Genomic testing of tumor samples can enable personalized treatment selection, where targeted treatments are matched to genetic changes in the tumor. Although a growing number of patients with advanced cancers receive some genomic testing, comprehensive genomic testing is not yet routine care.
A study in France of 1,944 patients with advanced cancer suggests that widespread, routine genomic testing is feasible, althoughat this time, it may offer clinical benefit to only a subset of patients. According to the authors, this is the largest study of its kind. The study was presented today by Tredan et al at the 2017 ASCO Annual Meeting (Abstract LBA100).
The researchers found at least one actionable alteration in 52% of the tumor samples tested. A molecular tumor board recommended targeted treatments to 676 patients, and 143 of them received the recommended treatment. The 5-year survival rate was higher among patients who received the recommended treatment than among those who did not (34.8% vs 28.1%).
“This study confirms that comprehensive genomic profiling can be performed in routine practice to select patients for targeted cancer therapies,” said lead study author Olivier Tredan, MD, PhD, Chair of the Department of Medical Oncology at the Centre Léon Bérard in Lyon, France. “The technology is widely available and requires only a small amount of DNA. Theoretically, we could do this testing for every patient in France.”
About the Study
ProfiLER is an ongoing clinical trial that uses genomic profiling of tumors to guide treatment decisions for patients with advanced cancer. DNA from tumor samples is analyzed by next-generation sequencing of 69 cancer-related genes and whole-genome comparative genomic hybridization. Both technologies are widely available in France and elsewhere in the world, according to the authors. A multidisciplinary board of experts (the molecular tumor board) meets weekly to review genomic testing results and, if actionable mutations are found, provides recommendations for molecularly targeted therapies.
“We recommended molecularly targeted therapies to patients who had mutations in pathways that could be targeted with either commercially available drugs or those tested in early clinical trials,” said Dr. Tredan.
To date, 2,676 patients have enrolled in the study, and 1,944 tumors were analyzed, including colorectal, gynecologic, breast, brain, and head and neck, as well as sarcoma. Actionable mutations were found in 1,004 tumor samples (52%); 609 patients had only 1 actionable mutation, and 394 patients had 2 or more (up to 6).
The most common actionable pathway was the PI3K/mTOR pathway. The molecular tumor board recommended molecularly targeted treatments to 676 patients (35% of 1,944 tested) based on the availability of drugs hitting either the target protein or the pathway activated by the target. Of them, 143 received the recommended treatment, most through enrollment in a clinical trial. The other 533 patients were not able to receive the recommended treatment because of poor health/rapid progression of the cancer, not meeting eligibility criteria for a clinical trial, or difficulty obtaining off-label commercial medicines.
Researchers compared overall survival rates for the 143 patients who received targeted therapies based on genomic testing and 502 patients who did not. At 3 years, 53.7% of patients who received the recommended targeted therapy were alive, compared with 46.1% of patients who did not. The 5-year survival rate was also higher for patients who received targeted therapy (34.8% vs 28.1%).
“This study gives more validation for the use of genomics in clinical practice and shows it could very well guide treatment choices for patients with advanced cancer. These data are particularly interesting in the face of recent approvals for immunotherapy for patients who have evidence of genomic instability,” said ASCO expert Sumanta Kumar Pal, MD.
This study was funded by LYRIC and BPI France Financement abounded by European Community.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.