Consider Conducting Genomic Evaluations Earlier When Advanced Cancer Is Involved, Study Suggests

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Molecular profiling is more often used after standard cancer treatments have failed; a recent study suggests that it could effectively guide first-line treatment, especially for cancers with a poor prognosis.

Conducting genomic evaluations of advanced malignancies can be effective in guiding first-line treatment instead of waiting until standard-of-care therapies have failed, according to a recent study.

Writing in Genome Medicine, researchers hypothesized that developing matched, individualized combination therapies for patients with advanced cancers who had not been previously treated might be feasible and effective.

Just under 150 adults with newly diagnosed cases of advance malignancies were enrolled in the prospective study at 2 sites: Moores Cancer Center and Avera Cancer Institute in Sioux Falls, South Dakota. The patients had either incurable, lethal cancers (at least a 50% cancer-associated mortality rate within 2 years) or they had a rare tumor with no approved therapies.

Researchers performed extensive genomic profiling of all patients, identifying and documenting all detectable gene mutations to create a molecular profile of each patient’s tumor that would guide their precision cancer therapy.


“Each patient received a personalized N-of-1 treatment plan that optimally matched therapeutic agents to their tumor’s distinct biology, while also taking into account other variables, such as underlying conditions or co-morbidities unique to that patient,” said first author Jason Sicklick, MD, professor of surgery at UC San Diego School of Medicine and surgical oncologist at Moores Cancer Center, in a statement.

Of the 145 patients, 76 received personalized treatment based on their molecular profile, using a host of therapeutic approaches, from immunotherapies to targeted agents to traditional chemotherapeutic agents that were matched to their tumor’s genomic profile. Sixty-nine patients could not be treated due to a variety of reasons, including inadequate organ function, clinical deterioration and death during the study period.

For the 76 patients who received precision cancer therapy, the median overall survival rate was 6.9 months compared to 3 months for patients who were not treated.

“This speaks to the aggressive biology of these cancers as many of these patients did not even receive standard of care treatment as opposed to a failure of a precision medicine approach,” said the authors. “Failure of molecular profiling (tissue and blood) affected only three (2 percent) of consented patients, suggesting it was feasible to perform molecular profiling in 98 percent of patients.”

The findings, concluded the researchers, affirm the tenets of precision-personalized medicine, the benefits of targeting multiple drivers of disease rather than single causes.

“It also shows that it is feasible to move this approach earlier in the treatment process of lethal malignancies, with the objective of improving outcomes before resistance mutations accumulate,” they wrote.


Sicklick JK, Kato S, Okamura R, et al. Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-naïve study. Genome Med. Published online October 4, 2021. doi: 0.1186/s13073-021-00969-w