Abstract
4070 Background: In metastatic pancreatic cancer (mPaCa) overexpression of the HER2 receptor has been reported in up to 82% of cases, suggesting its use as a therapeutic target. Therefore, the study was conducted to determine the efficacy and toxicity of capecitabine (CAP) and trastuzumab (TRAS) in pts with mPaCa. Methods: Eligible pts had histologically confirmed mPaCa. The primary endpoint was PFS at 12 weeks. Pts with mPaCa immunohistochemically overexpressing HER2 grade 3 or grade 2 with gene amplification (FISH) received TRAS 4 mg/kg initially followed by weekly 2 mg/kg combined with CAP 1,250 mg/m2 bid day 1-14, q21. The study with planned 37 pts was prematurely closed due to unexpected low HER2 expression. Results: Between May 1994 and February 1998 a total of 212 pts with a median age 64 years (range 38-86) were centrally screened for HER2 expression. In 207 pts the tumor specimens could be assessed for HER2 expression and gene amplification: By IHC 83 (40%) were grade 0, 71 (34%) grade 1, 31 (15%) grade 2, and 22 (11%) grade 3, respectively. One IHC grade 2 and all IHC grade 3 specimens showed gene amplification by FISH. From the 23 pts with HER2 gene amplification 17 could be assessed for response to treatment and toxicity in an intention- to treat analysis. Reported grade 3/4 toxicities in 88 cycles of chemotherapy were: leucopenia 6%, diarrhea 6%, nausea 6%, hand-foot syndrome 6%. There was no TRAS-attributable cardiac toxicity. PFS at 12 weeks was 23,5%, the median OS was 7.0 months. Conclusions: In contrast to previous findings, this multi-center study demonstrated HER2 overexpression and gene amplification in only 11% of pts with mPaCa. This discrepancy can be explained by the use of centrally reviewed standardized HER2 test methods and the examination of a large unselected cohort in the present study. Although the therapy was well tolerated, PFS and OS did not perform favourably compared to standard gemcitabine chemotherapy even if considering the exclusion of locally advanced PaCa in this cohort. Due to the low HER2 overexpression found in this study we do not recommend further evaluation of anti-HER2 treatment in pts with mPaCa. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
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