ESMO Breast Cancer 2019: Does Continuous Chemotherapy Benefit Patients With Advanced Breast Cancer?


Key Points

  • Researchers noted that their analysis primarily focused on the efficacy of second-line treatment, but the updated overall survival results showed that for the whole population (those who received first-line only, or first and second lines of treatment), survival was better with continuous treatment as well.
  • Researchers saw a linear decline in physical quality-of-life scores in the intermittent-treatment arm, causing a clinically meaningful difference of 5.68 points at 24 months (P < .001), whereas scores in the continuous-treatment arm stabilized after a decline of ±3.5 points at 12 months.

Continuous chemotherapy showed greater benefit in patients with advanced breast cancer by both improving survival and maintaining quality of life compared to intermittent scheduling, according to analyses of the Stop&Go study presented by Erdkamp et al and Claessens et al at the European Society for Medical Oncology (ESMO) Breast Cancer Congress 2019 (Abstracts 158P_PR and 159P_PR).

The phase III Stop&Go trial randomly assigned 420 patients with advanced HER2-negative breast cancer to either an intermittent chemotherapy schedule (4 cycles, then a ‘treatment holiday,’ then another 4 cycles) or a continuous chemotherapy schedule comprising the same 8 cycles administered consecutively. Both first-line treatment (paclitaxel plus bevacizumab) and second-line treatment (capecitabine or nonpegylated liposomal doxorubicin) followed these schedules. The analyses presented at the ESMO Breast Cancer Congress reported on secondary endpoints from the Stop&Go study, with the main endpoint for second-line treatment being progression-free survival.


Frans Erdkamp, MD, PhD, of Zuyderland Medical Center–Sittard-Geleen, Netherlands, presented findings related to the survival benefits of continuous scheduling in both first- and second-line chemotherapy compared to intermittent therapy. “Our main focus in this analysis was on the efficacy of second-line treatment, although, interestingly, the updated overall survival results showed that for the whole population (those who received first-line only, or first and second lines of treatment), survival was better with continuous treatment as well,” said Dr. Erdkamp.

Patients who started second-line treatment (n = 270; 131 vs 139 in the intermittent vs continuous arms) demonstrated a median progression-free survival of 3.5 vs. 5.0 months, respectively (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.69–1.57). The median combined first- and second-line progression-free survival was 14.6 months in the intermittent arm vs 16.6 months in the continuous therapy arm. The median overall survival in this population was 20.3 months for the intermittent-therapy group vs 23.0 months in the continuous-therapy arm, with a hazard ratio of 1.93 (95% CI = 1.26–2.95).

Quality of Life

The study’s quality-of-life results were presented by Anouk Claessens, MD, PhD, also of Zuyderland Medical Center–Sittard-Geleen, Netherlands. “In clinical practice, we see considerable variation in treatment strategies, so we felt it would be helpful to conduct a trial investigating the effect on quality of life of scheduling with modern agents.” Dr. Claessens hypothesized that treatment holidays incorporated into scheduling would benefit quality of life.

Quality of life was measured every 12 weeks during treatment and follow-up, using RAND-36 questionnaires specifically chosen for their relevance to normal life. The course of both the physical and mental quality-of-life scores for each sequencing arm were monitored, and the difference in course was estimated between arms. The median follow-up was 11.3 months.

“With the physical quality-of-life scores, we saw a linear decline in the intermittent arm causing a clinically meaningful difference of 5.68 points at 24 months (P < .001), whereas scores in the continuous arm stabilized after a decline of ±3.5 points at 12 months,” reported Dr. Claessens.

“Comparison of the course of quality of life between the treatment arms showed the maximum differences were not statistically significant, but there was a trend for more favorable scores in the continuous arm,” she added.

“Based on our findings, you could hypothesize that the benefits of a continuous approach might be independent of the investigated treatment line and might apply to other lines of treatment as well,” said Dr. Claessens. “The challenge for clinical practice is to use agents that are well tolerated and can be continued for a prolonged period without interruptions.”

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


Commenting on the results, Nadia Harbeck, MD, PhD, of the University of Munich, said, “Both studies confirm the current national and international guidelines that chemotherapy, preferentially monotherapy (at least after first line), should be given continuously, as long as it is well tolerated and effective. 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. The new Stop&Go data confirm these older data also with more modern regimens.”

“The result that continuous chemotherapy is not at all associated with worse quality of life is clinically meaningful and further highlights the importance of preferring to administer chemotherapy continuously for benefiting the most our patients with advanced disease,” concluded Dr. Harbeck.

Disclosure: For full disclosures of the study authors, visit

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