Molecular Profiling to ID Targeted Therapies Prolongs Patient Survival

Genetic sequencing of tumors to identify targeted therapy options appears to delay tumor progression and prolong patient survival.

Genetic sequencing of tumors to identify targeted therapy options appears to delay tumor progression and prolong patient survival, according to a retrospective exploratory analysis (abstract LBA2553) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

“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-to-treat cancers,” said lead study author Apostolia Maria Tsimberidou, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first and largest study-with the longest follow-up-to assess the impact of precision medicine approaches on survival across multiple cancer types,” Tsimberidou noted.

Implementation of precision oncology requires a “complete understanding” of tumor biology, including gene pathways and immune system factors that drive tumorigenesis, Tsimberidou said.

The authors analyzed data from 3,743 patients referred to molecular testing services at Clinical Laboratory Improvement Amendments–certified laboratories as part of their participation in the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) clinical trial from 2007 to 2013. The number of genes tested varied between 1 and 50 during the study period. Twenty-four percent of patients had gastrointestinal cancers, 19% had gynecologic malignancies, 13.5% had breast cancer, 11.9% had melanoma, and 8.7% had lung cancer.

A total of 1,307 patients had at least one genetic alteration, 711 (54%) of whom received a targeted therapy based on their test results, and 596 (45.6%) of whom received therapy not matched to their tumor genetics.

Patients who were matched to a targeted therapy had a 3-year overall survival (OS) rate of 15% compared with 7% among patients who did not receive molecular testing–based treatment. The 10-year OS rate was 6% and 1%, respectively (hazard ratio, 0.72; P < .001). In a multivariate analysis, not receiving tumor gene–matched therapy, liver metastases, elevated lactate dehydrogenase levels, low albumin levels, elevated platelets, poor functional status, and patient age over 60 years were each significantly associated with poorer OS.

“Matched therapy was an independent factor predicting longer survival in multivariate analysis,” Tsimberidou said. “PI3K/AKT/mTOR pathway abnormalities were associated with inferior outcomes compared to other alterations.” The research team has developed a prognostic score for OS using that insight. The follow-up randomized phase II IMPACT 2 trial is ongoing.

“It’s been 20 years since the first targeted therapy was introduced,” commented ASCO Expert Catherine Diefenbach, MD, of the NYU Langone Medical Center in New York. “These first ‘precision-medicine’ therapies revolutionized cancer care and helped many patients live longer. But we’ve just scratched the surface. Now with faster and more robust genetic tests, we can help even more patients by treating the cancer based on its genetic makeup rather than solely on its location in the body.”