Switching Chemotherapy Based on Elevated Circulating Tumor Cells Does Not Change Outcome in Metastatic Breast Cancer


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Jeffrey B. Smerage, MD, PhD

San Antonio Breast Cancer Symposium: C Kent Osborne, MD, presented the William L. McGuire Memorial Lecture award to Monica Morrow, MD, FACS. Dr. Morrow is Chief, Breast Service, Department of Surgery, and Anne Burnett Windfohr Chair of Clinical Oncology, at Memorial Sloan Kettering Cancer Center in New York. Dr. Morrow delivered the William l. McGuire Memorial Lecture on “Local Therapy in the Molecular Era: Relevant or Relic?” Photo Courtesy © SABCS/Todd Buchanan 2013.

These smaller studies may help us identify patients who will benefit from hormonal therapy, as well as to select the next therapy for nonresponders.

Jeffrey B. Smerage, MD, PhD

Elevated circulating tumor cells were prognostic for survival but did not pan out as a marker for switching after one cycle of chemotherapy in patients with metastatic breast cancer. The phase III Southwest Oncology Group (SWOG) S0500 clinical trial, presented at the 2013 San Antonio Breast Cancer Symposium, showed that switching chemotherapy after one cycle based on elevated circulating tumor cell levels did not improve progression-free survival or overall survival in women with metastatic breast cancer.1

“We concluded that [circulating tumor cells] are not a good marker to help decide whether to switch chemotherapies early after only one cycle of initial therapy,” said Jeffrey B. Smerage, MD, PhD, Clinical Associate Professor in Medical Oncology at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

“Our hope was that switching would increase the chances of having an effective therapy and decrease exposure to toxicity from less effective therapies, and that early switching based on [circulating tumor cells] would improve survival and time to progression,” he continued.

“Most important, we have validated the hypothesis that the group of patients with elevated [circulating tumor cells] at baseline and 21 days after starting the first chemotherapy has a worse prognosis with regard to [progression-free and overall survival], while low baseline levels signal a very good prognosis,” he told listeners.

Study Design

SWOG S0500 recruited 624 patients with measurable metastatic disease between 2006 and 2012. Circulating tumor cells were captured and enumerated using the CellSearch System, one of several platforms designed for this purpose, and the only one that is U.S. Food and Drug Administration–approved for determining prognosis and monitoring therapy.

Of the 595 patients eligible for the trial, 276 had low circulating tumor cells at baseline and went on Arm A continuing on their initial chemotherapy. Among 319 patients with elevated circulating tumor cells at baseline, 286 had a circulating tumor cell result at day 21 after the first cycle of chemotherapy. Of these, 163 had decreased levels of circulating tumor cells at day 21 and were continued on their initial chemotherapy (arm B); 123 patients with elevated circulating tumor cells at day 21 were randomly assigned to arm C1 and continued initial chemotherapy (n = 64) or were randomly assigned to arm C2 and had a switch in chemotherapy (n = 59 patients).

Dr. Smerage noted that the study was not designed to compare chemotherapies.

Key Results

Median overall survival was 12 months for both randomized arms (maintaining therapy and switching therapy based on circulating tumor cell levels). Median progression-free survival was 3.5 months for the maintain-therapy arm and 4.6 months for the switch-therapy arm, which was not statistically
significant.

Low baseline circulating tumor cell levels (defined as < 5 cells/7.5 mL) were associated with a very good prognosis, with median overall survival of 35 months in arm A (patients with low circulating tumor cell levels at baseline. Elevated circulating tumor cells at baseline that drop below the threshold after one cycle of chemotherapy were associated with median overall survival of 23 months (arm B). Patients with elevated circulating tumor cells after one cycle of chemotherapy (arms C1 and C2) had the worst prognosis.

“Although chemotherapy may be effective in some patients [with elevated circulating tumor cells], it does not have a prolonged effect. Our results suggest that this patient population needs more effective treatment options beyond chemotherapy,” he commented. “Early consideration of clinical trial participation would be appropriate.”

At the time the study was initiated, the technology only allowed enumeration of circulating tumor cells. “Now we can do more with molecular profiling of [circulating tumor cells], and we hope this will lead to the ability to predict appropriate treatment strategies for patients that simply counting cells does not allow us to do,” Dr. Smerage said.

Ongoing circulating tumor cell studies at the University of Michigan include a three-center study of HER2 cells and circulating tumor cells to predict which patients have high-risk disease without requiring more biopsies. Another study will test estrogen signaling in circulating tumor cells prior to initiation of hormonal therapy and then on treatment to determine if these markers predict better outcomes.

“These smaller studies may help us identify patients who will benefit from hormonal therapy, as well as to select the next therapy for nonresponders. Once we have positive results in smaller studies, we will move to larger ones,” Dr. Smerage told listeners. ■

Disclosure: Dr. Smerage has received research funding from Genomic Health.

Reference

1. Smerage JB, Barlow WE, Hortobagyi GN, et al: SWOG S0500: A randomized phase III trial to test the strategy of changing therapy versus maintaining therapy for metastatic breast cancer patients who have elevated circulating tumor cell (CTC) levels at first follow-up assessment. 2013 San Antonio Breast Cancer Symposium. Abstract S5-07. Presented December 13, 2014.


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