Lani
05-09-2012, 06:49 AM
of herceptin resistance
ABSTRACT: Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
[Journal of Clinical Oncology]
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.
OPEN ACCESS EDITORIAL: Doubling Down on Human Epidermal Growth Factor Receptor 2
[Journal of Clinical Oncology]
Major advances have been made in the treatment of HER2-positive breast cancer, and more are to come. There are several potent HER2-directed agents in late-stage clinical development, and combinations of anti-HER2 agents will provide new therapeutic opportunities. It is clear that HER2 remains an important target, even after multiple lines of therapy. Taken together, these observations will lead to longer and better lives for women with HER2-positive breast cancer and may ultimately allow us to cure women with metastatic disease. However, there is still much work to be done. As a community, we must push for tissue-based trials that will allow us to understand resistance and develop predictive biomarkers that will facilitate the optimal use of current and future therapies.
ABSTRACT: Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
[Journal of Clinical Oncology]
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.
OPEN ACCESS EDITORIAL: Doubling Down on Human Epidermal Growth Factor Receptor 2
[Journal of Clinical Oncology]
Major advances have been made in the treatment of HER2-positive breast cancer, and more are to come. There are several potent HER2-directed agents in late-stage clinical development, and combinations of anti-HER2 agents will provide new therapeutic opportunities. It is clear that HER2 remains an important target, even after multiple lines of therapy. Taken together, these observations will lead to longer and better lives for women with HER2-positive breast cancer and may ultimately allow us to cure women with metastatic disease. However, there is still much work to be done. As a community, we must push for tissue-based trials that will allow us to understand resistance and develop predictive biomarkers that will facilitate the optimal use of current and future therapies.