Real-World Efficacy Greater Than Trial Data For Dacomitinib in EGFR+ NSCLC

The survival benefit of dacomitinib was improved in real-world settings for patients with EGFR-mutant NSCLC compared with what the ARCHER 1050 trial shows.

Dacomitinib (Vizimpro) improved survival in the first-line treatment of patients with non–small cell lung cancer (NSCLC) harboring common EGFR mutations in real-world settings, according to a study published in Scientific Reports.¹

With a median follow-up of 16.9 months (range, 5.9-27.9), the median progression-free survival (PFS) was 16.7 months (95% CI, 14.4-25.2). Sorted by type of EGFR mutations, those with exon 19 deletion experienced a median PFS of 18.1 months (95% CI, 14.5-not reached [NR]) vs 15.9 months (95% CI, 12.5-NR) in those with L858R mutations. The median overall survival (OS) was NR, and the 24-month OS rate was 83.9%. In patients with brain metastasis, the median PFS was 14.5 months (95% CI, 11.2-20.0) vs 20.2 months (95% CI, 17.5-NR) in those without (P = .037).

The overall response rate (ORR) was 84.3%; 1 patient (0.7%) achieved a complete response, 128 (83.7%) achieved partial responses, 11 (7.2%) had stable disease, 6 (3.9%) had progressive disease, and 7 (4.6%) had unknown outcomes. The disease control rate was 91.5%.

“For the overall population, ORR was 84.3% and the median PFS was 16.7 months, which was quite superior to the survival results represented in [the ARCHER 1050 trial (NCT01774721)],” senior study author Byoung Yong Shim, from the Department of Internal Medicine, Division of Medical Oncology, College of Medicine at St. Vincent’s Hospital, South Korea, and coauthors wrote in the study.^1,2 “With a tolerable safety profile and superior survival efficacy compared with previous prospective studies, [dacomitinib] is anticipated to be a valuable second-generation EGFR tyrosine kinase inhibitor [TKI] in clinical practice. Additionally, the study highlights its efficacy in patients with brain metastasis, establishing it as one of the viable treatment options for [patients with] NSCLC with brain metastasis.”

Between January 6th, 2021, and December 9th, 2022, a total of 153 patients were administered dacomitinib in a real-world, first-line setting at Samsung Medical Center and St. Vincent’s Hospital in South Korea. The median age of patients at diagnosis was 64.6 years (range, 54.5-74.7), 60.8% were female, 65.4% had an ECOG performance status of 1, and 68.6% never smoked. The majority of patients had adenocarcinoma (96.1%), stage IV disease at diagnosis (64.7%), and previous curative surgery (30.7%). Additionally, 50.3% had exon 19 deletion type mutations, 46.4% had L858R type mutations, and 3.3% had other types of mutations. Regarding distant metastasis at dacomitinib initiation, 45.1% had brain metastasis, 36.6% had bone, 29.4% had pleura, 6.5% had liver, and 4.6% had adrenal gland.

Eligible patients had advanced or metastatic NSCLC with an EGFR mutation and received first-line dacomitinib between the trial date range at either of the 2 participating centers.

Dacomitinib was given at 45 mg once daily in 28-day cycles until either objective disease progression, unacceptable toxicity, or death; when patients experienced treatment-related toxicities of grade 2 or higher, they transitioned to 30 mg per day or 15 mg per day.

Trial end points were ORR, PFS, OS, safety, and subsequent treatments after progression on dacomitinib.

Of the 66 patients who progressed while on dacomitinib, 22 of them remained on dacomitinib through the concept of beyond progression; lesions associated with progression in the brain, bone, and lung occurred in 11, 9, and 3 patients, respectively.

To confirm the acquired resistance mechanism of dacomitinib, 31 patients underwent tissue re-biopsy, and 25 underwent liquid biopsy; of those 56 patients, 27 had the EGFR T790M mutation in exon 20. All these patients, except for 1, switched to either osimertinib (Tagrisso; n = 11) or lazertinib (Lazcluze; n = 15). Of the 29 patients who didn’t have the T790M mutation, 16 received platinum-based cytotoxic chemotherapy, 3 were enrolled in a clinical trial, and others refused treatment due to poor performance status or were transferred to another hospital.

Regarding safety, 94.1% of patients experienced at least one adverse event (AE), with 7.2% experiencing AEs of grade 3 or higher. The most common AEs of any grade were rash (51.0%), diarrhea (49.0%), oral mucositis (40.5%), paronychia (39.2%), and dermatitis (29.4%).

AEs led to dose reduction in 85.6% of patients, with 49.0% going to 30 mg per day and 36.6% going to 15 mg per day. Toxicity led to temporary interruption in 24.2% of patients and permanent discontinuation in 8.5%.

References

1. Shin JE, Jung HA, Park S, et al. Real-world data of dacomitinib as first-line treatment for patients with EGFR-mutant non-small-cell lung cancer. Sci Rep. 2025;15:4593. doi:10.1038/s41598-024-81704-4
2. ARCHER1050: A study of dacomitinib vs. gefitinib in 1st-line treatment of advanced NSCLC. ClinicalTrials.gov. Updated November 14, 2023. Accessed February 24, 2025. https://tinyurl.com/3j4rbdye