A phase 3 trial has linked Pfizer’s dacomitinib to better overall survival (OS) than Iressa in nonsmall cell lung cancer (NSCLC). The results suggest Pfizer’s EGFR tyrosine kinase inhibitor is more effective than its aging rival but leave ample room to doubt its ability to outcompete AstraZeneca’s Tagrisso.
Pfizer presented progression-free survival (PFS) data from the phase 3 trial at the 2017 ASCO Annual Meeting and rolled up to this year’s meeting equipped with OS results. As with the PFS readout, the OS data suggest dacomitinib is more effective than Iressa. Participants in the dacomitinib arm had a mean OS of 34.1 months, compared to 26.8 months for their peers in the Iressa cohort. That resulted in a p-value of 0.0438.
The OS finding builds out Pfizer’s case as it moves toward its September PDUFA date. But other parts of the data suggest Pfizer may struggle to persuade doctors to prescribe dacomitinib over Tagrisso in first-line NSCLC. Tagrisso may have an edge in terms of safety and its ability to treat patients with CNS metastases.
Pfizer excluded people with CNS metastases from the phase 3 trial because of uncertainty about the ability of dacomitinib to cross the blood-brain barrier. In contrast, around one-fifth of participants in AstraZeneca’s FLAURA trial had CNS metastases. Responses were consistent across patients with and without the metastases, supporting AstraZeneca’s claim that its EGFR tyrosine kinase inhibitor is CNS active.
That is one issue Pfizer will face if dacomitinib comes to market. The other issue relates to safety. Investigators in the phase 3 needed to modify the dosing of two-thirds of people in the dacomitinib arm as a result of toxicities that were impossible to manage with supportive interventions. Around 39% of participants dropped down from 45mg a day to 30mg a day. Another 28% of people needed to drop to 15mg a day.
Grade four and above adverse events were rare and 90% of people in the dacomitinib arm stayed in the trial. On those metrics, dacomitinib looks like it can hold its own against Tagrisso. But the 4% rate of dose reduction in the Tagrisso study is vastly different than the 66% in the dacomitinib trial.
These factors will come into play when dacomitinib and Tagrisso start competing commercially. For now, Pfizer and its collaborators are focusing on the aspects of the trial that look set to secure FDA approval for dacomitinib later this year.
“What is most encouraging about these results is that patients with non-small cell lung cancer harboring EGFR-activating mutations who received dacomitinib achieved a median overall survival of nearly three years, a marked improvement compared to an established treatment in this setting,” Mace Rothenberg, M.D., Pfizer’s oncology chief development officer, said in a statement. “We are encouraged by these data and committed to deliver this promising investigational medicine to patients as quickly as possible.”