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Molecularly Matched Cancer Treatments Extend Survival Times in Large, Early-Stage Study

CHICAGO (GenomeWeb) – Researchers involved in the University of Texas MD Anderson Cancer Center's "Initiative for Molecular Profiling in Advanced Cancer Therapy" (IMPACT) study have found evidence that molecularly matched treatments can improve overall survival outcomes for individuals with a range of cancer types.

During a press briefing held at the American Society of Clinical Oncology meeting here on Saturday, Apostolia Maria Tsimberidou, an investigational cancer therapeutics researcher at MD Anderson, presented data for 3,743 patients enrolled between 2007 and 2013 and molecularly profiled at anywhere from one to 50 cancer-related genes in a CLIA-certified lab. When actionable mutations were detected, the individuals received targeted treatments, including investigational compounds and US Food and Drug Administration-approved drugs used off label.

"We hypothesized that tumor molecular profiling would optimize the selection of cancer therapy, leading to improved outcomes compared to the standard approach," she said.

The patients included those with rare cancer types, along with individuals who had relapsed on as many as 16 prior therapies, Tsimberidou noted. Just 2.8 percent of the individuals had not been treated previously. The most common cancer types represented in the group included gastrointestinal, gynecological, breast, and lung cancers as well as melanoma.

The researchers unearthed one or more targetable mutations in 1,307 cases, or nearly 35 percent of the cases considered. Of those, more than half of the individuals — 711 cases — received matched targeted therapy, while the remaining 596 individuals got non-molecularly matched therapies.

In the molecularly matched arm of the study, the team saw an objective response rate of 16.2 percent, and another 18.7 percent of cases with stable disease stretching out for six months or more. In contrast, the objective response rate was just over 5 percent in the non-matched group, and 14.7 percent of individuals in that arm had stable disease for at least six months.

The median progression-free survival time in the molecularly targeted treatment group was four months compared to 2.8 months in the non-matched group, Tsimberidou reported, while overall survival was a median of 9.3 months in the matched group relative to 7.3 months in non-matched patients.

Similarly, some 15 percent of the patients receiving matched therapy had overall survival times of at least three years, and 6 percent reached overall the 10 year survival point. In contrast, just 7 percent of the non-matched treatment group reached the three-year overall survival point with 10 year overall survival of just 1 percent.

In their multivariate analysis, meanwhile, the researchers found evidence that matched therapy was an independent factor in overall survival, along with well-documented risk factors such as age, PI3 kinase/ACT/mTor pathway alterations, or liver metastasis. From these data, they went on to establish a 0- to 7-point prognostic score that took such risk factors, including matched therapy, into account.

Indeed, Tsimberidou said, "matched targeted therapy was an independent factor associated with longer overall survival."

Commenting on the phase 1 IMPACT study during the ASCO briefing, Catherine Diefenbach, a hematology and medical oncology researcher at New York University's Langone Medical Center and ASCO expert, commended the investigators for demonstrating a survival impact of genetically matched treatment in advanced cancers, noting that "to treat cancer based on neighborhood ignores genetic differences."

Findings from that exploratory analysis are scheduled to appear during a poster session on developmental therapeutics at the American Society of Clinical Oncology annual meeting this morning. The MD Anderson-led team plans to continue exploring the feasibility of molecularly targeted therapy and precision medicine in a randomized phase 2 clinical trial called IMPACT2.

The latter study — which will involve profiling on far more cancer-related genes, as well as analyses of other informative and immune markers — is expected to expand on the data available through other large efforts such as the ASCO study TAPUR and the National Cancer Institute's NCI-MATCH program, which are exploring the potential benefits of matching tumor alterations to specific targeted treatments.

Also at this week's ASCO conference, investigators from several centers provided updates on three treatment arms of NCI-MATCH, including data on the modestly performing experimental PI3K inhibitor taselisib that was tested in PIK3CA-mutated tumors.