Serial Circulating Tumor Cell Enumeration Predicts OS in Metastatic Breast Cancer

Wolfgang Janni, MD, PhD

Follow-up circulating tumor cell (CTC) assessments were confirmed to strongly predict overall survival (OS) outcomes in patients with metastatic breast cancer, when performed at a median of 29 days following treatment initiation, according to data from a large pooled analysis presented during the 2020 San Antonio Breast Cancer Symposium.¹

Results showed that the median OS for patients who were persistently CTC negative, meaning they had negative status at baseline and at the time of follow-up, was 47.05 months compared with 17.87 months in patients referred to as persistently positive for CTC (HR, 3.15; 95% CI, 2.78-3.57; P < .0001).

Moreover, CTC responders and the patients who were CTC positive at baseline but had CTC negativity at follow-up were found to have a significantly better OS compared with CTC nonresponders, with a HR of 0.49 (95% CI, 0.44-0.54; P <.0001).

“These results provide clinical validation of CTC monitoring as an early treatment response marker in advanced breast cancer and suggest the potential for clinical utility,” Wolfgang Janni, MD, PhD, professor and chair of the Department of Obstetrics and Gynecology at the University of Hospital Ulm, Germany, said during a press briefing ahead of the meeting.

Many studies have suggested the clinical relevance of using CTC monitoring as a way to evaluate response status in patients with metastatic breast cancer. In the study presented during the briefing, investigators sought to perform a comprehensive pooled analysis of global data to better define and understand the effectiveness of serial CTC enumeration as an early treatment monitoring tool for patients with metastatic disease.

“The focus [of this research] is on the predictive power of CTCs for OS in different breast cancer subtypes,” noted Janni.

To do this, investigators screened peer-reviewed publications with data on serial CTC assessment, which included both baseline and at least 1 follow-up sampling in patients with advanced breast cancer. Only trials that utilized the CellSearch Circulating Tumor Cell test were included, as this is the first and only clinically validated, system that has received FDA clearance for the identification, isolation, and enumeration of CTCs.²

“Investigators were then asked to provide individual patient data for this pooled analysis,” said Janni. All data for which at least 1 baseline and 1 follow-up CTC assessment was done, were included, leading to a dataset comprised of a total of 4079 individual patient records.

Records came from the CALGB 40502 (ALLIANCE) trial (11.2%; n = 455), CALGB-40503 (ALLIANCE; 5.7%; n = 231), COMET (5.4%; n = 222), DETECT (6.7%; n = 273), IMMC-01 (4.6%; n = 189), N1031 (0.7%; n = 30), NSABP B-06 (1.7%; n = 71), SWOG 0500 (6.9%; n = 280), TBCRC 001 (2.1%; n = 84), European pooled analysis (EPAC, which included updated data sets; 26.0%; n = 1060), MDACC institutional study (9.5%; n = 387), multicenter Chinese study (5.4%; n = 220), multicenter Japanese study (2.6%; n = 106), and single institutional data (11.5%; n = 471).

To examine the role of serial CTC enumeration as a tool for early treatment monitoring, investigators categorized patients by CTC status at baseline and follow-up in 4 groups: CTC negative/negative, or the persistently negative group (19.9%); CTC negative/positive (7.5%), CTC positive/negative (27.1%), and CTC positive/positive, or the persistently positive group (45.5%).

“Please note here, and in all of the following slides, that the cutoff for CTC positivity used is at least 1 CTC,” added Janni.

Additional results showed that the median OS in the CTC negative/positive group was 29.67 months (HR, 1.74; 95% CI, 1.43-2.10; P <. 0001), while the median OS in the CTC positive/negative group was 32.20 months (HR, 1.52; 95% CI, 1.32-1.74; P <.0001). “The median OS and HRs from these 2 groups did not different significantly,” noted Janni.

When investigators then went on to summarize the HRs of CTC responders in all 3 disease subtypes to provide clear evidence of improved OS in responders compared with nonresponders, added Janni. In patients with luminal-like disease, the HR was 0.47 (95% CI, 0.41-0.54) vs 0.54 (95% CI, 0.42-0.69) in those with HER2-type disease, vs 0.41 (95% CI, 0.32-0.52) in those with triple-negative disease.

“This is a very large pooled analysis that really instructs us on a noninvasive approach that may provide an advantage over conventional imaging methods that can take up to 3 months before changes can be detected in breast tumor tissue,” concluded moderator Carlos Arteaga, MD, FAACR, AACR past president, fellow of the AACR Academy, director of the Simmons Comprehensive Cancer Center, and Lisa K. Simmons Distinguished Chair in Comprehensive Oncology at the UT Southwestern Medical Center, in the press briefing.

References

1. Janni W, Yab C, Hayes DF, et al. Clinical utility of serial circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) – a global pooled analysis with individual patient data. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; virtual. Abstract GS4-08.
2. Platform overview. CellSearch Circulating Tumor Cell Test website. Accessed December 8, 2020. https://bit.ly/33YhHrI.