Enzalutamide in castration-sensitive prostate cancer and ctDNA to monitor early colorectal cancer


In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).

ARCHES trial

Dr. Alan P. Lyss, an oncologist who practices in St. Louis

Dr. Alan P. Lyss

The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.

Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.

ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.

Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.

What this means in practice

It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.

It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.

ctDNA in early colorectal cancer

In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.

The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.

Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.

Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.

What this means in practice

The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.

Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

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