Liquid Biopsy Testing Detects Recurrence in High-Risk NSCLC

Chimbu Chinniah

The results of a recent prospective study demonstrate that circulating tumor cells (CTCs) can reveal disease recurrence an average of 6 months prior to conventional imaging in patients with locally advanced non—small cell lung cancer (NSCLC), findings that may help support the use of liquid biopsies to monitor high- risk patients in conjunction with screening.¹

According to Chimbu Chinniah, a research fellow in radiation oncology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and the lead author of the study, this is the largest prospective clinical trial to date of CTCs as biomark- ers for locally advanced NSCLC.

The findings, presented at the 2017 Multidisciplinary Thoracic Cancers Symposium, come amid evidence that lung cancer screening rates in the United States have remained low and unchanged despite recommendations that high- risk current and former smokers be screened, according to findings from a study commissioned by the American Cancer Society published in JAMA Oncology.²

The percentage of eligible smokers who reported low-dose computed tomography (CT) screening rose less than 1 percentage point, from 3.3% in 2010 to 3.9% in 2015. Although 6.8 million smokers were eligible to receive screening in 2015, only 262,700 underwent testing.² Jemal et al identified a lack of awareness about screening among smokers, issues with access to care, and a knowledge gap among physicians as reasons for the low numbers.

The use of liquid biopsies in biomarker screen- ing could be crucial in identifying recurrence of disease in patients with NSCLC. “The additional lead time afforded by an earlier diagnosis may enable doctors to better tailor alternative and salvage treatments to improve their patients’ outcomes and quality of life. Earlier detection of recurrence may even translate into an increased likelihood of curing these patients when their tumor burden is lowest and thus more likely to respond to therapy,” Chinniah said in a statement.

Chinniah and colleagues recruited 48 patients with stage II-III locally advanced NSCLC for the study (Table). Blood samples were obtained before treatment, during treatment (at weeks 2, 4, and 6) and following treatment (at months 1, 3, 6, 12, 18, and 24). CTCs were identified by analyzing the samples with an adenoviral probe that detects elevated activity of telomerase, an enzyme produced when cancer cells replicate.

Table. How the Study Was Conducted¹

“High levels of telomerase are found in almost all cancer cells, but almost no normal cells, with the exception of rare stem cells. Consequently, it’s a specific marker of live cancer cells,” Chinniah explained during a press briefing at the symposium, which the American Society for Radiation Oncology sponsored March 16 to 18 in San Francisco.

Surveillance scans with CT or positron emission tomography(PET)/CT imaging were performed at 3-month intervals. Notably, two-thirds of recur- rent patients showed a rise in CTC counts at an average of 6 months prior to detection with a PET/ CT or CT scan.

At a median follow-up of 10.9 months following treatment, 46% of the patients experienced recurrence or progression, as detected by conventional surveillance scans and biopsies. The median time to recurrence was 7.6 months, with a range of 1.3 to 32 months. Blood samples were obtained following chemoradiation therapy for 20 of the 22 patients who experienced recurrence.

The study concluded that monitoring for CTCs in patients undergoing chemoradiation for locally advanced NSCLC is feasible, even preferable. “Circulating tumor cell elevations in many patients meaningfully precede radiologic evidence of disease recurrence, and may be a promising biomarker of progressive or recurrent disease, which may help guide early salvage therapeutic strategies,” Chinniah said in his presentation. “Assays identifying circulating tumor cells may allow for noninvasive and sequential monitoring of lung cancer.”

More research is needed to test whether the early detection of disease recurrence given by analysis of CTCs translates into improved outcomes. “Liquid [biopsy] in non—small cell lung cancer has not really been explored in that much detail utilizing CTCs and for circulating tumor DNA, that’s been looked at more for metastatic disease. Our study is telomerase-based and is looking at live cells, so we’re looking at what’s in the cell itself, not a cell surface marker. We believe this to be more sensitive and specific than other assays avail- able on the market,” Chinniah said.

Experts say the need for liquid biopsies in NSCLC is particularly pressing, since biopsies often cannot be performed or do not yield enough tissue for molecular testing.

In June 2016, the FDA approved Roche Molecular Systems’ cobas EGFR Mutation Test v2 for the detection of EGFR mutations from plasma samples as a companion diagnostic for patients with metastatic NSCLC who are candidates for therapy with osimertinib (Tagrisso) or erlotinib (Tarceva). This was the first FDA approval of a liquid biopsy test as an aid in oncologic clinical decision making.

Other companies are developing liquid biopsies for potential use in a variety of clinical settings in lung cancer.

References

1. Chinniah C, Aguarin L, Cheng P, et al. Prospective trial of circulating tumor cells as a biomarker for early detection of recurrence in patients with locally advanced non-small cell lung cancer treated with chemoradiation. Abstract presented at: 2017 Multidisciplinary Thoracic Cancers Symposium; March 16-18, 2017; San Francisco, CA. Abstract 4. thoracicsymposium.org/thoracicabstracts17/.
2. Jemal A, Fedewa SA. Lung cancer screening with low-dose computed tomography in the United States—2010 to 2015 [published online February 2, 2017]. JAMA Oncol. doi: 10.1001/jamaoncol.2016.6416.