Secondary analyses of the randomized phase III Stop&Go study: efficacy of second-line intermittent versus continuous chemotherapy in HER2-negative advanced breast cancer.

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule.Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous).Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82-1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98-1.66) for intermittent versus continuous second-line chemotherapy. Second-line PFS was positively influenced by prior hormonal therapy for metastatic disease and longer first-line PFS duration, while triple-negative tumor status had a negative influence. Patients with a shorter time to progression (TTP) in first-line (≤10 months) had a higher probability of starting second-line treatment if they received intermittent compared to continuous chemotherapy (OR 1.97; 95% CI: 1.02-3.80).Conclusion: We recommend continuous scheduling of both the first- and second-line chemotherapy for advanced breast cancer.

The influence on quality of life of intermittent scheduling in first- and second-line chemotherapy of patients with HER2-negative advanced breast cancer.

BACKGROUND: The Stop&Go study randomized patients with advanced breast cancer to intermittent (two times four) or continuous (eight subsequent cycles) first- and second-line chemotherapy. METHODS: QoL was measured with RAND-36 questionnaires every 12 weeks. The primary objective was to estimate differences in changes from baseline between intermittent and continuous treatment. An effect size of 0.5 SD (5 points) was considered clinically meaningful. RESULTS: A total of 398 patients were included with a median follow-up of 11.4 months (IQR 5.6-22.2). Mean physical QoL baseline scores were 38.0 resp. 38.2, and mental scores 45.0 resp. 42.4 for intermittent and continuous treatment. Physical QoL declined linearly in the intermittent arm causing a clinically meaningful difference of 5.40 points at 24 months (p < 0.001), while scores in the continuous arm stabilized after a small decline of ± 3.4 points at 12 months. Conversely, mental QoL was fairly stable and even improved with 1.58 (p = 0.005) and 2.48 points (p < 0.001) at 12 months for intermittent and continuous treatment, respectively. When comparing arms for both components in changes from baseline, the maximum differences were 2.46 (p = 0.101) and 1.95 points (p = 0.182) for physical and mental scores, both measured at 30 months and in favor of continuous treatment. CONCLUSION: Intermittent first- and second-line chemotherapy in patients with HER2-negative advanced breast cancer showed a trend for worse impact on QoL compared to continuous chemotherapy, with neither significant nor meaningful differences in course. We recommend prescribing chemotherapy continuously until progressive disease or unacceptable toxicity. Trial registration EudraCT 2010-021519-18; BOOG 2010-02.

Intermittent versus continuous first-line treatment for HER2-negative metastatic breast cancer: the Stop & Go study of the Dutch Breast Cancer Research Group (BOOG).

PURPOSE: We determined if intermittent first-line treatment with paclitaxel plus bevacizumab was not inferior to continuous treatment in patients with HER2-negative, advanced breast cancer. METHODS: Patients were randomized to 2 × 4 cycles or continuous 8 cycles of paclitaxel plus bevacizumab, followed by bevacizumab maintenance treatment until disease progression or unacceptable toxicity. The primary endpoint was overall progression-free survival (PFS). A proportional-hazards regression model was used to estimate the HR. The upper limit of the two-sided 95% CI for the HR was compared with the non-inferiority margin of 1.34. RESULTS: A total of 420 patients were included with well-balanced characteristics. In the intention-to-treat analysis, median overall PFS was 7.4 months (95% CI 6.4-10.0) for intermittent and 9.7 months (95% CI 8.9-10.3) for continuous treatment, with a stratified HR of 1.17 (95% CI 0.88-1.57). Median OS was 17.5 months (95% CI 15.4-21.7) versus 20.9 months (95% CI 17.8-24.0) for intermittent versus continuous treatment, with a HR of 1.38 (95% CI 1.00-1.91). Safety results and actually delivered treatments revealed longer durations of treatment in the continuous arm, without significant unexpected findings. CONCLUSION: Intermittent first-line treatment cannot be recommended in patients with HER2-negative advanced breast cancer. CLINICAL TRIAL REGISTRATION: EudraCT 2010-021519-18; BOOG 2010-02.