Erin Gourley Reid, MD
Today’s ASH/ASCO Joint Symposium session will highlight information important to understanding the diversity of genetic and epigenetic events leading to malignant transformation and unifying themes for the effective management of patients with solid tumor and hematologic malignancies. ASCO President Dr. George Sledge Jr. will join ASH President Dr. Hal Broxmeyer in chairing this exciting session.
Gleevec, pioneered as a treatment for CML, was found to be highly effective for the management of gastrointestinal stromal tumors (GIST), a relatively rare solid tumor that was unresponsive to all cytotoxic agents. As with CML, overexpression of a tyrosine kinase was the primary driver of malignancy in GIST tumors and blocking this pathway resulted in significant clinical responses. Similarly, the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib, originally developed for ALK+ lymphomas, has shown remarkable success in the treatment of patients with lung cancer harboring the ALK fusion gene; this study will be presented by Dr. Eunice Lee Kwak. Patients with ALK+ lung cancer are generally non-smokers and represent only about 4 percent of patients with non-small cell lung cancer. However, the ALK fusion gene is the dominant mutational event and interfering this kinase with crizotinib results in remarkable responses among patients with extensive prior chemotherapy.
Ipilimumab has a novel mechanism of action. By blocking the CTLA-4, it potentiates T-cell activation and is on the fast-track for FDA approval for melanoma. In the randomized phase III trial, overall survival was increased from 6.4 to 10 months, and 40 percent of patients were alive at one year and 20 percent were alive at two years — clinical results not previously seen in large-scale clinical trials for advanced melanoma. Multiple abstracts presented during the ASH meeting indicate that this drug may have activity among patients with recurrent or refractory lymphoma.
The last trial is an interesting contrast to the newer medications such as ipilimumab and crizotinib that achieve important clinical responses with fewer side effects than conventional chemotherapy. Dr. Elisabeth A. Quoix will discuss results of the phase III study comparing weekly paclitaxel combined with monthly carboplatin versus single-agent therapy in patients 70 to 89 years old with lung cancer. The intensity of treatment can correlate with clinical effectiveness but can also correlate with significant toxicity, especially for elderly patients. Combined chemotherapy is the standard for patients with advanced lung cancer but single-agent therapy is often given, particularly to elderly patients, to minimize toxicity. However, for selected patients, the choice of single-agent therapy to minimize toxicity may result in decreased overall survival. The development of less toxic therapies may significantly change the way we treat elderly patients.
Dr. Reid receives research funding from Millennium for an investigator-initiated study and is a PI for pharma-sponsored trials from BMS, Millennium, and Novartis.