Pfizer's Vizimpro (Dacomitinib) Recommended by NICE for First-Line Treatment of EGFR-Mutated NSCLC in the UK

Compiled by: Fan Dongdong

Pfizer’s Vizimpro (dacomitinib) Recommended in the UK as First-Line Treatment for Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)Recently, Pfizer’s Vizimpro (dacomitinib) received a positive recommendation from regulatory authorities in the UK as a first-line treatment option for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The latest guidelines issued by the National Institute for Health and Care Excellence (NICE) indicate that the UK National Health Service (NHS) will provide access to this therapy for adult patients with epidermal growth factor receptor (EGFR) mutation-positive NSCLC.

Vizimpro is an oral, once-daily pan-human epidermal growth factor receptor (pan-EGFR) tyrosine kinase inhibitor (TKI). In the United States, Vizimpro was approved in late September 2018 for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) confirmed to have EGFR exon 19 deletions or exon 21 L858R substitution mutations. This April, the drug received marketing approval from the European Commission. Additionally, Vizimpro has also been approved by Japanese regulatory authorities for the treatment of patients with unresectable or recurrent NSCLC harboring EGFR mutation-positive tumors.

EGFR is a protein that facilitates cell growth and division. Mutations in the EGFR gene lead to protein overactivation, thereby promoting the development of cancer cells. EGFR gene mutations are present in 10%–35% of patients with non-small cell lung cancer (NSCLC). The most common activating mutations are exon 19 deletions and the exon 21 L858R substitution, which account for 80% of known activating EGFR mutations.

Previously, NICE had refused to include the drug in the UK’s National Health Service (NHS) reimbursement system, deeming this tyrosine kinase inhibitor not cost-effective.

Vizimpro is priced at £2,703 per pack of 30 capsules in the UK, but the company has provided a confidential discount to the NHS. Evidently, the NHS is satisfied with the final confidential price. Meindert Boysen, Director of the Centre for Health Technology Evaluation at NICE, stated that the committee considered “Vizimpro more likely to extend life in patients with this type of lung cancer compared to existing NHS treatments. The pricing offered by Pfizer led the committee to reconsider its decision on the drug.”

The approval of Vizimpro was based on data from the Phase III clinical study ARCHER 1050. This study was a randomized, open-label, head-to-head trial conducted in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. It evaluated the efficacy and safety of Vizimpro compared with AstraZeneca’s first-generation EGFR-targeted drug Iressa as first-line treatment, with progression-free survival (PFS) as the primary endpoint.

Research data showed that, compared with the Iressa treatment group, the Vizimpro treatment group achieved a statistically significant and clinically meaningful prolongation of PFS (14.7 months vs. 9.2 months), with a 41% significant reduction in the risk of death or disease progression, thereby meeting the primary endpoint of the study.

Overall survival (OS) data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting last June showed that the median OS in the Vizimpro treatment group was 34.1 months, representing a 7-month extension compared to the Iressa treatment group. At 30 months of treatment, the survival rate was 56.2% in the Vizimpro group versus 46.3% in the Iressa group.

In terms of safety, the most common adverse reactions in the Vizimpro treatment group included diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, weight loss, alopecia, cough, and pruritus. Serious adverse reactions occurred in 27% of patients in the Vizimpro treatment group, with the most common being diarrhea and interstitial lung disease.

Some have pointed out that Vizimpro has a higher incidence of side effects. To avoid the occurrence of severe adverse reactions, it may be necessary to choose a lower dose when taking the medication. Currently, Pfizer has developed three targeted drugs for the treatment of three different types of mutation-driven lung cancer:

• The first-generation ALK inhibitor Xalkori (crizotinib) is used for the treatment of ALK-positive or ROS1-positive NSCLC;

• Vizimpro, a second-generation EGFR inhibitor, is used for the treatment of EGFR-mutant NSCLC;

• Third-Generation ALK Inhibitor Lorbrena for the Treatment of ALK-Positive NSCLC

References:

1、NICE OK for life-extending Vizimpro in lung cancer

2、NICE clears front-line NHS use for Pfizer’s lung cancer drug Vizimpro

3、Vizimpro recommended on NHS for NSCLC-NICE