Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers


19 of 44 patients treated with genomically guided therapy attained a PFS ratio 1.3 vs. 3 of 57 treated with non-genomically guided therapy.

Similarly, overall PFS ratios were higher for patients with genomically guided therapy vs non-genomically guided therapy.

Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.

Dr. Bryan P. Schneider from the Indiana University Health Precision Genomics Program and the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis, IN, USA said, "Precision medicine approaches that seek to match genomic aberrations to potential treatment avenues are rapidly reshaping treatment for cancer patients."

Figure 1: CONSORT diagram of evaluable population.

Figure 1: CONSORT diagram of evaluable population.

In patients with advanced cancer where treatment options are limited, genomic sequencing is frequently being used to identify targets which are potentially clinically actionable with FDA approved drugs or clinical trials.

In many cases, these targets would have been overlooked under standard clinical practice due to the rarity or novelty of the target, or its presence in a cancer lineage not normally associated with the target.

While several publications to date have determined that many cancers have targetable pathways that may benefit from a precision medicine approach, formal assessment of clinical benefit of these approaches has been lacking.

Published case reports demonstrating exceptional responses to targeted therapy explained by key genomic mutations have brought promise to the field, but analyses of larger cohorts and randomized controlled clinical trials are still needed to help solidify the utility of cancer genomics in clinical practice.

Reported early experience with identifying molecular targets in patients tumors to direct treatment and also performed a formal analysis of clinical benefit by calculating the ratio of the PFS of the patients genomically-guided therapy divided by the PFS of their prior line of therapy.

The Schneider Research Team concluded, "In our cohort of patients, we found a significant improvement in PFS ratio regardless of cut-point and an improvement in median PFS for the genomically directed group. These findings are congruent with those reported to date and support the evolving body of literature that demonstrates superior outcomes for patients who receive genomically guided therapy [23-25]. Moving forward, programs like ASCO's Targeted Agent and Profiling Utilization Registry (TAPUR) study (http://www.tapur.org) will likely facilitate the speed with which the cancer genomics community is able to determine those target/drug combinations with the most utility and simultaneously those that will be futile. Further, the complex interaction between successful target/drug combination and site of disease can be further elucidated with combined data from multiple collaborating groups. Given the emerging body of consistent data demonstrating similar relative benefits to those patients who have access to targeted sequencing, this should be discussed with appropriate patients as a therapeutic avenue."

Full text - https://doi.org/10.18632/oncotarget.10606

Correspondence to - Bryan P. Schneider- [email protected]

Keywords - precision medicine, personalized medicine, genomics, next-generation sequencing

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