What is Comprehensive Genomic Profiling and is it the Right Solution for You?

By simultaneously assessing a broad range of biomarkers in one test, CGP identifies clinically actionable alterations to help select the most appropriate targeted therapies and immunotherapies tailored to each patient.  Large CGP panels, especially those covering more than 500 genes, increase the chances of finding guideline-based actionable biomarkers and are ideal for determining patient eligibility into clinical trials. This is important because patients treated with biomarker-guided targeted therapies or immunotherapies show significant improvement in overall survival versus chemotherapy across tumor types.¹ 

While small panel testing focuses on a limited number of genes, CGP provides a more broad and comprehensive genomic landscape of the tumor to maximize the potential therapeutics options for each patient. As treatments options become more sophisticated, understanding what the underlying molecular alterations mean for potential treatments and subsequent treatments will help to advance precision medicine forward.

Scenarios where CGP is preferred over small panel testing

Refractory or second-line (2L) and beyond cancers: In cases where patients did not respond to standard therapies or had exhausted their therapeutic options, CGP can help identify new therapeutic targets or clinical trial options.

Cancers of unknown primary (CUP): CGP can provide clues that may lead to a more accurate diagnosis, potentially leading to a re-evaluation of the tumor type, while simultaneously identifying actionable alterations that smaller panels may have missed.

Cancers where genomic signatures may be insightful: For instance, HRD is important in identifying ovarian cancer patients who may benefit from PARP inhibitors. Additionally, MSI and TMB status can provide insights into cancers more likely to respond to immunotherapy where appropriate.

Clinical trial eligibility: Patients who are potential candidates for clinical trials may benefit from CGP, as it increases the chances of identifying relevant biomarkers required for trial enrollment.

CGP results are key in guiding effective treatment decisions, but in the real-world setting, challenges exist especially when working with small tissue samples often seen with biopsies. When a tumor biopsy is limited in surface area or tumor content, sequencing results cannot be reliably generated due to samples being considered quantity not sufficient or QNS.  Failure rates of 18.4% across solid tumors and even up to 23% in non-small cell lung cancer (NSCLC), where small biopsy specimens are common, have been reported with hybrid-capture based CGP tests.²

As the need grows for processing smaller samples, amplicon-based CGP tests have shown to be highly robust with overall sequencing success rates of 97.1%, despite working with a large proportion of cytological specimens and samples with low inputs (<20 ng).³ In a real-world clinical scenario, a sizeable fraction of samples would have tissue that is insufficient for traditional hybrid-capture based CGP tests.⁴ With an amplicon-based CGP test, small samples, down to 1.89 ng DNA, have been shown to hold exceptionally important clinical information for efficacious therapy selection and enrollment into clinical trials without necessitating another risky biopsy procedure.⁴ 

Compared with conventional tests, CGP uses less tissue and shortens the turnaround time by assessing a broad range of biomarkers at the same time. However, timely CGP is still a major concern, especially with send-out services taking up to 12 days from receipt, that is, if that sample meets certain requirements.⁵

In a real-world study with 2,694 NSCLC patients, timely CGP, meaning CGP results were available before first-line (1L) decisions, increased matched targeted therapy use by 14 percentage points (17% with CGP vs 2.8% without) and precision immune checkpoint inhibitor use by 14 percentage points (18% with CGP vs 3.9% without).⁶ Further, among ALK/EGFR/RET/ROS1-positive patients (n=426), timely CGP increased use of matched targeted therapies by 52 percentage points (76% with CGP vs 24% without), while simultaneously decreasing ineffective and costly immunotherapy use by 31 percentage points (12% with CGP vs 43% without).⁶

Overall, timely CGP result availability before 1L initiation was associated with a 28 percentage point increase in precision therapy use (35% timely CGP vs 6.7% delayed) and a 35 percentage point decrease in empiric therapy use (55% timely CGP vs 90% delayed).⁶ Despite this, nearly half of the patients received CGP results after 1L initiation, of which 11% would have had a targetable driver alteration with an approved 1L therapy and an additional 16% would have had a 2L or off-label therapy option.⁶ This speaks volumes to why rapid CGP is absolutely critical, considering the potentially missed opportunities in improving patient care.

As cancer care has shifted from an empiric-based approach to now, a precision-based approach, the case for the use of CGP is strengthening to improve patient outcomes and quality of life. We are witnessing an exciting time in the fight against cancer as more therapies become available and as technological advances make genomic profiling faster, more sensitive, and more affordable. CGP allows us to deliver precision cancer care by elucidating the oncogenic drivers to find the right treatment for the right patient at the right time. In addition, the wealth of data accumulated from CGP can inform future cancer research to help identify new biomarkers for the development of novel and efficacious therapies.

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