IMPACT study: Matched targeted therapy improves survival in advanced cancer

 

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

 

“We [also] wanted to see if adding the intervention ... would hold significance in this multivariate model, and we found that ... nonmatched therapy was associated with adverse survival; it was an independent factor associated with worse survival,” she said. “Therefore, matched targeted therapy is associated with longer survival.”

In the randomized, phase 2 trial IMPACT 2, progression-free survival will be compared in patients with and without matched targeted therapy, and the prognostic scoring system developed as part of IMPACT to predict overall survival based on baseline characteristics will be further evaluated, she said.

During a discussion of the findings during the press briefing, ASCO Expert Catherine M. Diefenbach, MD, said the type of precision medicine studied in IMPACT is “the wave of the future.

“Large scale efforts such as ASCO’s TAPUR or the NCI-MATCH trial will bring these efforts to many, many more patients, and hopefully usher in a new way of treating advanced cancer patients that will improve overall survival for many more patients,” said Dr. Diefenbach, of New York University.

Dr. Tsimberidou reported a consulting or advisory role with Roche, as well as research funding to her institution from EMD Serono, Baxter, Foundation Medicine, ONYX, Bayer, Boston Biomedical, Placon, IMMATICS, Karus Therapeutics, and StemCells.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

 

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

 

“We [also] wanted to see if adding the intervention ... would hold significance in this multivariate model, and we found that ... nonmatched therapy was associated with adverse survival; it was an independent factor associated with worse survival,” she said. “Therefore, matched targeted therapy is associated with longer survival.”

In the randomized, phase 2 trial IMPACT 2, progression-free survival will be compared in patients with and without matched targeted therapy, and the prognostic scoring system developed as part of IMPACT to predict overall survival based on baseline characteristics will be further evaluated, she said.

During a discussion of the findings during the press briefing, ASCO Expert Catherine M. Diefenbach, MD, said the type of precision medicine studied in IMPACT is “the wave of the future.

“Large scale efforts such as ASCO’s TAPUR or the NCI-MATCH trial will bring these efforts to many, many more patients, and hopefully usher in a new way of treating advanced cancer patients that will improve overall survival for many more patients,” said Dr. Diefenbach, of New York University.

Dr. Tsimberidou reported a consulting or advisory role with Roche, as well as research funding to her institution from EMD Serono, Baxter, Foundation Medicine, ONYX, Bayer, Boston Biomedical, Placon, IMMATICS, Karus Therapeutics, and StemCells.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

 

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

 

“We [also] wanted to see if adding the intervention ... would hold significance in this multivariate model, and we found that ... nonmatched therapy was associated with adverse survival; it was an independent factor associated with worse survival,” she said. “Therefore, matched targeted therapy is associated with longer survival.”

In the randomized, phase 2 trial IMPACT 2, progression-free survival will be compared in patients with and without matched targeted therapy, and the prognostic scoring system developed as part of IMPACT to predict overall survival based on baseline characteristics will be further evaluated, she said.

During a discussion of the findings during the press briefing, ASCO Expert Catherine M. Diefenbach, MD, said the type of precision medicine studied in IMPACT is “the wave of the future.

“Large scale efforts such as ASCO’s TAPUR or the NCI-MATCH trial will bring these efforts to many, many more patients, and hopefully usher in a new way of treating advanced cancer patients that will improve overall survival for many more patients,” said Dr. Diefenbach, of New York University.

Dr. Tsimberidou reported a consulting or advisory role with Roche, as well as research funding to her institution from EMD Serono, Baxter, Foundation Medicine, ONYX, Bayer, Boston Biomedical, Placon, IMMATICS, Karus Therapeutics, and StemCells.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.