(P 187) BRIDGING THE GAP: UNDERSTANDING THE CURRENT TREATMENT RESPONSES TO ENHANCE THE STANDARD OF CARE AND OUTCOMES FOR MALIGNANT PERIPHERAL NERVE SHEATH TUMORS

Objective: Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue sarcoma that makes up 5-10% of all sarcoma cases with a prevalence of one in 100,000 in the general population. There is currently no effective targeted therapy to treat MPNST and surgical resection remains the mainstay of treatment, though often not feasible due to location or size of the tumor, or presence of metastases. Evaluation of MPNST treatment response to palliative chemotherapy regimens could serve as a reference point for target response rates in clinical trials going forward.

Methods: We performed a retrospective electronic health record analysis of patients with biopsy-proven diagnoses of MPNST at Washington University and Johns Hopkins Hospital. We evaluated tumor characteristics along with treatment response, overall survival (OS), and progression free survival (PFS) rates for different chemotherapeutic regimens.

Results: The cohort comprised 140 patients, with ages at diagnosis ranging from 21 to 40 years. Most patients had tumors located in the extremities, with sizes ranging from 5-15 cm at the time of diagnosis. We identified 66 patients who received adjuvant chemotherapy, 44 received neoadjuvant chemotherapy and 28 did not receive any chemotherapy. Neoadjuvant chemotherapy demonstrated an objective response rate (ORR) of 13.89% (5 out of 36 patients) and a clinical benefit rate of 69.45% (25 out of 36 patients) which included patients with stable disease (SD) or partial response (PR) to treatment. Among patients with metastatic disease (n=57), 9 chemotherapy regimens were assessed with a median PFS ranging from 1.84 months (0.98-12.62) to 10.38 months (3.28-22.26). First line chemotherapy regimens that were associated with a median PFS of four months or more included doxorubicin-based regimens and vincristine-irinotecan-temozolomide. Among second line and subsequent therapies regimens, ifosfamide-etoposide, ipilimumab-nivolumab, irinotecan-temozolomide and trabectidin achieved a PFS of four months or more.

Conclusion: Despite advancements in therapy, MPNST carries a poor prognosis and is a leading cause of mortality in patients with neurofibromatosis type 1. Our study has identified several systemic therapies which should be further evaluated prospectively to improve treatment options and outcomes for patients with this aggressive sarcoma. These results can also serve as a benchmark for future clinical trials.