Author(s): Corts J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K,
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Abstract PURPOSE: The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50\% in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy. PATIENTS AND METHODS: Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg every 3 weeks). RESULTS: All 29 patients enrolled for pertuzumab monotherapy experienced disease progression. The objective response rate (ORR) and CBR were 3.4\% and 10.3\%, respectively, during pertuzumab monotherapy. With the addition of trastuzumab, the ORR and CBR were 17.6\% and 41.2\%, respectively. Progression-free survival was longer with combination therapy than pertuzumab monotherapy (17.4 v 7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac dysfunction. CONCLUSION: Although pertuzumab has some activity in patients with HER2-positive breast cancer that progressed during therapy with trastuzumab, the combination of pertuzumab and trastuzumab seems to be more active than monotherapy.
This article was published in J Clin Oncol
and referenced in Biochemistry & Pharmacology: Open Access