Meeting NewsPerspective

Matched targeted therapy may enhance clinical outcomes for various cancers

Apostolia Maria Tsimberidou
Apostolia Maria Tsimberidou

CHICAGO — The use of next-generation sequencing on tumors to match therapy to genetic changes within tumors slowed cancer growth and prolonged survival among patients with various cancers, according to results from a retrospective analysis of the IMPACT clinical trial presented at ASCO Annual Meeting.

The IMPACT clinical trial — initiated in 2007 — measures personalized therapy selection based on molecular testing of tumors for individuals with difficult-to-treat cancers.

“We hypothesized that selection of therapy based on patients’ tumor molecular analysis will improve clinical outcomes compared with the standard approach,” Apostolia Maria Tsimberidou, MD, PhD, professor in the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, said during a press conference.

A majority of patients referred for the study had advanced cancer — gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), lung (8.7%) and melanoma (11.9%) — and disease that progressed with prior therapies.

At the start of the trial, researchers tested tumors for mutations in individual genes. However, over time, they started using next-generation sequencing to test multiple genes at once.

In the trial, 3,743 patients underwent molecular testing. Researchers detected at least one genetic change in tumors of 1,307 patients (median age, 57 years; 39% men; median prior therapies, 4; range, 0-16).

Of these patients, 711 patients received treatment that matched the biology of the tumor — an agent being investigated in a clinical trial — and 596 patients received treatment that was not matched to the genetic change found in the tumor because there were no available matched therapies. The latter group received a commercially available therapeutic approved by the FDA for another indication.

Matched therapies included targeted therapy as a single agent or in combination with chemotherapy or other treatments.

Among all patients with at least one genetic change in their cancer, the 3-year OS rate was 15% in the matched therapy group compared with 7% in the nonmatched group. Beginning at 3.2 years, OS in the matched therapy group plateaued.

The 10-year OS rate was 6% for the matched-targeted group and 1% for the nonmatched group.

Multivariate analysis showed matched targeted therapy was an independent factor for the prediction of longer OS (P < .001).

The median OS was 9.3 months in the matched therapy group compared with 7.3 months in the nonmatched therapy group. PFS also was longer in the matched therapy group (4 months vs. 2.8 months).

When considering baseline characteristics, molecular alterations in the PI3K/AKT/mTOR pathway were an independent factor that predicted shorter OS (HR = 1.22; 95% CI, 1.08-1.38) compared with other molecular alterations. Other independent factors for poorer OS included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts and age 60 years or older.

The randomized phase 2 IMPACT study will compare PFS among patients who receive targeted therapy matched to the molecular characteristics of their tumor to patients whose treatment is not selected based on the molecular analysis of their tumor, Tsimberidou said.

The implementation of precision medicine using next-generation sequencing may lead to significantly improved clinical outcomes among patients with cancer.

“I am optimistic within the next few years we will dramatically improve the outcomes for patients with cancer with increasing implementation of precision medicine,” Tsimberidou said. – by Melinda Stevens

Reference:

Tsimberidou AM, et al. Abstract LBA2553. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

 

Disclosures: Tsimberidou reports a consultant/advisory role with Roche and research funding to her institution from Baxter, Bayer, Boston Biomedical, EMD Serono, Foundation Medicine, IMMATICS, Karus Therapeutics, ONYX, Placon and Stem Cells, Inc. Please see the abstract for all other authors’ relevant financial disclosures.

Apostolia Maria Tsimberidou
Apostolia Maria Tsimberidou

CHICAGO — The use of next-generation sequencing on tumors to match therapy to genetic changes within tumors slowed cancer growth and prolonged survival among patients with various cancers, according to results from a retrospective analysis of the IMPACT clinical trial presented at ASCO Annual Meeting.

The IMPACT clinical trial — initiated in 2007 — measures personalized therapy selection based on molecular testing of tumors for individuals with difficult-to-treat cancers.

“We hypothesized that selection of therapy based on patients’ tumor molecular analysis will improve clinical outcomes compared with the standard approach,” Apostolia Maria Tsimberidou, MD, PhD, professor in the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, said during a press conference.

A majority of patients referred for the study had advanced cancer — gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), lung (8.7%) and melanoma (11.9%) — and disease that progressed with prior therapies.

At the start of the trial, researchers tested tumors for mutations in individual genes. However, over time, they started using next-generation sequencing to test multiple genes at once.

In the trial, 3,743 patients underwent molecular testing. Researchers detected at least one genetic change in tumors of 1,307 patients (median age, 57 years; 39% men; median prior therapies, 4; range, 0-16).

Of these patients, 711 patients received treatment that matched the biology of the tumor — an agent being investigated in a clinical trial — and 596 patients received treatment that was not matched to the genetic change found in the tumor because there were no available matched therapies. The latter group received a commercially available therapeutic approved by the FDA for another indication.

Matched therapies included targeted therapy as a single agent or in combination with chemotherapy or other treatments.

Among all patients with at least one genetic change in their cancer, the 3-year OS rate was 15% in the matched therapy group compared with 7% in the nonmatched group. Beginning at 3.2 years, OS in the matched therapy group plateaued.

The 10-year OS rate was 6% for the matched-targeted group and 1% for the nonmatched group.

Multivariate analysis showed matched targeted therapy was an independent factor for the prediction of longer OS (P < .001).

The median OS was 9.3 months in the matched therapy group compared with 7.3 months in the nonmatched therapy group. PFS also was longer in the matched therapy group (4 months vs. 2.8 months).

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When considering baseline characteristics, molecular alterations in the PI3K/AKT/mTOR pathway were an independent factor that predicted shorter OS (HR = 1.22; 95% CI, 1.08-1.38) compared with other molecular alterations. Other independent factors for poorer OS included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts and age 60 years or older.

The randomized phase 2 IMPACT study will compare PFS among patients who receive targeted therapy matched to the molecular characteristics of their tumor to patients whose treatment is not selected based on the molecular analysis of their tumor, Tsimberidou said.

The implementation of precision medicine using next-generation sequencing may lead to significantly improved clinical outcomes among patients with cancer.

“I am optimistic within the next few years we will dramatically improve the outcomes for patients with cancer with increasing implementation of precision medicine,” Tsimberidou said. – by Melinda Stevens

Reference:

Tsimberidou AM, et al. Abstract LBA2553. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

 

Disclosures: Tsimberidou reports a consultant/advisory role with Roche and research funding to her institution from Baxter, Bayer, Boston Biomedical, EMD Serono, Foundation Medicine, IMMATICS, Karus Therapeutics, ONYX, Placon and Stem Cells, Inc. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective

    This is the first and largest study that shows matching treatments to genetic mutations in tumors in patients with advanced cancer improves survival. Patients with advanced cancer who underwent molecular profiling and were found to have actionable mutations and treated on the basis of those actionable mutations had significantly improved OS compared with patients treated with conventional chemotherapy.

    Most of these patients received drugs that were either FDA approved or in advanced clinical trials. So, people didnt have to reinvent the wheel to treat these patients. Prior to precision medicine, patients were treated on the basis of what kind of cancer they had, ignoring all the genetic differences. Precision medicine allows us to focus on the genetic aberrations of the tumor, not on the tumor type and not on the growth kinetics of the tumor. As such, this method of molecular profiling tumors and treating on the basis of mutations is the wave of the future.

    Large-scale efforts like IMPACT2 and ASCOs TAPUR will bring these efforts to many more patients and hopefully usher in a new way of treating advanced cancer to improve OS for many more patients.

    • Catherine M. Diefenbach, MD
    • NYU Langone Health ASCO expert

    Disclosures: Disclosure: Diefenbach reports consultant/advisory roles with Bayer, Bristol-Myers Squibb, Genentech/Roche, Merck and Seattle Genetics, as well as research funding from Bristol-Myers Squibb, Genentech, Incyte, LAM Therapeutics, Merck, Millennium and Seattle Genetics.

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