In-House or Centralized Testing? Debating Whether Genomic Sequencing Is Best Conducted at Home

Foundation also has the only US Food and Drug Administration-validated test, so the quality is assured across time and tests, which is not always true of in-house analyses, Dr Alexander said. Although in-house testing may seem less expensive, he added, it’s easy to forget about the cost of buying the machine and keeping the lights on.

Dr Alexander acknowledged that Foundation’s turnaround time can be an issue for some patients. “We’re constantly working on turnaround time,” he said, adding that the company now has labs at its Cambridge, Massachusetts, headquarters, as well as in North Carolina, Germany, and with partners in China. “We’re looking to expand the lab presence,” he stated.

Tests are cheaper to run when they’re batched, which might mean that it takes just as long or longer to get results from an in-house analysis, he noted.

Guardant Health is hoping to change the game by offering liquid biopsies. A study published last fall in JAMA Oncology showed that adding a liquid biopsy for patients with advanced non-small cell lung cancer expanded the detection of targetable mutations and improved delivery of targeted therapies.²

“Regardless of in-house or send-out, liquid biopsy is something that we obviously see as improving that access to genotyping information and precision medicine,” said Justin Odegaard, MD, PhD, Guardant vice president of clinical development. Because of high volume, Guardant can provide a 1-week turnaround for liquid biopsy results, he said.

In a Guardant-sponsored study presented³ at AACR and recently published,⁴ “liquid not only provided more answers for more patients, but also did so faster than tissue genotyping,” Dr Odegaard says. Liquid biopsies can also be effective at determining tumor mutational burden, a different AACR presentation⁵ showed.

Dr Odegaard said Guardant considered selling its liquid biopsy tests to individual labs and allowing them to perform the assays independently, but the technology is complicated, so it made more sense to keep the analysis centralized. “It’s something that’s very difficult to put in a box, slap on a label, and ship it out,” he said. Guardant, which is pursuing FDA approval for its Guardant360 and GuardantOMNI tests, has partnered with The University of Texas MD Anderson Cancer Center, Houston, to develop a specific test for them, and is exploring initiatives with other institutions, as well, he said.

Still, Dr Hofman, the French lung cancer specialist, thinks there are benefits to keeping such testing close to both patient and doctor.

Dr Hofman said it costs him about $2,000 per sample to send a patient’s tissue out for analysis — and that he can do the same analysis in-house for about $600. The in-house process takes time and effort to ensure quality results, Dr Hofman admitted, but he believes it is a viable approach for many institutions.

Keeping the test in-house also means access to the raw data, Dr Hofman says. In his recent comparison of Foundation Medicine’s test with an assay that could be used in-house, 22% of the lung cancer tissue samples and 8% of the melanoma samples didn’t meet Foundation’s stringent standards and couldn’t be analyzed. Dr Hofman said that when he gets back such a result, he can’t always be sure whether it was because of a poor-quality sample, problems during the analysis, or a truly negative result. There’s also an added risk of contamination every time the tissue is packaged and enters a new facility, he noted.

He said he’s also unsure what the companies do with his patients’ DNA after the analysis:  whether they throw it out or use it for their own purposes. “I think it’s more secure for the patient,” to keep it in the treating institution’s own biobank, he said. “We don’t know what they’re doing with our samples.”

References

1. Heeke S, Benzaquen J, Long-Mira E, et al. Comparison of tumor mutational burden using the Ion Oncomine™ TML and FoundationOne™ assays with routine clinical FFPE tissue samples to predict durable clinical benefit in lung cancer and melanoma patients – a multivariate analysis integrating PD-L1 and CD8+ evaluation. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3; Atlanta, Georgia. Abstract 4889/12.
2. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173–180.
3. Leigh NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC). Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3; Atlanta, Georgia. Abstract 4460.
4. Leigh NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-0624
5. Peters S, Cho BC, Reinmuth N, et al. Tumor mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a phase 3 study of first-line durvalumab ± tremelimumab vs chemotherapy. Clinical trials plenary session 3: optimizing PD-1/PD-L1 immune checkpoint inhibitor therapy: dedicated to the memory of Waun Ki Hong. Streamed live on April 1, 2019 from the American Association for Cancer Research (AACR) Annual Meeting 2019. Accessed May 14, 2019.