CHICAGO — Updated phase 3 data from the ARCHER 1050 trial showed that dacomitinib improved OS compared with gefitinib among patients with newly diagnosed, advanced EGFR-positive non-small cell lung cancer.
The findings build on previous data that demonstrate dacomitinib (PF-00299804, Pfizer) significantly prolonged PFS vs. gefitinib (Iressa, AstraZeneca). According to final results presented at ASCO, dacomitinib prolonged OS by 7.3 months and PFS by 5.5 months. However, it was associated with a higher incidence of toxicity, according to Tony S. Mok, MD, chair of clinical oncology at The Chinese University of Hong Kong. Still, Mok said during a presentation that dacomitinib should be considered as a first-line treatment option for patients with an EGFR mutation, given its survival benefits.
Based on data from the ARCHER 1050 trial, the FDA granted priority review to dacomitinib for the treatment of patients with locally advanced or metastatic NSCLC with EGFR-activating mutations. However, Yanis Boumber, MD, PhD, assistant professor in the department of hematology/oncology at Fox Chase Cancer Center, said the approval of dacomitinib would have little impact on practice since its comparator has been replaced as the current gold standard of care with osimertinib (Tagrisso, AstraZeneca).
“I have my concerns with dacomitinib,” Boumber told HemOnc Today. “I would be nervous to put a patient on dacomitinib compared to osimertinib.”
Osimertinib was approved by the FDA in April as a first-line treatment option for metastatic non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Studies have shown that osimertinib is superior to gefitinib as well as erlotinib (Tarceva, Genentech). Therefore, even though the improvement in OS with dacomitinib vs. gefitinib is “an important finding,” Boumber said additional studies are needed to compare dacomitinib with this “better drug.” He said another major limitation of dacomitinib is that the drug has not been evaluated in patients with brain metastases.
“It is unknown what dacomitinib does to the brain,” Boumber said. “That’s a serious caveat.”
In contrast, Boumber said physicians are “quite confident” that osimertinib has “good brain efficacy.” As a result, the findings from the ARCHER 1050 are unlikely to be “practice-changing,” he said.
“Dacomitinib remains investigational at this point,” Boumber said. “There are two questions that are still unanswered: how does dacomitinib compare to osimertinib and how does it affect the brain? Whether these questions will be addressed is hard to say.” - by Stephanie Viguers
Mok T, et al. Abstract 9004. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Boumber reports serving on advisory boards for Bristol Myers, Takeda, AstraZeneca and Caris Life Sciences.