Pfizer Builds Case for Tukysa as ‘New Standard Regimen’ in First-Line Metastatic Breast Cancer

 

While new late-stage data point to some liver toxicity signals, analysts at BMO Capital Markets said Tukysa’s efficacy outcomes “appear to more than make up for any safety concerns.”

Pfizer’s oral kinase inhibitor Tukysa significantly cut the risk of death or disease progression in patients with metastatic breast cancer in the frontline setting.

Tukysa’s performance in this indication positions it to “become a new standard regimen” in HER2-positive metastatic breast cancer, analysts at BMO Capital Markets said in a Wednesday note. “Results today are a positive advancement. . .demonstrating more upside from expansion in oncology in the near term,” they added.

The Phase III trial was not without its setbacks, however, as BMO noted liver toxicities.

BMO considered the incidence of liver toxicity to be “meaningfully higher” with Tukysa treatment, something they expect doctors to take into account when deciding whether to prescribe the regimen. Still, “We expect most physicians to be comfortable with this risk trade-off,” the analysts wrote, “as efficacy outcomes appear to more than make up for any safety concerns.”

In the HER2CLIMB-05 study, Pfizer tested a combination of Tukysa and Roche’s Herceptin and Perjeta in more than 320 patients with HER2-positive metastatic breast cancer who had undergone pre-study induction treatment with Herceptin, Perjeta and taxane, and had shown no sign of disease progression thereafter. Patients in the control arm were treated with just Herceptin and Perjeta.

Results, announced Wednesday and presented at the 48th San Antonio Breast Cancer Symposium (SABCS), showed the Tukysa-based combo cut the risk of disease progression or death by 35.9% versus controls. Median progression-free survival (PFS) hit 24.9 months in the Tukysa arm, versus 16.3 months for comparators. Overall survival, which was immature at the time of the readout, leaned numerically in favor of Tukysa.

Pfizer also noted that Tukysa’s PFS benefit remained consistent across different patient subgroups, including those with recurrent or de novo diagnoses, with or without brain metastasis and whose disease was either HR-positive or HR-negative.

“Improvements in PFS of this magnitude are clearly significant and clinically meaningful,” BMO added in its note, “potentially opening the opportunity for [Tukysa] to be added as a standard 1L treatment option.”

Data from HER2CLIMB-05 also revealed potential safety concerns, including a higher rate of grade 3 and higher elevations in liver transaminases—though Pfizer insisted these were “typically manageable and reversible” with dose modifications. More detailed data published in the Journal of Clinical Oncology showed that 13.5% of patients dropped out due to treatment-emergent adverse events.

https://www.biospace.com/drug-development/pfizer-builds-case-for-tukysa-as-new-standard-regimen-in-first-line-metastatic-breast-cancer