Missak Haigentz, MD
The identification of sensitizing mutations along with the development of EGFR tyrosine kinase inhibitors (TKI) has been crucial to selecting the right treatment for select patients with non–small cell lung cancer (NSCLC), said Missak Haigentz, MD.
In September 2018, the FDA approved dacomitinib (Vizimpro) for the frontline treatment of patients with EGFR
-positive NSCLC who harbor exon 19 deletion or exon 21 L858R substitution mutations. The approval was based on data from the phase III ARCHER 1050 trial, in which the second-generation TKI dacomitinib reduced the risk of progression or death by more than 40% compared with gefitinib (Iressa).
Data presented at the 2018 ASCO Annual Meeting showed that the median overall survival (OS) was 34.1 months in patients randomized to dacomitinib versus 26.8 months in those randomized to gefitinib. Median progression-free survival (PFS) for patients on the dacomitinib arm was 14.7 months compared with 9.2 months for those who received gefitinib (HR, 0.59; 95% CI, 0.47-0.74; P
<.0001). The median duration of response was 14.8 months with dacomitinib versus 8.3 months with gefitinib (HR, 0.40; 95% CI, 0.31-0.53; P
This approval followed that of osimertinib (Tagrisso), a third-generation EGFR TKI that was approved as a frontline treatment for patients with EGFR
-mutant NSCLC in April 2018.
Haigentz, chief of Hematology and Oncology at Morristown Medical Center and medical director of Atlantic Hematology and Oncology for Atlantic Medical Group at the Carol G. Simon Cancer Center, noted that the next step for thoracic oncologists is the research of sequencing strategies for this class of agents, which also includes afatinib (Gilotrif) and erlotinib (Tarceva). The treatment-related adverse events highlighted in ARCHER 1050 is also something to consider, he added.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Non–Small Cell Lung Cancer, Haigentz discussed the impact of EGFR TKIs on the treatment of patients with NSCLC.
OncLive: Please provide an overview of your presentation.
: The way that we view lung cancer compared with how we have viewed lung cancer in the past has drastically changed. It has changed over the last 20 years since I have been a fellow. We viewed lung cancer as a single disease where we knew of histological entities. Now, we view it as a large number of molecularly defined cancer types and genotypes for which we now have targetable mutations that are actionable and making huge differences in patients' lives.
I spoke about the EGFR
mutation and the subset of patients who have sensitizing EGFR
mutations. In the United States, this accounts for about 15% to 20% of NSCLC cases. In other parts of the world, this can be around 40% to 50%. These mutations tend to happen in never-smokers but can happen anywhere. It's a testament to translational science and cancer genomics that we've been able to identify patients at the right time to get the right drug.
Over my career, the development of EGFR TKIs since 2003 has been exciting to see. It's hard to imagine it's been 15 years. They started initially for unselected patients, but now over the last 5 years, we have several drugs that are FDA approved for patients with EGFR-
positive NSCLC. These drugs have been developed over 3 generations. The generations have been associated with incremental increases in PFS over chemotherapy to the point where we no longer use chemotherapy as the standard frontline treatment.
Even in the past year, we now have 2 FDA-approved agents added to the armamentarium. I spoke about these 2 agents, which are osimertinib and dacomitinib. These are third- and second-generation TKIs, respectively. With dacomitinib as a single agent, we've finally seen a change in OS, which has been elusive. The question is, "Where do these fit into the landscape?"
Has the September 2018 approval of dacomitinib had an immediate impact on your practice?
It's going to be an interesting challenge as far as selecting these agents for frontline treatment. In the ARCHER 1050 study, which is what led to the FDA approval, we saw an improvement in OS. It was a secondary endpoint, but it was the first time we saw an improvement in this area in a head-to-head comparison of 2 EGFR inhibitors. Dacomitinib was compared with gefitinib.