New Findings on Continuous vs Intermittent Chemotherapy in Advanced Breast Cancer

A continuous schedule of chemotherapy administration resulted in improved overall survival compared with an intermittent schedule in a study of patients with advanced breast cancer. A second analysis showed that the intermittent schedule also results in worse quality of life than a continuous schedule.

Guidelines do recommend that chemotherapy, in particular after the first line of therapy, should be given continuously, but some clinicians recommend a treatment “holiday” for some patients with advanced breast cancer. The phase III Stop&Go trial randomized 420 patients with advanced HER2-negative breast cancer to either an intermittent schedule (4 cycles followed by a treatment holiday followed by 4 more cycles) or a continuous schedule comprised of the 8 cycles given continuously. The results will be presented by Frans Erdkamp, MD, PhD, of the Zuyderland Medical Center in the Netherlands, at the European Society for Medical Oncology (ESMO) Breast Cancer Congress, held May 2–4 in Berlin.

The study included patients who received only first-line chemotherapy (paclitaxel plus bevacizumab) and those who went on to receive second-line therapy as well (capecitabine or non-pegylated liposomal doxorubicin). Among the 270 patients who began second-line therapy, the median progression-free survival was 3.5 months with intermittent chemotherapy and 5.0 months with continuous treatment, for a hazard ratio (HR) of 1.04 (95% CI, 0.69–1.57). Overall survival was improved with continuous therapy, at a median of 10.6 months with intermittent treatment and 12.0 months with continuous therapy, for an HR of 1.64 (95% CI, 1.08–2.48).

In that same group, when their first- and second-line outcomes were combined, the median progression-free survival was 14.6 months with intermittent therapy and 16.6 months with continuous therapy, for an HR of 1.59 (95% CI, 1.04–2.45). The median overall survival in this analysis was 20.3 months and 23.0 months, respectively, for an HR of 1.93 (95% CI, 1.26–2.95).

When the full 420-patient cohort was considered, the median first- and second-line progression-free survival was 12.7 months with intermittent scheduling and 13.9 months with continuous treatment, for an HR of 1.21 (95% CI, 0.9–1.63). The median overall survival was 17.1 months and 20.9 months, respectively, for an HR of 1.37 (95% CI, 1.03–1.54).

“We were a little surprised at the findings running contrary to our hypothesis,” said one of the co-investigators, Monique Bos, MD, PhD, of Erasmus University Medical Center in Rotterdam, in a press release. “In explaining therapy schedules to patients we tend to suggest that a ‘holiday,’ by nature of the word, might be beneficial, but this was not the case.”

This was confirmed in a secondary analysis of quality of life in the trial, results of which were presented at the ESMO conference by Anouk Claessens, also of the Zuyderland Medical Center. A total of 398 patients in the trial were assessed using RAND-36 questionnaires. The physical quality-of-life scores declined linearly in patients treated intermittently, with a clinically meaningful drop of 5.68 points at 24 months (P < .001). In the continuous group, those scores stabilized after a decline at 12 months.

With regard to mental quality-of-life scores, those in the intermittent group had an increase of 1.86 points at 12 months (P = .012), though this was larger in the continuous group at 2.53 points (P = .001).

“Until now, we’ve only had evidence from older studies, with regimens no longer used, indicating that continuous chemotherapy in metastatic disease is better than shorter,” said Nadia Harbeck, MD, PhD, of the University of Munich, who commented on the study for ESMO. “The new Stop&Go data confirm these older data also with more modern regimens.” She also stressed that the finding that continuous treatment does not result in worsened quality of life is “clinically meaningful.”