FDA Approves Vizimpro for EGFR-Positive Lung Cancer

September 28, 2018

The Food and Drug Administration (FDA) has approved Vizimpro (dacomitinib) for the frontline treatment of patients with metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations, according to Pfizer, the manufacturer of the pan-human EGFR tyrosine kinase inhibitor (TKI).

The Food and Drug Administration (FDA) has approved Vizimpro (dacomitinib) for the frontline treatment of patients with metastatic non—small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations, according to Pfizer, the manufacturer of the pan-human EGFR tyrosine kinase inhibitor (TKI).

The approval is based on the phase 3 ARCHER 1050 trial, in which Vizimpro reduced the risk of disease progression or death by more than 40 percent and resulted in an average 6.5-month improvement in response duration compared with Iressa (gefitinib) as a first-line treatment for patients with advanced, EGFR-positive NSCLC.

The median progression-free survival (PFS) for patients who received Vizimpro was 14.7 months compared with 9.2 months for participants who received Iressa. The median duration of response (DOR) was 14.8 months with Vizimpro versus 8.3 months with Iressa.

Data presented at the 2018 ASCO Annual Meeting also showed that at a median follow-up of 31.1 months, the median overall survival was 34.1 months in patients randomized to Vizimpro versus 26.8 months in those randomized to Iressa.2

EGFR-mutated advanced non—small cell lung cancer is a common illness, especially in the Asian population, and new treatment options will ultimately benefit patients,” Professor Tony Mok, M.D., primary investigator for the ARCHER 1050 study and Chair of Department of Clinical Oncology, The Chinese University of Hong Kong, said in a statement. “The findings from ARCHER 1050 suggest that Vizimpro should be considered as a new first-line treatment option for patients with EGFR-mutated non—small cell lung cancer exon 19 deletion or exon 21 L858R substitution mutations.”

ARCHER 1050 was designed with a primary endpoint of PFS as assessed by blinded independent review, with DOR, overall response rate (ORR), and safety as secondary endpoints. The trial recruited patients with newly diagnosed stage 3B/4, EGFR-positive NSCLC who had not received prior systemic therapy including TKIs and an ECOG performance status of 0 or 1. Patients also could not have any metastases in the central nervous system (CNS).

A total of 452 patients were randomized in a 1 to 1 ratio to either receive 45 mg daily of Vizimpro (227 patients) or 250 mg daily of Iressa (225 patients). Baseline patient characteristics were balanced across the two arms of the study, including in terms of race and smoking status. In the Vizimpro arm, about 75 percent of participants were Asian and nearly 65 percent were never-smokers. In the Iressa arm, 78 percent were Asian and 64 percent were never-smokers. The median age was 61 to 62 years.

Although PFS was similar in both arms at the six-month mark, the difference in PFS became very apparent by the 24-month mark. At 24 months, 30.6 percent of patients in the Vizimpro arm were progression free, compared with 9.6 percent in the Iressa group. However, there was not a statistically significant difference in ORR, with 74.9 percent of patients in the Vizimpro achieving a response versus 71.6 percent of patients in the Iressa arm. Overall survival data were not yet mature at the time of the analysis.

The data cut-off for the OS analysis was February 17, 2017, with 220 (48.7 percent) deaths observed at that time. The OS probability at 30 months was 56.2 percent in the Vizimpro arm and 46.3 percent in the Iressa arm. One patient randomized to Vizimpro and 11 randomized to Iressa had CNS metastases at progression.

OS subgroup analyses were consistent with the primary OS analysis across most baseline characteristics. Patients with exon 19 deletion had a median OS of 34.1 months with Vizimpro versus not reached with Iressa. Those with exon 21 L858R mutation had a median OS of 32.5 months in the Vizimpro arm compared with 23 months in the Iressa.

In terms of adverse events (AEs), there was more toxicity observed in the Vizimpro arm than in the Iressa arm. Gastrointestinal all-grade AEs were more common in the Vizimpro arm compared with the Iressa arm, including diarrhea (87.2 percent vs 55.8 percent, respectively) and decreased appetite (30.8 percent vs 24.6 percent). More patients in the Vizimpro arm compared with the Iressa arm also experienced paronychia (nail infection) (61.7 percent vs 20.1 percent), dermatitis acneiform (48.9 percent vs 28.6 percent) and stomatitis (43.6 percent vs 17.9 percent). However, increases in ALT levels were observed more in the Iressa arm (39.3 percent) compared with the Vizimpro arm (19.4 percent).

The most frequent grade 3 AEs in the Vizimpro arm were rash (14 percent) and diarrhea (8 percent). Two percent of patients receiving Vizimpro had grade 4 AEs. There were two grade 5 AEs, diarrhea and liver disease. Discontinuation due to treatment-related AEs occurred in 10 percent versus 7 percent of the Vizimpro versus Iressa arms, respectively.


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