Adding pertuzumab to trastuzumab effective for HER2-positive breast cancer
medwireNews: Adding pertuzumab to trastuzumab plus an aromatase inhibitor (AI) may be effective for patients with human HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer, a phase II trial suggests.
First-line treatment with the triple combination and optional induction chemotherapy significantly reduced the chance of disease progression or death by 35%, compared with just trastuzumab plus an AI among 258 postmenopausal women enrolled in the PERTAIN trial.
The women enrolled from 80 sites in eight countries were randomly assigned to receive intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg followed by 6 mg/kg every 3 weeks) and oral anastrozole (1 mg/day) or letrozole (2.5 mg/day), or trastuzumab and an AI. None of the participants had prior systemic therapy apart from endocrine.
Median time to progression-free survival (PFS), defined as first radiographically documented progression of disease or death, was 18.89 months for women receiving pertuzumab plus trastuzumab and an AI, compared with 15.80 months for those receiving trastuzumab plus an AI in the open-label trial.
PFS benefit with the addition of pertuzumab was also seen in the subgroup of 112 patients not receiving induction chemotherapy, at a median 21.72 months for the 54 patients in the pertuzumab plus trastuzumab arm versus 12.45 months for the 58 in the trastuzumab only arm, at a significant hazard ratio of 0.55.
The researchers report in the Journal of Clinical Oncology that the safety profile was consistent with prior trials of pertuzumab plus trastuzumab and there were no new safety signals.
Serious adverse events were reported for 42 (33.1%) of 127 patients in the safety population receiving additional pertuzumab and in 24 (19.4%) of the 124 patients receiving trastuzumab alone. Adverse events of grade 3 or more occurred in 50.4% versus 38.7%, respectively, and there were no deaths.
Among secondary efficacy endpoints, there was a nonsignificant trend toward a higher number of responders among patients receiving additional pertuzumab versus trastuzumab plus AI alone, which was mainly driven by complete responses that occurred in 7.3% versus 0.9% of the two groups, respectively.
“Pertuzumab and trastuzumab bind to different epitopes on HER2, which provides a more comprehensive signaling blockade and leads to greater activity compared with monotherapy,” the researchers led by Mothaffar Rimawi (Baylor College of Medicine, Houston, Texas, USA) write.
“Preclinical models have also suggested that this may inhibit HER2–estrogen receptor crosstalk more efficiently, enhancing the antitumor activity of tamoxifen or estrogen deprivation.”
By Anita Chakraverty
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