Targeted therapies matched to specific gene mutations in patients’ tumors yielded longer progression-free and overall survival durations than did nonmatched therapies in an analysis of long-term data from a study at The University of Texas MD Anderson Cancer Center.
In the ongoing “umbrella” study (IMPACT, No. 2007-0885), patients with advanced, refractory solid cancers who have been referred to phase I clinical trials at MD Anderson undergo molecular testing of their tumors. In a recent analysis of 3,743 patients who had undergone such testing, 1,307 had at least one molecular alteration in their cancer and received matched targeted therapy (n = 711) or nonmatched therapy (n = 596) given alone or combined with other anticancer drugs, depending on the trials.
“We hypothesized that genetic and molecular analysis of solid tumors could enable the selection of optimal therapy,” said Apostolia Tsimberidou, M.D., Ph.D., a professor in the Department of Investigational Cancer Therapeutics and the study’s principal investigator.
In the analysis, the median progression-free and overall survival durations were significantly longer for patients who received matched targeted therapy (4.0 and 9.3 months) than for those who received nonmatched therapy (2.8 and 7.3 months). The 3-year overall survival rate was 15% in the matched targeted therapy group and 7% in the nonmatched therapy group. And the 10-year overall survival rate was 6% in the matched targeted therapy group and 1% in the nonmatched therapy group. Alterations in the PI3K/AKT/mTOR pathway were associated with shorter progression-free and overall survival durations.
The analysis also revealed several prognostic factors. In addition to treatment with matched targeted therapy, independent predictors of longer overall survival included normal lactate dehydrogenase levels, functional status, albumin levels, and platelet counts and the absence of liver metastases or PI3K/AKT/mTOR alterations.
Dr. Tsimberidou and colleagues presented their findings at the American Society of Clinical Oncology annual meeting in June (abstract No. LBA2553). The researchers are now conducting a randomized phase II trial (IMPACT2, No. NCT02152254) to confirm the benefits of matched targeted therapy. “Ideally, in the future, tumor testing and cell-free DNA analysis at the time of patients’ diagnosis will become the standard of care,” Dr. Tsimberidou said.