Abstract P5-16-03: Peripheral sensory neuropathy occurrence and resolution: Results from the neoadjuvant randomized GeparSepto study (GBG 69)
Authors: Furlanetto J , von Minckwitz G , Jackisch C , Schneeweiss A , Aktas B , Denkert C , Wiebringhaus H , Kuemmel S , Warm M , Paepke S , Just M , Hanusch C , Hackmann J , Blohmer J-U , Clemens M , Costa SD , Gerber B , Nekljudova V , Untch M , Loibl S 
Published: March 2017

Abstract
Background: The GeparSepto (NCT01583426) study showed that nab-paclitaxel (nP) increases the pathological complete response (ypT0 ypN0) rate when it replaces paclitaxel (P) as part of a sequential taxane followed by epirubicin/cyclophosphamide (EC) neoadjuvant chemotherapy for pts with early breast cancer (BC) (Untch Lancet Oncol 2016). After a safety analysis showed a higher rate of dose reductions, treatment discontinuations as well as peripheral sensory neuropathy (PSN) with nP 150 mg/m2 w (nP150) compared to P 80mg/m2 w, dose of nP was reduced to 125 mg/m2 w (nP125). The risk-benefit ratio of nP125 was improved over nP150 (von Minckwitz SABCS 2015). We reported follow-up (FU) data on PSN occurrence and resolution.
Methods: Pts with untreated BC received P 80mg/m2 w or nP 150/125mg/m2 w followed by four cycles of E 90 mg/m2 plus C 600 mg/m2 q3w, with trastuzumab 6 mg/kg (loading (LD) dose 8 mg/kg) and pertuzumab 420 mg (LD 840 mg) q3w if HER2+. After the end of the study the protocol was amended in order to collect long-term data on PSN outcome as well as on treatment modalities. PSN will be reported according treatment and dose received on day 1.
Results: Overall 601 pts received P80; 220 pts nP150 and 385 pts nP125 on day 1. PSN grade 2-4 was observed in 18.8% (n=113/601) of pts treated with P80 and in 41.8% (n=92/220) vs 39.2% (n=151/385) with nP150 and nP125 respectively (p=0.547). Grade 3-4 PSN was reported for 2.7% (n=16/601) of pts in the P80 group and 14.5% (n=32/220) vs 8.1% (n=31/385) in the nP150 vs nP125 group respectively (p=0.018). In 31.8% (36/113), 35.9% (33/92) and 27.2% (41/151), PSN was not resolved at the end of the treatment (EOT); PSN grade 3-4 was not resolved in 37.5% (6/16), 56.3% (18/32) and 58.1% (18/31). After a median FU of 110 weeks after EOT, data on PSN status for pts with unresolved PSN grade 2-4 were available from 30, 22 and 32 pts; 26 pts did not provide update information (n=7 died, n=5 data not yet available, n=14 status unknown). For 63.3% (n=19), 40.9% (n=9) and 56.2% (n=18) of pts, PSN grade 2-4 was resolved to grade 1. Time to resolve (TTR) of PSN grade 2-4 was significantly different between nP150 and nP125 (p&lt;0.001); no significant difference was seen between P and nP (p=0.405) [Tab.1]. After a median FU of 103 weeks after EOT, data on PSN status of pts with unresolved PSN grade 3-4 were available for 6, 14 and 14 pts. For 66.6% (n=4), 42.8% (n=6) and 50.0% (n=7) of pts PSN grade 3-4 was resolved to grade 1. TTR of PSN grade 3-4 was not significantly different neither for nP150 vs nP125 (p=0.103) nor for P vs nP (p=0.120) ) [Tab.1].
Conclusions: nP125 is associated with a lower occurrence of PSN compared to nP150 but higher PSN than P80. If PSN occurred nP125 is associated with a more rapid resolution compared to nP150. Nearly 10.7% had no resolution of PSN so far. Further FU and markers for selecting pts at risk are needed.
The trial is supported by Celgene.
Table 1. Median time to resolution (mTTR) of PSN to grade 1comparison groupsmTTR n (weeks); [95% CI]P vs nPPnP150nP125grade 2-47 [6-9]8 [6-10]grade 3-49 [4-15]17 [5-123]nP150 vs nP125 grade 2-4 13 [9-15]6 [4-9]grade 3-4 56 [11-170]17 [10-nr]abbreviations: nP, nab-paclitaxel; P, paclitaxel; nr, not reached
Citation Format: Furlanetto J, von Minckwitz G, Jackisch C, Schneeweiss A, Aktas B, Denkert C, Wiebringhaus H, Kuemmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer J-U, Clemens M, Costa SD, Gerber B, Nekljudova V, Untch M, Loibl S. Peripheral sensory neuropathy occurrence and resolution: Results from the neoadjuvant randomized GeparSepto study (GBG 69) [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 P5-16-03.