Abstract P5-18-02: Nab-Paclitaxel-based therapy in the first line treatment of metastatic breast cancer (IBCSG 42-12/BIG 2-12 SNAP): Impact of different schedules on quality of life

Abstract

Abstract Background: The randomized phase II SNAP trial assessed three alternative reduced maintenance chemotherapy regimens using nab-Paclitaxel after a short term induction phase at conventional doses as first line treatment in patients (pts) with metastatic breast cancer (MBC). For all three regimens median progression-free survival was greater than achieved with full dose docetaxel (historical reference). Symptom palliation and quality of life (QoL) are important when deciding on therapeutic agents and schedules in MBC pts. Methods: Of the 258 pts with MBC enrolled from April 2013 to August 2015 in the SNAP trial, 255 were included in the QoL analysis. Pts were randomized to three arms, each receiving the same induction chemotherapy based on 3 cycles of nab-Paclitaxel 150 mg/m2 dd 1, 8, 15 Q28, which was reduced to 125 mg/m2 after a safety review. The schedules of nab-Paclitaxel in maintenance therapy differed in each arm: Arm A) 150 mg/m2 dd 1,15 Q28; Arm B) 100 mg/m2 dd 1,8,15 Q28; Arm C) 75 mg/m2 dd 1,8,15,22 Q28. Pts completed a QoL form to assess global and symptom-specific indicators (range 0-100) at baseline, and at day 1 of every cycle for the first 12 cycles on treatment, or until treatment discontinuation. Changes in QoL scores during induction (day 1 cycle 4 − baseline) and maintenance (day 1 cycle 12 – day 1 cycle 4) therapy were summarized descriptively per arm. Treatment effects on changes in QoL during maintenance therapy were analyzed by repeated measurement models including timepoints (from day 1 of cycle 4 to day 1 of cycle 12), induction start dose, age, and treatment arms as covariates. Results: During induction therapy, mean changes [SD] in hair loss (Arm A:−70.2 [41.9]; Arm B: −77.3 [34.5]; Arm C: −72.6 [32.8]), sensory neuropathy (Arm A: −19.0 [25.2]; Arm B: −20.6 [22.7]; Arm C: −18.8 [23.8]), and treatment burden (Arm A: −12.9 [33.4]; Arm B: −13.4 [33.5]; Arm C: −11.4 [34.8]) showed the most pronounced worsening. During maintenance therapy, scores for sensory neuropathy remained impaired without worsening. No significant differences in changes for sensory neuropathy or the other symptoms were seen between arms, except for hair loss, with pts in arm C (mean difference 10.91; 95% CI [0.35, 21.48]; p=0.04) ] and B (mean difference 18.55; 95% CI [7.52, 29.59]; p=0.001) reporting a greater improvement compared to those in arm A. Pts in arm C reported a significantly greater improvement in mood compared to arm A (mean difference 13.34; 95% CI [6.08, 20.60]; p<0.001) and arm B (mean difference 9.62; 95% CI [2.84, 16.40]; p=0.01)]. Conclusion: The effectiveness of alternative maintenance chemotherapy schedules with reduced doses after a short term induction phase at conventional doses must be weighed against a substantial worsening in sensory neuropathy during induction therapy, and scores continuing to be impaired without worsening with prolonged administration. During maintenance therapy, improvements were seen in the perception of hair loss and in mood, particularly in Arm B and C, with a similar tendency seen for some other QoL domains. A more frequent administration of reduced dose chemotherapy agents is favorable with respect to QoL in this setting. Citation Format: Ribi K, Sun Z, Jerusalem G, Hasler-Strub U, Colleoni M, von Moos R, Cortés J, Vidal M, Hennessy B, Walshe J, Amillano Parraga K, Morales Muriilo S, Pagani O, Barbeaux A, Bortsnar S, Maibach R, Regan MM, Gennari A, Bernhard J. Nab-Paclitaxel-based therapy in the first line treatment of metastatic breast cancer (IBCSG 42-12/BIG 2-12 SNAP): Impact of different schedules on quality of life [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-02.