conclusions Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.

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Dramatic Response of Brain Metastasis from <i>EGFR</i>-mutation-positive NSCLC to Dacomitinib

Cited by 8 publications

References 6 publications

Dacomitinib induces objective responses in metastatic brain lesions of patients with EGFR-mutant non-small-cell lung cancer: A brief report

Dacomitinib induces objective responses in metastatic brain lesions of patients with EGFR-mutant non-small-cell lung cancer: A brief report

Clinical efficacy of dacomitinib in rechallenge setting for patients with epidermal growth factor receptor mutant non–small cell lung cancer: A multicenter retrospective analysis (TOPGAN2020‐02)

Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutation: an ambispective cohort study

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