Results from the phase III ARCHER 1050 trial presented at the 2018 ASCO Annual Meeting showed that the second-generation EGFR tyrosine kinase inhibitor (TKI) dacomitinib improved overall survival (OS) compared with a standard first-generation TKI in patients with
-mutant non–small cell lung cancer (NSCLC).
During a median follow-up time of 31.3 months, the OS probability for patients treated with dacomitinib was 56.2% versus 46.3% for those who received gefitinib. In the phase III trial, patients were randomized to orally receive either 45 mg/day of dacomitinib or 250 mg/day of gefitinib.
Earlier data from ARCHER 1050 that were presented at the 2017 ASCO Annual Meeting showed that dacomitinib reduced the risk of disease progression or death by more than 40% and resulted in an average 6.5-month improvement in response duration compared with gefitinib.2
Regarding toxicity in the OS analysis, rates of grade ≥3 diarrhea (8.8% vs 0.0%), paronychia (7.5% vs 1.3%), dermatitis acneiform (13.7% vs 0%), and stomatitis (3.5% vs 0.4%) were higher in dacomitinib-treated patients. Moreover, two-thirds of patients who received dacomitinib required dose reductions.
Based on the progression-free survival (PFS) data, the FDA granted a priority review designation to the investigational second-generation EGFR inhibitor in April 2018 for the frontline treatment of patients with EGFR
-mutant NSCLC. Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision by September 2018.
In an interview with OncLive
during the 2018 ASCO Annual Meeting, Mok, professor, Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China, discussed the promise of dacomitinib for the frontline treatment of patients with EGFR
OncLive: Can you provide some background on the ARCHER 1050 study?
: ARCHER 1050 is a randomized phase III trial that compared dacomitinib with gefitinib. Dacomitinib is a second-generation EGFR
TKI, meaning that it actually has a pan-HER inhibition as well as covalent bonding with the EGFR
mutations. In other words, it is supposed to be a more potent EGFR
inhibitor. The big question here was, “Will a second-generation [inhibitor] be more potent than the standard first-generation [inhibitor]? That was the rationale behind ARCHER 1050. We presented the outcomes for PFS last year.
What were some of the updated data presented this year?
This year, after a median follow-up time of about 31 months, we were able to achieve the OS outcome. In total, we had 220 deaths, and with that, we were able to demonstrate a significant improvement in OS. The median OS was 34.1 months [for dacomitinib] versus about 27 months [for gefitinib]. This will become the first randomized phase III study comparing two TKIs with the demonstration of improvement of OS.
What is the key takeaway from this research?
The key message of ARCHER 1050 is that with the more potent EGFR inhibition, we were able to achieve improvements in both PFS and OS. Therefore, this is a very important scientific message. Also, it allows the market to have one extra option in the first-line situation, to be able to choose dacomitinib for first-line management.
Is there anything else that you would like to highlight from this study?
The one area we did not touch on yet is toxicity. With more potent inhibition, that means there will be more so-called EGFR inhibition side effects. That means [there is] diarrhea, mucositis, and skin rashes. We did observe more significance in toxicity. As a result, we required a reduction in two-thirds of patients. Overall, we have to adjust and monitor the toxicity carefully while we use this drug.
Looking at the 2018 ASCO Annual Meeting overall, were there any other abstracts presented that excited you?
I am most excited about another study I led, which is KEYNOTE-042. This tested the use of single-agent pembrolizumab versus the standard chemotherapy in patients with a PD-L1 expression over 1%. This was a randomized phase III study that used OS as a primary endpoint. We had 3 different cutoffs for PD-L1 expression, and across all 3, we achieved an improvement in OS. There are many different studies right now testing pembrolizumab in the first-line setting. We are trying to hit the whole package.
- Mok T, Cheng Y, Zhou X, et al. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non–small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018;78,7994.
- Mok T, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib for the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer (ARCHER 1050): a randomized, open-label phase 3 trial. J Clin Oncol. 2017;35(suppl; abstr LBA9007)