VIZIMPRO is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.

The NCCN NSCLC Panel recommends dacomitinib as a first-line treatment option for patients with sensitizing EGFR-positive metastatic NSCLC based on these clinical trial data and the FDA approval….The most commonly described mutations in EGFR (exon 19 deletions, p.L858R point mutation in exon 21) are associated with responsiveness to EGFR tyrosine kinase inhibitor (TKI) therapy... EGFR EXON 19 DELETION OR L858R MUTATIONS….Progression on erlotinib (± ramucirumab or bevacizumab), afatinib, gefitinib, or dacomitinib….SUBSEQUENT THERAPY...Continue erlotinib (± ramucirumab or bevacizumab) or afatinib or gefitinib or dacomitinib (if T790M-).

Dacomitinib is the first second-generation TKI to improve PFS and OS over gefitinib in patients with dose reduction in both Del19 and L858R subgroups.

In a multinational, multicenter study, patients age 18 years or older (≥ 20 years in Japan and Korea) who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and newly diagnosed NSCLC with activating mutations in EGFR (exon 19 deletion or exon 21 L858R) were enrolled and randomly assigned in a 1:1 manner to dacomitinib (n = 227) or gefitinib (n = 225). Conclusion In patients with advanced NSCLC and EGFR activating mutations, dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (TKI) to show significant improvement in OS in a phase III randomized study compared with a standard-of-care TKI.

Pts with newly diagnosed stage IIIB/IV or recurrent NSCLC harboring an EGFR mutation (exon 19 del or exon 21 L858R ± exon 20 T790M) and without central nervous system metastasis were randomized….n pts with advanced EGFR mutation-positive NSCLC, daco is the first to show a significant improvement in OS in a phase 3 trial compared with a standard-of-care tyrosine kinase inhibitor.

In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation...Median duration of follow-up for progression-free survival was 22·1 months (95% CI 20·3-23·9). Median progression-free survival according to masked independent review was 14·7 months (95% CI 11·1-16·6) in the dacomitinib group and 9·2 months (9·1-11·0) in the gefitinib group (hazard ratio 0·59, 95% CI 0·47-0·74; p<0·0001).

...- The presence of an EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) in tumor specimen determined by the local laboratory....

...- The presence of an EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) in tumor specimen determined by the local laboratory;...

...Patients harboring uncommon EGFR mutations....

...- Presence of any EGFR-activating mutation (exon 19 deletion or exon 21 L858R substitution) or other uncommon EGFR mutations prior to anti-cancer treatment;...

...- Evidence of histo or cytopathology confirmed, advanced NSCLC (with known histology) with the presence of EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21)....

...Vizimpro® naïve patients to whom Vizimpro® can be prescribed as per the local labeling (the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations 2....

...- Biopsy proven recurrent or metastatic NSCLC (adenocarcinoma) with major EGFR mutation (exon 19 deletion or Leu858Arg mutation without the Thr790Met)...

For all patients, the mPFS was 15.3m(8/14), ORR was 78.6% while DCR was 100%.The iORR was 80% and iDCR was 100%. The mPFS in patients with 19Del (8/14,57.1%) and21L858R (6/14,42.9%) are 15.3 and 15.2m, ORR are 87.5% and 66.7%, respectively...Dacomitinib showed promising intracranial antitumor activity with a manageable safety profile as first-line therapy in EGFR-mutant NSCLC patients with multiple brain metastases.

This single-arm phase II study enrolled 30 patients with treatment-naïve advanced NSCLC harboring activating EGFR mutations from January 2021 to June 2021 and started them on dacomitinib (45 mg/day)….Patients had exon 19 deletions (46.7%) and L858R mutations in exon 21 (55.3%). The confirmed iORR was 96.7% (29/30), with an intracranial complete response of 63.3%....Dacomitinib has outstanding intracranial efficacy in patients with EGFR-mutant NSCLC with brain metastases.

ATORG-003 (9 sites, 5 Asian countries) is enrolling newly diagnosed stage IIIB-IV NSCLC pts with EGFR mutations (exon 19 deletion [ex19del] or L858R). Pts receive dacomitinib 30 mg orally once daily….The iORR was 67% (1 intracranial CR [iCR], 5 intracranial PR), and median intracranial duration of response (iDoR) was not reached (NR). In 14 pts with non-measurable CNS mets only, iCR was seen in 6 (43%) pts. Median iPFS was NR with only n=5 CNS progression events in the entire cohort and n=7 remain on treatment. Overall (intra and extracranial) ORR was 67% and PFS rate at 12 mo was 42%.....Dacomitinib has significant intracranial activity with observed durable responses in advanced EGFR mutated NSCLC with CNS mets.

In this retrospective study, 21 enrolled patients who had progressed on previous EGFR-TKI and chemotherapy were treated with dacomitinib 45 mg or 30 mg orally daily until disease progression or intolerability....Three patients with an original sensitizing EGFR L858R mutation and one patient with exon 19 deletion had partial responses…

Among 49 evaluable patients, 26.5% (13 patients) had a confirmed partial response and 73.5% (36 patients) had disease control...the median progression-free survival was 5.4 months (95% CI, 3.5–7.3 months), and the half-year, 1-year, and 2-year OS rate were 79.2%, 70.6%, and 64.1%, respectively....As to mutation types, the ORRs of 19del, 21L858R, and rare mutations were 28.6%, 12.5%, and 54.5%, respectively (Figure S1D)...different mutation subtypes demonstrated different PFS (mPFS, 10.3 vs. 6.4 vs. 3.8; p = 0.351) (Figure 2G) and OS (1-year OS rate, 90.0% vs. 79.0% vs. 60.9%; p = 0.288) (Figure 2H), with rare mutations (n = 11) demonstrating better treatment responses and prognosis, followed by 19del (n = 15) and 21L858R (n = 30)....This real-world study has shown that dacomitinib is active and well-tolerated in NSCLC patients harboring different EGFR mutations in later-line settings, even for those with brain metastases.

...single center retrospective study of EGFR mutated advanced NSCLC patients treated with dacomitinib…Type of mutations was Del 19 in 27 pts, L858R in 12 pts, G719X in 2pts, and Del 19 + L858R, L861Q in one patient each....38 pts have evaluable response: complete response in 2, partial response in 34 and stable disease in 2 pts....Response rate was high and durable.

This real-world cohort study with 14 patients has shown for the first time that dacomitinib have potent efficacy for CNS metastasis in both L858R and 19del EGFR-positive patients with NSCLC.

In total, 14 of 59 EGFR-mutant advanced NSCLC patients who received first-line dacomitinib therapy had brain metastasis before treatment….Eight patients harbored EGFR 19del, 5 had EGFR L858R, and one patient had EGFR G719A and I706 T co-mutations….The ORR was 92.9 % (13/14) and the disease control rate (DCR) was 100 %.

...the presence of exon 19 deletion and exon 21 L858R mutations in each trial ranged from 43 to 65% and 35 to 57%, respectively....Dacomitinib demonstrated a trend toward improved PFS and therefore, should be considered one of the standard first-line therapies for Japanese patients diagnosed with EGFR+ non-small-cell lung cancer.

Among subgroups, dacomitinib showed a numerical improvement of OS compared with all other EGFR TKIs among patients with exon 21 L858R substitution mutation and among Asian patients while osimertinib showed a numerical improvement of OS compared with all other EGFR TKIs among patients with exon 19 deletion mutation and among non-Asian patients.

The intracranial ORR and DCR among 5 response- evaluable patients with at least one follow-up disease assessment were 40% and 100% (2/5 complete response, 3/5 stable disease)….dacomitinib may have CNS efficacy in patients with untreated EGFR+ NSCLC in the real-world setting.

...patients with EGFR-activating mutation-positive (EGFR-positive; exon 19 deletion or exon 21 L858R substitution mutations)...In 81 Japanese patients (40 dacomitinib, 41 gefitinib), PFS was longer with dacomitinib compared with gefitinib…Our results confirm the efficacy and safety of first-line dacomitinib in Japanese patients with EGFR-positive advanced NSCLC.

For patients with exon 19 mutations, the estimate of median PFS was 14.6 months (95% CI 9.2–20.6) with dacomitinib and 10.0 months (95% CI 7.2–12.8) with erlotinib. The HR for PFS favored dacomitinib with a HR of 0.585 (95% CI 0.335–1.024, two-sided log-rank, P = 0.058)