Lani
06-06-2008, 09:49 AM
Half of Metastatic Breast Cancer Patients Achieve Clinical Benefit With Experimental Pertuzumab Therapy: Presented at ASCO
CHICAGO — June 5, 2008 — The combination of trastuzumab and the experimental human epidermal receptor dimerisation inhibitor, pertuzumab, is active in patients with human epidermal growth factor receptor (HER2)-positive metastatic breast cancer that has progressed with treatment on trastuzumab.
Treatment with the combination of trastuzumab and pertuzumab resulted in a clinical benefit rate of 50% in patients with HER2-positive metastatic breast cancer, said investigator Graham Ross, MD, Roche Products Limited, Welwyn Garden City, United Kingdom.
In a poster presentation on June 3 here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting, Dr. Ross discussed the results of a single-arm, 2-stage, phase 2 study of 66 patients whose metastatic breast cancer had progressed despite treatment with trastuzumab.
Trastuzumab targets the overexpressed HER2 receptor found in breast cancer tumours, Dr. Ross explained, while pertuzumab attaches earlier in the molecular cascade that activates the gene believed to be responsible for cancer growth.
ASCO 2008: ABSTRACT #1026: Results of a phase II trial of trastuzumab (H) and pertuzumab (P) in patients (pts) with HER2-positive metastatic breast cancer (MBC) who had progressed during trastuzumab therapy
American Society of Clinical Oncology
Background: P is a humanized monoclonal antibody that binds to the specific dimerization epitope of HER2, blocking HER2 homo- and heterodimerization, thus preventing signal transduction. Xenograft studies indicate that the complementary mechanisms of action of P and H have a synergistic effect.
Methods: This single-arm, Simon-type, two-stage phase II trial included pts with measurable, centrally tested HER2-positive MBC, >3 lines of prior therapy (including adjuvant therapy), disease progression during prior H therapy, and a baseline LVEF >55% that had not declined to <50% with H therapy. Consenting pts received H at 2 mg/kg qw (4 mg/kg loading dose [LD]) or 6 mg/kg q3w (8 mg/kg LD) plus P at 420 mg q3w (840 mg LD) starting within 9 weeks of the last dose of H. LVEF was assessed regularly in all pts. The primary endpoint was objective response and clinical benefit response rate (OR and SD >6 mths).
Results: 66 pts have been enrolled and all have received >2 doses of study medication (41 are still on treatment). 63 pts have experienced >1 AE. Frequent AEs of all causes included diarrhea (63%), pain (35%), nausea/vomiting (30%), mucositis (32%), skin (27%), and rash (26%). Only 3 treatment-related AEs of severity G3, and none of G4, have been observed (diarrhea, pruritic rash due to contrast dye allergic reaction and a central line infection), all of which resolved and treatment continued. In addition 1 pt had a protocol-defined AE of special significance; an asymptomatic fall in LVEF of >10%-<50% based on a local reading which was not centrally confirmed. This pt was withdrawn due to progressive disease. No pts withdrew due to treatment-related or cardiac AEs. Preliminary RECIST response data (Baselga, ASCO 2007) are as follows: objective responses were seen in 6 of the 33 evaluable pts (1 CR, 5 PRs). Additionally, 7 pts achieved SD >6 mths and 10 pts SD <6 mths.
Conclusions: The combination of H and P was well tolerated and active in pts with MBC whose disease had progressed during therapy with H. Biomarker data from this study are being analyzed. Further studies in pts with MBC and early breast cancer are ongoing.
CHICAGO — June 5, 2008 — The combination of trastuzumab and the experimental human epidermal receptor dimerisation inhibitor, pertuzumab, is active in patients with human epidermal growth factor receptor (HER2)-positive metastatic breast cancer that has progressed with treatment on trastuzumab.
Treatment with the combination of trastuzumab and pertuzumab resulted in a clinical benefit rate of 50% in patients with HER2-positive metastatic breast cancer, said investigator Graham Ross, MD, Roche Products Limited, Welwyn Garden City, United Kingdom.
In a poster presentation on June 3 here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting, Dr. Ross discussed the results of a single-arm, 2-stage, phase 2 study of 66 patients whose metastatic breast cancer had progressed despite treatment with trastuzumab.
Trastuzumab targets the overexpressed HER2 receptor found in breast cancer tumours, Dr. Ross explained, while pertuzumab attaches earlier in the molecular cascade that activates the gene believed to be responsible for cancer growth.
ASCO 2008: ABSTRACT #1026: Results of a phase II trial of trastuzumab (H) and pertuzumab (P) in patients (pts) with HER2-positive metastatic breast cancer (MBC) who had progressed during trastuzumab therapy
American Society of Clinical Oncology
Background: P is a humanized monoclonal antibody that binds to the specific dimerization epitope of HER2, blocking HER2 homo- and heterodimerization, thus preventing signal transduction. Xenograft studies indicate that the complementary mechanisms of action of P and H have a synergistic effect.
Methods: This single-arm, Simon-type, two-stage phase II trial included pts with measurable, centrally tested HER2-positive MBC, >3 lines of prior therapy (including adjuvant therapy), disease progression during prior H therapy, and a baseline LVEF >55% that had not declined to <50% with H therapy. Consenting pts received H at 2 mg/kg qw (4 mg/kg loading dose [LD]) or 6 mg/kg q3w (8 mg/kg LD) plus P at 420 mg q3w (840 mg LD) starting within 9 weeks of the last dose of H. LVEF was assessed regularly in all pts. The primary endpoint was objective response and clinical benefit response rate (OR and SD >6 mths).
Results: 66 pts have been enrolled and all have received >2 doses of study medication (41 are still on treatment). 63 pts have experienced >1 AE. Frequent AEs of all causes included diarrhea (63%), pain (35%), nausea/vomiting (30%), mucositis (32%), skin (27%), and rash (26%). Only 3 treatment-related AEs of severity G3, and none of G4, have been observed (diarrhea, pruritic rash due to contrast dye allergic reaction and a central line infection), all of which resolved and treatment continued. In addition 1 pt had a protocol-defined AE of special significance; an asymptomatic fall in LVEF of >10%-<50% based on a local reading which was not centrally confirmed. This pt was withdrawn due to progressive disease. No pts withdrew due to treatment-related or cardiac AEs. Preliminary RECIST response data (Baselga, ASCO 2007) are as follows: objective responses were seen in 6 of the 33 evaluable pts (1 CR, 5 PRs). Additionally, 7 pts achieved SD >6 mths and 10 pts SD <6 mths.
Conclusions: The combination of H and P was well tolerated and active in pts with MBC whose disease had progressed during therapy with H. Biomarker data from this study are being analyzed. Further studies in pts with MBC and early breast cancer are ongoing.