Matching treatment to genetic changes in the tumor improves survival

<p class="article-intro">A retrospective analysis of consecutive, prospectively molecularly profiled patients with advanced cancer who participated in a large, personalized medicine trial revealed that using molecular tests of tumors to select targeted therapy resulted in slower cancer growth and prolonged survival across a diverse set of cancer types.</p> <hr /> <p class="article-content"><p>The IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) clinical trial began in 2007 to evaluate the impact of personalized therapy selection based on molecular testing of tumors for people with difficult-to-treat cancers. Patients referred to the study had advanced cancer that worsened despite standard treatment (some had received as many as 16 prior therapies). Very few patients (2,8 % ) were newly diagnosed with a rare, incurable cancer. The most common types of cancer included gastrointestinal cancer, gynecologic cancer, breast cancer, melanoma, lung cancer, and thyroid cancer. <br />In the early years of the study, tumors were tested for mutations in individual genes, whereas in the late years of the study (until the end of 2013), next generation sequencing was used to test 20-50 different genes at once. Of the 3743 patients who had molecular testing, at least one genetic change was found in 1307 tumors. Of those, 711 patients received treatment matched to the biology of the tumor and 596 received a therapy that was not matched to the genetic change found in the tumor (i.e. because no matched treatment was available to the patient at the time). Matched therapies included single agent targeted therapy, as well as matched targeted therapy in combination with chemotherapy, or other treatments.</p> <p>Overall survival in the matched targeted therapy group plateaued, starting at 3,2 years (11 % were still alive). Matched targeted therapy was found to be an independent factor predicting longer overall survival in multivariate analysis. The 3-year overall survival rate was 15 % in the matched therapy group compared to 7 % in the non-matched group. The 10-year overall survival rate was 6 % for the matched therapy group and 1 % in the non-matched group. The median overall survival was longer in the matched therapy group versus the non-matched therapy group (9,3 months vs. 7,3 months), as was the median time until cancer worsened (progression-free survival: 4 months vs. 2,8 months). <br />The investigators developed a prognostic score to predict overall survival of patients based on their baseline characteristics. Taking into consideration baseline characteristics in 1307 patients, molecular alterations in the PI3K/AKT/mTOR pathway were an independent factor predicting shorter overall survival compared to other alterations. Other independent factors predicting shorter survival were liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age &ge;60 yrs.</p> <p>The ongoing follow-on study, IMPACT 2, is a randomized phase-II-study comparing progression-free survival in patients who receive targeted therapy matched to the molecular characteristics of their tumor versus in those for whom treatment is not selected based on the molecular analysis of their tumor. Dr. Tsimberidou notes that the implementation of precision medicine using next-generation sequencing, as well as immune features and new drugs, including immunotherapy, hold the promise to significantly improve the clinical outcomes of patients with cancer.</p> <p><strong>Reference:</strong> <br />Tsimberidou AM et al.: Precision Medicine: Clinical Outcomes including Long-Term Survival According to the Pathway Targeted and Treatment Period: The IMPACT Study. ASCO Annual Meeting 2018, abstract #LBA2553</p></p>