Bringing the Oncology Community Together

Beyond Tumor Type: HER2 Link in Leukemia Setting Shows Molecular Profiling Potential

Maurie Markman, MD
Published Online: Friday, September 21, 2012
Maurie Markman, MD

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

The truly spectacular advances in genetic sequencing technology herald an era where it will be possible to provide a blueprint of specific actionable abnormalities within individual cancers with a time frame of a few days to several weeks, and at an equivalent or perhaps lower cost than that associated with many currently routine laboratory tests.1 It is highly likely that this genuine revolution in our understanding of the biology of individual cancers will permit in the relatively near future far more precise antineoplastic management for many, if ultimately not most, cancers.

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

Snapshot of Phase II GRAALL Study

Eligibility Criteria
  • ≥18 y
  • Relapsed/refractory B-ALL
  • HER2+ for ≥30% leukemic blast population in peripheral blood and/or bone marrow
Number of Patients 50 patients screened
15 patients selected
  • 62 y median age (24-80 y)
  • 2 patients refractory after 2 induction courses
  • 2 patients in first untreated relapse
  • 11 patients refractory or beyond first relapse
Trastuzumab dosing 4 mg/kg intravenous loading dose followed by 2 mg/kg weekly

B-ALL indicates B-cell acute lymphoblastic leukemia.

Source: Chevallier P, Robillard N, Charbonnier A, et al. Trastuzumab (Herceptin®) for treatment of refractory/relapsed HER2 positive adult B-ALL: results of a phase II GRAALL study. Blood (ASH Annual Meeting Abstracts). 2011;118: abstr 1525.

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.

Page: 12Next Page (2) >>
Related Articles
Case Study: HER2-Positive Oligometastatic Breast Cancer
In this segment, panelists explore the treatment of a 40-year-old woman with a 2 cm mass in her left breast and a 2 cm liver lesion, both of which test positive for HER2 overexpression.
FDA Approves First-Line Ofatumumab for Fludarabine-Ineligble Patients With CLL
The FDA has approved ofatumumab plus chlorambucil for previously untreated patients with chronic lymphocytic leukemia who are considered inappropriate for treatment with fludarabine therapy.
Phase III Clinical Trials in HER2-Positive Breast Cancer
Expert panelists explore several large clinical trials examining therapies for patients with HER2-positive breast cancer that are currently ongoing or have recently completed.
Next-Generation Targeted Therapies in NSCLC
In this segment, panelists discuss the number of early-phase clinical trials that have demonstrated impressive efficacy for next-generation ALK and EGFR inhibitors for patients with non-small cell lung cancer.
Most Popular Right Now
More Reading
External Resources

American Journal of Managed Care
HCPLive
PainLive
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Specialty Pharmacy Times
TargetedOnc
OncLive Resources

Archives
Blogs
OncLive TV
Oncology Nurses
Publications
Specialties
Web Exclusives


About Us
Advertise
Advisory Board
Contact Us
Forgot Password
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright OncLive 2006-2014
Intellisphere, LLC. All Rights Reserved.