(P 460) OUTCOMES OF LATER-LINES SYSTEMIC THERAPIES IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (MPNST)

Objective: MPNSTs are rare sarcomas known for high rates of recurrence and metastasis with limited systemic treatment (ST) options. While doxorubicin/ifosfamide (AI) is the most efficacious 1st line ST, there is little data about subsequent regimens. We sought to establish outcomes of ST in later line settings as a baseline for future studies.

Methods: Baseline characteristics, treatment data and outcomes were collected from locally advanced/metastatic neurofibromatosis type 1 (NF1)-related and sporadic (non-NF1) MPNST patients (pts) treated with ST at MD Anderson Cancer Center (n=154). Chi squared and Fisher’s exact tests were used for comparisons between groups. Survival outcomes were estimated by Kaplan-Meier method and compared with log-rank test.

Results: Out of 112 NF1 and 42 non-NF1 MPNST pts, the median age at diagnosis was 30 and 52 years, respectively. Trunk was the most common location for both NF1 and non-NF1 (50% and 57.1%), followed by extremities (25% and 31%). Of the 130 pts with follow-up scans, the response rate (RR) and median PFS for 1st line treatment was 20% (19/93) and 3.1 mo (95%CI 2.5-5.8) in NF1 and 37.8% (14/37) and 5.9 (2.8-10) mo in non-NF1. Of these pts, 69, 26, 9, and 1 received 2nd, 3rd, 4th, and 5th line therapy, respectively. AI was the most common in the 1st line setting (46.2%) while gemcitabine/docetaxel (GT) was commonly used in ≥2nd line (22.8%). The RR of any ST in ≥ 2nd lines was lower (11.5%, 12/105); 5.6% (4/71) in NF1 and 23.5% (8/34) in non-NF1. The mPFS of ≥ 2nd line regimens was 1.9 mo (95%CI 1.6-2.4) in NF1 and 3.8 mo (2-6.5) in non-NF1 (p 0.0045). Median OS was 23.2 mo. (19.6-28.5) and 47.5 mo. (28.3-NR) in NF1 and non-NF1 (p 0.0017). The table lists the outcomes for regimens used in ≥ 5 pts in any line.

Conclusion: Significant attrition of pts occurs after 1st line therapy in this cohort, likely attributable to aggressive disease biology and lack of effective 2nd line therapy options. Non-NF1 showed better RR and PFS compared to NF-1 MPNST for each of the regimens.