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....

...- 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)....

...- The tumor harbored common EGFR mutations (Del19, L858R) at start of first-line treatment...

...- 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;...

...Uncommon EGFR mutations were defined as mutations in exon 18-21 but except for 19del, 21L858R and well-established drug resistant type (20 insertion, 20T790M, 19L747S, 19L747P, D761Y, 21T854A)....

...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....

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…

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)....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.

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.

This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations)....for patients with 21 Leu858Arg mutation, dacomitinib showed the most favorable overall survival, with the cumulative probabilities of 36.73%.

...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.

Dacomitinib showed a numerical improvement of OS relative to other EGFR TKIs: afatinib (hazard ratio [HR] 0.87; 95% credible interval [CrI]: 0.61–1.24), erlotinib (HR: 0.79; 95% CrI: 0.44–1.42), gefitinib (HR: 0.75; 95% CrI: 0.59–0.95) and osimertinib (HR: 0.94; 95% CrI: 0.68–1.29)...Dacomitinib should be considered as a first-line treatment option for patients diagnosed with advanced EGFR+ NSCLC.

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 common EGFR mutations, the median PFS was 14.6 months (95% CI 9.0–18.2) for dacomitinib and 9.6 months (95% CI 7.4–12.7) for erlotinib and the HR was 0.717 (95% CI 0.458–1.124) with two-sided log-rank, P = 0.146.