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Treatment Holiday Flops in Advanced Breast Cancer

Advanced breast cancer patients given a treatment break fared worse than those who received continuous therapy, the randomized Stop&Go trial found.

Combined median overall survival (OS) was 20.3 months for HER2-negative patients on an intermittent schedule during first- and second-line therapy compared with 23.0 months for those on continuous treatment (HR 1.93, 95% CI 1.26-2.95), according to Frans Erdkamp, MD, PhD, of Zuyderland Medical Center in Sittard-Geleen, the Netherlands.

The combined progression-free survival (PFS) was significantly shorter as well, at 14.6 months for the intermittent group and 16.6 months for the continuous group (HR 1.59, 95% CI 1.04-2.45).

In a separate analysis of the trial, Anouk Claessens, MD, PhD, also of Zuyderland Medical Center, reported that quality of life (QOL) outcomes were no better in the group on the intermittent treatment schedule, who had a mean 5.68-point decline at 2 years in physical QOL scores (P<0.001). In the continuous arm, QOL scores stabilized at 1 year following a smaller decline.

Findings from Stop&Go will be presented this week at the European Society for Medical Oncology Breast Cancer Congress in Berlin.

“We were a little surprised at the findings running contrary to our hypothesis,” co-author Monique Bos, MD, PhD, of Erasmus University Medical Center in Rotterdam, said in a statement. “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.”

The phase III study included 420 advanced HER2-negative breast cancer patients who were given first-line treatment of paclitaxel plus bevacizumab (Avastin) and randomized to continuous chemotherapy (8 cycles) or an intermittent schedule (4 cycles, a break, then 4 more cycles). The same schedule was used in second-line, where patients received either capecitabine (Xeloda) or non-pegylated liposomal doxorubicin (Myocet).

“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 Nadia Harbeck, MD, PhD, of the University of Munich.

“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 Harbeck, who was not involved in the research. “The new Stop&Go data confirm these older data also with more modern regimens.”

She noted that the findings on QOL further highlight the importance of administering chemotherapy continuously for patients with advanced breast cancer.

For the full cohort, median combined first- and second-line PFS was 12.7 months with the intermittent schedule and 13.9 months with continuous treatment, a non-significant difference, while overall survival was 17.1 and 20.9 months, respectively (HR 1.37, 95% CI 1.03-1.54). Patients with HR-positive disease, longer disease-free interval following first-line therapy, good baseline performance status, and no visceral metastases predicted second-line treatment.

Examining PFS from the time of second-line treatment, there was no significant difference between the two groups, at 3.5 months with intermittent treatment and 5.0 months with continuous treatment, but OS was worse with the intermittent schedule (10.6 vs 12.0 months, HR 1.64, 95% CI 1.08-2.48).

The QOL analysis included 398 patients and used RAND-36 questionnaires to measure mental and physical QOL scores every 12 weeks during the treatment portion of the trial and then throughout follow-up. For physical QOL, average baseline scores were 37.9 for the intermittent group and 38.3 for the continuous group. For mental QOL, mean scores were 44.7 and 42.5, respectively. At 1 year, mental QOL improved by 1.86 points in the intermittent arm (P=0.012) and 2.53 points in the continuous arm (P=0.001).

The study was funded by Roche and Teva Pharmaceutical Industries in the Netherlands.

Erdkamp disclosed relevant relationships with Roche and Novartis. Claessens disclosed no relevant relationships. One co-author of the two studies disclosed relevant relationships with Roche, Novartis, Lilly, and Pfizer.