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IMPACT Trial: Support for Targeted Cancer Tx Approaches

— Survival doubled with therapy matched to tumor genetics

Ƶ MedicalToday

CHICAGO -- Using molecular tumor markers to select targeted therapy slowed cancer growth and doubled survival, according to a retrospective analysis of early experience with precision medicine.

Among 1,300 patients with at least one identified genetic alteration, those treated with a drug that targets the alteration had a 3-year overall survival (OS) of 15% as compared with 7% for patients who received nonmatched therapy. At 10 years, 6% of the patients treated with targeted therapy were still alive versus 1% of those who received conventional therapy, reported Apostolia-Maria Tsimberidou, MD, PhD, of the MD Anderson Cancer Center in Houston.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Progression-free survival, objective response rate, and clinical benefit rate all favored targeted therapy, she reported at the American Society of Clinical Oncology (ASCO) meeting.

"This is the first and largest study -- with the longest follow-up -- to assess the impact of precision medicine on survival across multiple cancer types," she said during an ASCO press briefing. "Our findings show that molecular testing of tumors using next-generation sequencing can be used to optimize therapy and should be taken into consideration when selecting therapy for patients with difficult-t0-treat cancers."

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Apostolia-Maria Tsimberidou, MD, PhD, presenting the results

Noting that the results represented experience with patients treated as long ago as 2007, Tsimberidou said, "I am optimistic that in the next few years, we will dramatically improve outcomes for patients with cancer by increasing implementation of precision medicine."

The advent of precision medicine transformed traditional paradigms for treating cancer, which focused on the type of cancer, growth kinetics, and other less specific methods of matching therapy to disease, said ASCO expert Catherine Diefenbach, MD, of NYU Langone Medical Center in New York City.

"This method of molecular profiling tumors and treating on the basis of actionable mutations is the wave of the future," said Diefenbach. "Large-scale [studies] will bring these efforts to many, many more patients and will usher in new approaches to treating advanced cancer and hopefully improve overall survival."

Tsimberidou reported long-term follow-up data from the Initiative for Molecular Profiling in Advanced Cancer Therapy . Begun in 2007, the study had a working hypothesis that selecting cancer therapy on the basis of patient's tumor molecular analysis would lead to better outcomes as compared with the prevailing standard approaches.

The study involved patients with advanced-stage cancers for which no standard treatment options existed or who had incurable rare cancers. Study participants had been referred for molecular testing of tumor specimens, which might have involved a single gene during early stages of the testing program to as many as 50 in the later years.

If the test results showed an actionable mutation, patients were matched with targeted therapies, if available. If no appropriate targeted agents were available, patients received nonmatched treatment.

From 2007 to 2013, 3,743 patients underwent molecular testing, which revealed at least one targeted alteration in 1,307 patients. Subsequently, 711 of the patients were matched to a targeted therapy, and 596 received nonmatched therapy. The patients had received a median of four prior regimens, and 2.8% of the cohort had no prior treatment before referral for molecular evaluation. The most common types of cancer represented by the cohort were gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%), and lung (8.7%).

Tsimberidou reported that matched therapy resulted in an objective response rate of 16.2% versus 5.2% for nonmatched treatment. Additionally, 18.4% of matched patients and 14.7% of unmatched patients had stable disease for at least 6 months. Matched patients had a significantly higher clinical benefit rate (response plus stable disease: 34.9% versus 20.1%, P<0.001).

Patients who were matched to therapy had a median PFS of 4.0 months and median OS of 9.3 months, as compared with 2.8 and 7.3 months, respectively, for the unmatched population (HR 0.67, HR 0.72, P<0.001). By multivariate analysis, receiving nonmatched therapy was an independent predictor of worse survival (HR 1.30, 95% CI 1.16 to 1.46, P<0.001). Alterations in the PI3K/AKT/mTOR pathway also were associated with worse survival (HR 1.25, 95% CI 1.10 to 1.42, P<0.001).

Investigation of the IMPACT strategy will continue in IMPACT 2, an ongoing prospective, phase II randomized trial comparing PFS in patients who received targeted therapy matched to tumor molecular characteristics versus treatment versus nonmatched therapy.

Although IMPACT and other studies have demonstrated the potential benefits of precision medicine and analysis of tumor genetics, the oncology community still has a lot to learn, cautioned Richard Schilsky, MD, ASCO chief medical officer.

"There's a lot of this going on in routine clinical practice these days, and that's probably a leap a little too far ahead of what the data will support, at least in the context of patients with far-advanced cancer," he said. "Doing this in the context of a research program is a completely valid and important thing to do until we get the information we need about the circumstances under which these approaches actually work."

Otis Brawley, MD, American Cancer Society chief medical officer, offered a more succinct cautionary assessment. "Precision medicine has given us some things, but it has promised a lot -- which it has yet to deliver," he said.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined Ƶ in 2007.

Disclosures

Tsimberidou disclosed relevant relationships with Baxter, Bayer, Boston Biomedical, EMD Serono, Foundation Medicine, IMMATICS, Karus Therapeutics, ONYX, Placon, and Stem Cells Inc. Co-authors disclosed multiple relevant relationships with industry.

Primary Source

American Society of Clinical Oncology

Tsimberidou AM, et al "Precision medicine: Clinical outcomes including long-term survival according to the pathway targeted and treatment period: The IMPACT study" ASCO 2018; Abstract LBA2553.