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Integrative genomic profiling helps manage advanced solid tumors

JAMA Oncology
Reuters Health - 04/03/2021 - Next-generation sequencing (NGS) is effective in identifying clinically actionable genomic targets in patients with advanced solid tumors, according to new research.

"We believe the results of our study support a recommendation for directed genetic testing in all patients with advanced cancer, as unanticipated genetic variants with therapeutic relevance are identified, resulting in significant improvement in patient outcomes with potential health benefit for their affected family members," Dr. Arul M. Chinnaiyan of the University of Michigan, in Ann Arbor, told Reuters Health by email.

Studies of comprehensive NGS testing in patients with advanced cancer show a wide range of clinically actionable genomic alterations per patient, Dr. Chinnaiyan and colleagues note in JAMA Oncology. But in many studies, a minority of patients receives therapy informed by sequencing, they add, "making it challenging to assess the degree of clinical benefit gained."

The researchers studied data collected between 2011 and 2018 on 1,015 patients who successfully underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA as well as tumor RNA sequencing. Their mean age was 58 years.

Potentially clinically actionable genomic alterations were discovered in four out of five patients (81%). In all, 132 patients (16%) got sequencing-directed therapy, and of these 49 (37%) showed apparent clinical benefit.

Moreover, 19% of the latter group had an "exceptional" response. And, say the researchers, "None of these therapies would have been recommended per standard of care guidelines, indicating that sequencing information was of significant value."

In particular, in 28 of 55 patients with carcinoma of unknown primary origin, the approach identified the primary site. Subsequent sequencing-directed therapy in 13 of these patients gave clinical benefit in seven, and five showed exceptional responses.

Thus, concluded Dr. Chinnaiyan, as well as being of general use in patients with advanced cancer "our results indicate that patients with rare cancers, particularly those with cancer of unknown primary origin, derive significant clinical benefit from genomic profiling, supporting a recommendation to incorporate this testing into standard-of-care management for these disease entities."

Dr. Timothy A. Yap, co-author of an accompanying editorial, told Reuters Health by email, "The investigators report data that support directed germline testing for inherited cancer predisposition in patients with advanced cancers and the use of integrative genomic profiling as a component of standard of care for patients."

"It is evident that such integrated precision medicine strategies are potentially beneficial in cancers without clear treatment options, such as cancer of unknown primary and other rare tumors," added Dr. Yap of The University of Texas MD Anderson Cancer Center, in Houston. "Such efforts will allow us to deliver personalized therapies with potential therapeutic benefit to patients and to further refine the development of precision medicine efforts in oncology."

SOURCE: https://bit.ly/3rc5N77 and https://bit.ly/30kiMrH JAMA Oncology, online February 25, 2021.

By David Douglas

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