Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 1026
© 2008 American Society of Clinical Oncology

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Abstract

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

British Columbia Cancer Agency, Vancouver, BC, Canada; Centre Georges-François-Leclerc, Dijon, France; Ottawa Regional Cancer Center, Ottawa, ON, Canada; Christie Hospital, Manchester, United Kingdom; University Hospital, Modena, Italy; Mount Vernon Cancer Centre, Middlesex, United Kingdom; Oncologia Medica, Milan, Italy; Roche Products Limited, Welwyn, United Kingdom; Vall d'Hebron University Hospital, Barcelona, Spain

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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 This pt was withdrawn due to progressive disease.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.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche, sanofi-aventis Roche F. Hoffmann-La Roche, Roche, sanofi-aventis F. Hoffmann-La Roche, Roche, Roche Canada Roche

Abstract presentation from the 2008 ASCO Annual Meeting