Citations

AbstractBackgroundA bridging nerve autograft is the gold standard for the repair of segmental nerve injury that cannot be repaired directly. However, limited availability and donor site morbidity remain major disadvantages of autografts. Here, a nerve allograft decellularized with elastase was compared with an autograft regarding functional motor outcome in a rat sciatic segmental nerve defect model. Furthermore, the effect of storage on this allograft was studied.MethodsSixty‐six Lewis rats (250–300 g) underwent a 10‐mm sciatic nerve reconstruction using either a cold‐ (n = 22) or frozen‐stored (n = 22) decellularized nerve allograft or an autograft (n = 22). Sprague–Dawley rats (300–350 g) served as full major histocompatibility complex‐mismatched donors. Functional motor outcome was evaluated after 12 and 16 weeks. Ankle angle, compound muscle action potential (CMAP), isometric tetanic force, wet muscle weight, and histomorphometry were tested bilaterally.ResultsFor CMAP and isometric tetanic force, no significant differences were observed between groups. In contrast, for ankle angle, histomorphometry and muscle weight, the cold‐stored allograft performed comparable to the autograft, while the frozen‐stored allograft performed significantly inferior to the autograft. At week 16, ankle angle was 88.0 ± 3.1% in the cold‐stored group, 77.4 ± 3.6% in the frozen‐stored group, and 74.1 ± 3.1% in the autograft group (P < .001); At week 16, the muscle weight showed a recovery up to 71.1 ± 4.8% in the autograft group, 67.0 ± 6.6% in the cold‐stored group, and 64.7 ± 3.7% in the frozen‐stored group (P < .05).ConclusionsA nerve allograft decellularized with elastase, if stored under the right conditions, results in comparable functional motor outcomes as the gold standard, the autograft.

1088 Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003.