Beyond Tumor Type: HER2 Link in Leukemia Setting Shows Molecular Profiling Potential
Published Online: Friday, September 21, 2012
Maurie Markman, MD
Editor-in-Chief of OncologyLive
Senior vice president for Clinical Affairs and National Director for Medical Oncology
Cancer Treatment Centers of America, Eastern Regional Medical Center
However, for the present, the large majority of treatment decisions continue to be based on standard morphologic classifications and specific molecular abnormalities observed to be relevant in a particular tumor type. For example, the language of clinical oncology continues to refer to “an activating EGFR mutation in non-small cell lung cancer,” rather than “an activating EGFR mutation in multiple (or all) tumor types” in defining the potential utility of a tyrosine kinase inhibitor of EGFR activity.
The impact of specific molecular abnormalities that can cross somewhat artificial morphologic barriers or the site of origin of a malignancy was strikingly highlighted by the demonstrated major clinical activity of imatinib against chronic myelocytic leukemia and gastrointestinal stromal tumors (GISTs). Despite remarkably different clinical characteristics, as well as histologies and locations within the body, a similar molecular defect characterizes their development and progression. In both cancers, the use of this molecularly targeted therapeutic has revolutionized care, and for many patients has turned the malignancies into very serious but manageable chronic illnesses.
Now, a second highly targeted antineoplastic drug has demonstrated impressive biological and clinical activity across vastly different cancer types. Trastuzumab, a well-characterized inhibitor of HER2, is a recognized standard-of-care in the management of HER2-overexpressing breast cancer in both the metastatic and adjuvant settings.2,3 More recent data have documented the clinical utility of this agent in gastric cancer in patients whose tumors overexpress the HER2 receptor.4
And in a most provocative report, investigators have confirmed biological and clinical activity associated with trastuzumab in a specific population of patients with B-cell adult acute lymphocytic leukemia (ALL) who exhibit evidence of upregulation of the HER2 receptor, a group that represents approximately one-third of all patients with this malignancy.5 Of 15 patients with chemotherapy-refractory disease who possessed this defined molecular abnormality, two (13%) achieved a partial response following delivery of single-agent trastuzumab, with an additional two patients experiencing clearance of blast cells.
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