Paulus on Accelerating Clinical Development With Real-World Data in HER2+ Breast Cancer

“One of the achievements of this [research] was that we demonstrated that we were able to do this quickly and in lockstep with the [phase 2] trial as it enrolled.”

Jessica Paulus, ScD, the senior director of Observational Research at Ontada, discussed data from a pilot study that used real-world data to add an external control arm to a phase 2 trial (NCT05748834) of tucatinib (Tukysa) plus liposomal doxorubicin in patients with HER2-positive locally advanced or metastatic breast cancer.

In the pilot study, findings from which were presented during the 2025 ASCO Annual Meeting, investigators used real-world proxies for phase 2 eligibility criteria to create a simulated dataset and expand the 8 patients enrolled in the phase 2 study to a 40-patient dataset. The real-world external control arm contained 77 patients.

Following propensity score matching, findings from the study demonstrated that 82% (n = 33/40) of patients in the simulated cohort were successfully matched. The mean age in the phase 2 cohort was 61 years compared with 60 years in the real-world external control arm (SD, 0.03). Notably, the distribution of the number of prior treatments was similar between the 2 cohorts with 21% and 27% of patients in the phase 2 and real-world cohorts, respectively, having received 1 previous line of therapy (SD, 0.09).

Paulus noted that one of the achievements of the study was that investigators demonstrated that they were able to add patients quickly and simultaneously with the phase 2 trial as it enrolled using this methodology. Although gathering real-world data can be faster, there was a lot of effort put into patient matching in this portion, she added. Investigators were able to accurately match patients to the phase 2 trial to ensure the proper data elements were extracted, Paulus said.

Balance in terms of baseline characteristic matching was achieved in approximately 4 out of 6 baseline characteristics, Paulus explained. The remaining 2 variables were modestly out of balance, she added. Paulus also noted that findings presented at the 2025 ASCO Annual Meeting were from an interim analysis of the data. As more patients are added to the phase 2 study and the real-world arm, these differences are expected to be minimized, she concluded.