PracticeUpdate: Haematology & Oncology

CONFERENCE COVERAGE 24

Serial evaluation of plasma circulating tumour DNA can detect molecular response to treatment for metastatic breast cancer S erial evaluation of plasma circulating tu- mour DNA can detect molecular response to treatment for metastatic breast cancer. logistic regression, and a compound symmetric correlation structure was assumed.

The answer to the question we posed, whether the superiority of antibody-based therapy over non- antibody-based therapy aimed

A total of 68.8% of cases were hormone receptor-positive, 18.8% human epidermal receptor 2-positive, and 27.1% triple-negative breast cancer. Treatments received were 58.4% hormonal therapy, 31.2% chemotherapy, 26.4% included anti-human epidermal receptor 2 therapy, two cases were targeted therapy, and one was not receiving treatment. Three patients harboured stage 4 disease in complete remission. Circulating tumour DNA analysis was repeated an average of 4 days prior to radiological evaluation. The average time between repeat assessments was 108.5 days. In 93% of patients, a genomic alteration was detected at some point during their course of disease. The most common mutations detected were TP53 41.7%, PIK3CA 35.4%, ESR1 18.8%, and ERBB2 amplifications 6.3%. A genomic alteration was detected in all 40 patients who harboured untreated newly diagnosed advanced breast cancer or progressive disease at the time of blood draw. A dichotomised change in circulating tumour DNA is a significant predictor of clinical benefit (P < 0.0001). Intrapatient correlation is estimated to be 0.273 for the transformed variable. Themodel yields a predicted probability of clinical benefit of 26.9% when the increase in circulating tumour DNA is ≥ 0.5 and when the increase in circulating tumour DNA is <0.5, the predicted probability of clinical benefit is 78.4%. The concordance of change in circulating tumour DNA and change in cancer antigen 27–29 was 76.2%. Dr Rodriguez said that serial evaluation of plasma circulating tumour DNA can detect molecular response to treatment. This response, in turn, may correlate with clinical benefit and guide treatment decisions. He added, “For decades, molecular response to treatment has been applied in the clinic to accurately monitor effectiveness of treatment and guide treatment decisions in patients with leukaemia, but not in patients with breast cancer.” This test result may aid the physician in determining the frequency of radiographic evaluation. Early indication that a chosen therapy is not effective may help avoid overtreatment in favour of and initiating an alternative regimen. Prospective studies are needed to confirm these results and determine the optimal timing and frequency of testing.

This response, in turn, may correlate with clinical benefit and guide treatment decisions, results of a retrospective, single-centre study show. Angel A. Rodriguez, MD, of Houston Methodist Cancer Center, Houston, Texas, explained that in patients with metastatic breast cancer, no evidence supports changing therapy based on changes in blood biomarker, because it fails to improve outcome. Guidelines suggest that repeating radiographic evaluation every 2 to 6 months depending on the patient and treatment. The clinical benefit of treatment is defined as complete response, objective response, or stable disease as determined by Response Evaluation Criteria in Solid Tumors criteria on radiological evaluation. Serial measurements of blood biomarkers such as CA2729 and circulating tumour cells have proven unsuccessful in predicting clinical benefit. Circulating tumour DNA may be more sensitive and specific and has emerged as a potential biomarker that may predict response to therapy or progression of disease. Dr Rodriguez commented, “Though this technology is intended to discover a target to treat cancer, we could also use it to track and quantify the molecular fingerprint of the disease in the blood.” Dr Rodriguez and coinvestigators wished to determine whether serial monitoring of circulating tumour DNA allele frequency levels predict clinical benefit of a treatment. Fifty-five patients with measurable metastatic breast cancer who underwent serial monitoring of circulating tumour DNA with Guardant360 between 2014 and 2016 were included. Median age was 55.9 (27–94) years. Clinical outcomes were determined per standard guidelines. The analysis was performed on all patients who underwent serial measurement of circulating tumour DNA with no change in therapy between measurements and whose repeat blood draw was within 30 days of repeat radiographic evaluation. The dataset contained 125 observations from 48 unique patients. The relationship between change in circulating tumour DNA and clinical benefit was analysed using a generalised linear model with a random-subject effect to account for intrapatient dependence that resulted from obtaining multiple evaluations from the same patient. A logit link function was used akin to

at HER2 could be predicted by the tumour’s immune status, was yes. But this is only the case for the CD8 marker and not for the eight other factors we examined. >26 We found that PIK3CA mutations could be found in circulating tumour DNA in several patients with either wild type or unknown status in tumour tissue, making liquid biopsies a useful alternative to tumour tissue for detecting these mutations. >30

PracticeUpdate Editorial Team

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY