Performing a liquid biopsy of circulating tumor cells may help identify patients who are at risk for node-positive melanoma relapse and identify patients who wish to avoid the toxicities associated with systemic adjuvant therapy, according to the results of a prospective study from The University of Texas MD Anderson Cancer Center, which was recently published in Clinical Cancer Research.
Anthony Lucci, MD
Performing a liquid biopsy of circulating tumor cells (CTCs) may help identify patients who are at risk for node-positive melanoma relapse and identify patients who wish to avoid the toxicities associated with systemic adjuvant therapy, according to the results of a prospective study from The University of Texas MD Anderson Cancer Center, which was recently published inClinical Cancer Research.1
“Our findings are significant, given that there is a need for blood-based biomarkers to guide clinical decision making for stage III melanoma patients,” said Anthony Lucci, MD, professor of breast surgical oncology and surgical oncology, and study lead. “There currently are no blood tests available to help doctors accurately tell which patients are likely to relapse, and should be given therapy, and which are low risk, and could be observed.”
The CTC analysis included 243 patients with a median tumor thickness of 2.3mm. Of these patients, 34% patients had an ulcerated tumor (n = 83), 3% had less than 1 mitotic figures per mm2(n = 8), 14% had up to 2 mitotic figures per mm2(n = 33), 40% had between 3 and 10 mitotic figures per mm2(n = 96), and 20% has more than 10 mitotic figures per mm2. As far as the presence of mutations, 30% of patients haveBRAFV600E-mutant tumors (n = 73). Nineteen percent had stage IIIA disease (n = 45), and 28% had stage IIIB disease (n = 67), 49% were stage IIIC ( n = 118), and 5% were stage IIID (n = 13). One CTC was identified in 37% of patients (range 034), 17% of the patients had two CTCs (n = 41), and 5% had 3 or more CTCs per 7.5 mL of blood. Disease relapse within 6 months of the baseline tumor cell assessment occurred in 14% of patients (n = 33).2
The results from the analysis showed that 8% of patients who had 0 CTCs at baseline relapsed. Additionally, 22.4% of those with 1 CTC, 24.1% with 2 CTCs, and 25% of patients with ≥3 CTCs relapsed. As the number of CTCs increased in these patients, so did the number of release (P= .002). This was not the case in the cohort of patients with non-metastatic disease of whom 17% had more than 2 CTCs and 5% had more than 3 CTCs. Regarding mutation status and disease stage, these were not associated with the presence of CTCs at baseline draw.
Fifty-four percent of patients in the study received adjuvant therapy. Six patients received chemotherapy that included cisplatin, vinblastine, dacarbazine, and taxanes. Targeted therapy was given to 18 patients, which included dabrafenib (Tafinlar), trametinib (Mekinist), vemurafenib (Zelboraf), dasatinib (Sprycel), sorafenib (Nexavar), regorafenib (Stivarga), and sunitinib (Sutent). Fifty-six patients were treated with immunotherapies such as interferon-α (Roferon-A), ipilimumab (Yervoy), nivolumab (Opdivo), pembrolizumab (Keytruda). The remaining 52 patients received other therapies, which included interleukin-2, talimogene laherparepvec (Imlygic), and the GP-100 vaccine.
“Our analysis demonstrated that CTC detection was significantly associated with a decrease in relapse-free survival at 6 months, and persisted at a 54-month longer-term follow-up,” said Lucci. “The data from this study provide support for the future pursuit of liquid biopsy techniques to help identify patients most likely to benefit from adjuvant systemic therapy.”
The study had a few limitations, notably that at the time of patients accrual, extensive tumor molecular profiling was not routinely performed on patients with stage III disease. Additionally, investigators were limited by the availability of effective immunotherapy and targeted therapy regimens and were therefore unable to if the current treatments affect CTC detection and patients outcomes. Because of these limitations, the investigators were not able to determine how tumor mutation or molecular signature related to the presence of CTCs.
The study is ongoing and continues to enroll patients with stage III melanoma in an effort to address the limitation faced during the study. The goal is to show that liquid biopsy had a predictive benefit for these patients.1