Evidence Indicates That Active Monitoring Is a Viable Alternative to Maintenance Therapy in Stable or Responding Metastatic CRC


Investigators believe that active monitoring presents an alternative option to capecitabine maintenance therapy for patients with stable or responding metastatic colorectal cancer.

Treatment breaks were further supported as an alternative management option for patients who are stable or responding to first-line therapy for metastatic colorectal cancer (mCRC), according to results from the randomized FOCUS4-N trial published in the Journal of Clinical Oncology.

Progression-free survival (PFS) events were observed in 122 of 127 patients in the active monitoring arm compared with 117 of 127 patients in the capecitabine arm. The median PFS was 3.88 months (95% CI, 3.65-4.37) in the capecitabine arm and 1.87 months (95% CI, 1.81-2.14) in the active monitoring arm, respectively. The unadjusted HR was 0.44 (95% CI, 0.33-0.57; P <.0001) and the adjusted HR was 0.40 (95% CI, 0.21-0.75; P <.0001).

“Choices on how to proceed with palliative treatment, in the large majority of patients with incurable mCRC, with stable or responding disease after 16 weeks of first-line therapy need careful consideration with the patient at the core,” the investigators wrote. “Discussions must be informed by the impact of receiving systemic anticancer therapy over the preceding period.”

Trial registration eligibility required patients to be aged 18 years or older with newly diagnosed locally advanced or mCRC whose tumors remained stable or responded to treatment according to a 16-week CT scan. Other eligibility criteria included a randomly assigned CT scan at baseline within 4 weeks of randomization, at least 3 weeks between final chemotherapy or biologic therapy dose and first capecitabine dose, adequate renal and liver function, and a WHO performance status of 0 to 2.

Capecitabine was administered orally twice daily for 14 days followed by 7 days of rest until disease progression, death, or intolerable toxicity.

The study’s primary end point was PFS, with secondary end points that included overall survival (OS), safety, toxicity, quality of life (QoL), and tumor response.

Of the 1434 patients who registered for the trial between January 2014 and March 2020, 924 underwent successful biomarker assessment and 254 were randomly assigned evenly to either the active monitoring arm (n = 127) or the capecitabine maintenance arm (n = 127).

The OS analysis highlighted a total of 90 deaths in the active monitoring arm and 99 in the capecitabine arm. According to investigators, no survival difference between the arms was observed, with a median time to death of 15.2 months (95% CI, 12.1-18.5) in the active monitoring arm and 14.8 months (95% CI, 23.7-18.6) in the capecitabine maintenance arm. Unadjusted and adjusted HRs for these analyses were 1.00 (95% CI, 0.75-1.33; P = .98) and 0.93 (95% CI, 0.69-1.27; P = .66), respectively.

When focusing on left-sided tumors, both PFS (left-side HR, 0.38 vs right-side HR, 0.56; P = .13) and OS (left-side HR, 0.82 vs right-side HR, 1.37; P = .076) were improved with maintenance therapy.

Additionally, significantly less cumulative toxicities occurred in the active monitoring arm than in the capecitabine arm, with increased capecitabine toxicities including diarrhea, dry skin, fatigue, nausea, and palmar-plantar erythema.

Since maintenance therapy should ideally result in no toxicity, incidence of grade 0 as the worst toxicity is instructive to examine, according to the investigators. Those toxicities in both the active monitoring and capecitabine arms, respectively, included nausea (74% vs 67%), diarrhea (72% vs 46%), stomatitis (90% vs 77%), dry skin (83% vs 77%), palmar-plantar erythema (87% vs 44%), and anemia (69% vs 54%).

“Notably, these data also provide tools to best inform the dialogue between patients and clinicians on the pros and cons of the different approaches and their trade-offs,” the investigators concluded.


Adams RA, Fisher DJ, Graham J, et al. Capecitabine versus active monitoring in stable or responding metastatic colorectal cancer after 16 weeks of first-line therapy: results of the randomized FOCUS4-N Trial. J Clin Oncol. Published online September 13, 2021. doi:10.1200/JCO.21.01436

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