Breast cancer patients do better without drug holiday
Continuous chemotherapy confers better survival and quality of life than intermittent scheduling in patients with advanced breast cancer, according to the Stop&Go study presented at EBCC 2019.
“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 nature of the word, might be beneficial, but this was not the case,” said study investigator Dr Monique Bos from Erasmus University Medical Center in Rotterdam, the Netherlands.
In the phase III study, 420 patients with advanced HER2-negative breast cancer were randomized to an intermittent schedule comprising two sets of treatment cycles intermitted by a ‘treatment holiday’, or a continuous schedule of eight consecutive cycles. Both first- and second-line treatment followed these schedules, with first-line treatment consisting of paclitaxel plus bevacizumab and the second line comprising capecitabine or nonpegylated liposomal doxorubicin. [EBCC 2019, abstract 158P_PR]
The primary endpoint of progression-free survival (PFS) for the population who started second-line treatment (n=270) was 5.0 months in the continuous schedule arm compared with 3.5 months in the intermittent schedule arm (hazard ratio [HR], 1.04, 95 percent confidence interval [CI], 0.69–1.57).
When combining data for both first- and second-line treatment in this population, the PFS was also longer with continuous scheduling than with intermittent scheduling (median, 16.6 vs 14.6 months, HR, 1.59, 95 percent CI, 1.04–2.45).
Similar findings were seen for overall survival (OS) in second line (median, 12.0 vs 10.6 months, HR, 1.64, 95 percent CI, 1.08–2.48) and in combined analysis of first- and second-line treatments (median, 23.0 vs 20.3 months, HR, 1.93, 95 percent CI, 1.26–2.95).
Furthermore, both PFS (median, 13.9 vs 12.7 months, HR, 1.21, 95 percent CI, 0.9–1.63) and OS (median, 20.9 vs 17.1 months, HR, 1.37, 95 percent CI, 1.03–1.54) for the entire randomized population (n=420, inclusive of those who receive first-line treatment only, or both first- and second-line treatments) were also longer with continuous vs intermittent scheduling.
“In clinical practice, we see considerable variation in treatment strategies, so felt it would be helpful to conduct a trial investigating the effect on quality of life (QoL) of scheduling with modern agents,” said lead author of another subanalysis of the Stop&Go study, Dr Anouk Claessens from Zuyderland Medical Center–Sittard-Geleen, Geleen, the Netherlands.
Among the 398 patients analysed on QoL every 12 weeks over a median follow-up of 11.3 months, physical QoL was stable after a ±3.5-point decline at 1 year in the continuous schedule arm, while there was a linear decline to a point whereby the difference was clinically meaningful (5.68 points; p<0.001) from baseline at 2 years in the intermittent arm. [EBCC 2019, abstract 159P_PR]
Mental QoL improved in both arms at 12 months, by 1.86 points (p=0.012) in the intermittent arm and by 2.53 points (p=0.001) in the continuous arm.
“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,” said Professor Nadia Harbeck from the Ludwig Maximilian University of Munich (LMU), Munich, Germany.
“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,” he added.