Abstract P5-15-05: Randomized phase II study evaluating different schedules of nab-paclitaxel in metastatic breast cancer (MBC): Results of the SNAP study
Authors: Gennari A , Sun Z , Hasler-Strub U , Colleoni M , Kennedy J , von Moos R , Cortes J , Vidal M , Hennessy B , Walshe J , Amillano Parraga K , Morales Murrillo S , Pagani O , Barbeaux A , Borstnar S , Rabaglio M , Maibach R , Regan MM , Jerusalem G 
Published: March 2017

Background

Longer chemotherapy (CT) duration is associated with a significant improvement in progression-free survival (PFS) and a moderate, but significant improvement in overall survival (OS) in MBC patients (pts). Prolonged CT administration, however, must be weighed against the side effects of continuous CT delivery. The SNAP trial was designed to improve the tolerability of prolonged CT by studying alternative treatment schedules.

Methods

The SNAP trial enrolled 258 women from April 2013 to Aug 2015. Eligibility criteria included HER2- MBC, no prior CT for advanced disease, measurable and/or non-measurable disease.

All eligible pts were randomized to one of three arms. Pts received the same induction chemotherapy consisting of 3 cycles of nab-Paclitaxel given days 1,8,15 Q28, followed by one of the three maintenance therapy schedules. Originally, the dose of the induction chemotherapy was 150 mg/m2, but this was reduced to 125 mg/m2 following the first safety review of 48 treated pts. The three schedules of nab-Paclitaxel used as maintenance therapy were (Arm A) nab-Paclitaxel 150 mg/m2 d 1,15 Q28; (Arm B) nab-Paclitaxel 100 mg/m2 d 1,8,15 Q28; (Arm C) nab-Paclitaxel 75 mg/m2 d 1,8,15,22 Q28.

The primary objective is to evaluate the efficacy of three nab-Paclitaxel regimens as measured by progression-free survival (PFS), using the historical reference of PFS (based on AVADO study) of docetaxel for first-line treatment of metastatic breast cancer. Each of the three regimens is compared to the historic 7-month median PFS to determine whether any of the three regimens are worthy of further investigation. Secondary endpoints include tolerability, feasibility, response rate, OS and QoL.

Results

Two-hundred-fifty-eight pts have been randomised and 255 are available for primary endpoint evaluation. At 18.2 months' median follow-up, 182 PFS events and 85 deaths have been observed. Median PFS was 7.9 months (90%CI 6.8-8.4) in Arm A, 9.0 months (90%CI 8.1-10.9) in Arm B and 8.5 (90%CI 6.7-9.5) in Arm C. PFS in Arm B was significantly longer than the historic PFS of first-line docetaxel (one-sided log-rank p=0.03).

As expected, neurotoxicity was the most frequent adverse event. In the induction phase, grade≥2 sensory neuropathy was reported in 14.8% of pts at the starting dose of 150 mg/m2 and 7.5% at the starting dose of 125 mg/m2; grade≥3 sensory neuropathy occurred in 2.5% and 0% of the pts, respectively. In the maintenance phase, grade≥2 sensory neuropathy was reported in 37.9% of pts in Arm A, 36.1% in Arm B and 31.2% in Arm C; grade≥3 sensory neuropathy occurred in 9.1%, 5.6% and 6.6% of the pts, respectively.

199 pts started the maintenance phase. The median number of maintenance cycles was 3, 4, and 5, respectively. Stopping maintenance for reasons other than objective progression occurred in 41%, 58%, and 53%, respectively.

Conclusion

The SNAP trial indicates that alternative maintenance chemotherapy schedules with reduced doses after a short term induction phase at conventional doses are feasible and significantly more active than the historical PFS of docetaxel in the first line treatment of advanced breast cancer.

Citation Format: Gennari A, Sun Z, Hasler-Strub U, Colleoni M, Kennedy J, von Moos R, Cortes J, Vidal M, Hennessy B, Walshe J, Amillano Parraga K, Morales Murrillo S, Pagani O, Barbeaux A, Borstnar S, Rabaglio M, Maibach R, Regan MM, Jerusalem G. Randomized phase II study evaluating different schedules of nab-paclitaxel in metastatic breast cancer (MBC): Results of the SNAP study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-05.