Dacomitinib monotherapy significantly prolonged progression-free survival in Asian patients with locally advanced or metastatic non–small cell lung cancer with epidermal growth factor receptor-activating mutations, according to results of a subgroup analysis from the phase III ARCHER 1050 study, Pfizer reported in a press release.
Tony S.K. Mok, MD, FRCPC, FASCO
Dacomitinib monotherapy significantly prolonged progression-free survival (PFS) in Asian patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations, according to results of a subgroup analysis from the phase III ARCHER 1050 study (NCT01774721), Pfizer reported in a press release.1The results were presented by Tony S.K. Mok, MD, FRCPC, FASCO during the 2019 European Society for Medical Oncology (ESMO) Asia Congress.
For the 346 patients involved in the subgroup analysis, first-line treatment with dacomitinib resulted in a PFS of 16.5 months compared with gefitinib (Iressa), which had a 9.3-month PFS (HR, 0.509; 95% CI, 0.391-0.662;P<0.0001). An extended follow-up also showed that dacomitinib improved overall survival in study subjects. The median OS was 37.7 months compared with 29.1 months in the gefitinib arm, (HR, 0.759; 95% CI; 0.578-0.996).
The duration of response (DoR) for patients who received dacomitinib was also longer than the DoR seen in patients who received gefitinib, 16.6 months versus 8.3 months, respectively.
The most common adverse events (AEs) witnessed in the Asian subgroup patients who were treated with dacomitinib were, diarrhea (90.6%), paronychia (64.7%), and dermatitis acneiform (56.5%). These AEs resulted in similar rates of dose reduction and treatment interruptions in both the subgroup population and the as-treated population. Between the two groups, there were no clinically relevant differences in AE frequency.
“We reported, in both the intent-to-treat population as well as the Asian subgroup, that OS benefit was maintained in patients who had a dose modification with dacomitinib at 30mg or 15mg QD. This is important as dose modification is the most effective way to manage toxicity, thereby enabling therapy to be better tolerated without compromising on efficacy of treatment," said Mok, professor, Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China, in a statement.
In the study, 452 patients were randomized 1:1 to either 45 mg dacomitinib tablets given orally daily or 250 mg gefitinib tablets, which were also administered orally, every day. The study evaluated the efficacy and safety of dacomitinib monotherapy with PFS based on the Independent Radiologic Central (IRC) Review as the primary endpoint. The key secondary endpoints were investigator-assessed PFS, the number of participants with the best overall response based on IRC and investigator assessment, objective response rate, DoR, and the number of participants with treatment-emergent adverse events and serious adverse events.
The inclusion criteria required participants to have histo or cytopathology confirmed, advanced NSCLC with a presentEGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21). Patients were permitted to join the study if they also had an exon 20 T790M mutation. Other eligibility requirements included having a minimum of 12 months disease-free interval between completion of systemic therapy and NSCLC recurrence, and Eastern Cooperative Oncology Group performance score of 0 to 1, and satisfactory renal, hematologic, and liver function.
Showing evidence of mixed histology that includes elements of small cell or carcinoid lung cancer, in addition to having another mutation, history of brain or leptomeningeal metastasis, uncontrolled medical conditions, and previous anti-cancer systemic treatment of early, locally advanced, or metastatic NSCLC resulted in exclusion from the ARCHER 1050 trial.
In September of 2018,dacomitinib received FDA approval for the first-line treatment ofEGFR-positiveNSCLC based on earlier findings from the ARCHER 1050 trial. The findings were presented during the 2018 ASCO Annual Meeting and showed an OS of 34.1 months in the dacomitinib group versus 26.8 in the gefitinib group. The PFS at that time was 14.7 months compared with 9.2 months, respectively. The same findings also led to approval from the European Medicines Agency.
Pfizer reported that dacomitinib is undergoing further development across multiple sites through a partnership with SJF Pharmaceuticals, which began in 2012.
The phase III ARCHER 1050 study is no longer enrolling patients, but the study remains active with a target completion date of December 31, 2020.
Pfizer Unveils Positive Results from Asian Subgroup Analysis of ARCHER 1050 [press release]. Singapore, Malaysia: Pfizer. November 25, 2019. https://yhoo.it/2DerY56. Accessed November 25, 2019.