Outcome of Patients With Malignant Peripheral Nerve Sheath Tumors Enrolled on Sarcoma Alliance for Research Through Collaboration (SARC) Phase II Trials.

BACKGROUND: Evaluation of prior phase II trials for malignant peripheral nerve sheath tumors (MPNST) may help develop more suitable trial endpoints in future studies. METHODS: We analyzed outcomes of patients with recurrent or unresectable/metastatic MPNST enrolled on prior Sarcoma Alliance for Research through Collaboration (SARC) phase II trials and estimated the progression-free survival (PFS). PFS from SARC006 (NCT00304083), the phase II trial of upfront chemotherapy in chemotherapy naïve patients, was analyzed separately. Impact of baseline enrollment characteristics on PFS was evaluated. RESULTS: Sixty-four patients (29 male, 35 female, median age 39 years (range 15-81)) with MPNST were enrolled on 1 of 5 trials of single agent or combination therapy that were determined to be inactive. Patients had received a median of 1 (range 0-5) prior systemic therapy, and most had undergone prior surgery (77%) and radiation (61%). Seventy-three percent had metastatic disease at enrollment. Median PFS was 1.77 months (95% CI, 1.61-3.45), and the PFS rate at 4 months was 15%. Greater number of prior systemic therapies and worse performance status were associated with inferior PFS. There was no significant difference in PFS based on age at enrollment, treatment trial, response criteria, presence of metastatic disease, disease site at enrollment, and prior surgery or radiation. In comparison, on the SARC006 trial the PFS rate at 4 months was 94% in 40 patients. CONCLUSION: These data provide a historical baseline PFS that may be used as a comparator in future clinical trials for patients with MPNST.

Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension.

BACKGROUND: Bone morphogenetic protein receptor type 2 (BMPR2) mutations occur in idiopathic and familial pulmonary arterial hypertension (IPAH, FPAH); however, the impact of these mutations on clinical assessment and disease severity remains unclear. We investigated the role of BMPR2 mutations on acute vasoreactivity and disease severity in IPAH/FPAH children and adults. METHODS: BMPR2 mutation types were determined in 147 IPAH/FPAH patients. Hemodynamics were obtained at baseline and with acute vasodilator testing. RESULTS: Of 147 patients (69 adults, 78 children; 114 with IPAH, 33 with FPAH), 124 (84%) were BMPR2 mutation-negative, and 23 (16%) were mutation-positive. BMPR2 mutation-positive patients were less likely to respond to acute vasodilator testing than mutation-negative patients (4% vs 33%; p < 0.003; n = 147). BMPR2 mutation-positive children also appeared less likely to respond to acute vasodilator testing than mutation-negative children. BMPR2-positive patients had lower mixed venous saturation (57 +/- 9% vs 62 +/- 10%; p < 0.05) and cardiac index (CI; 2.0 +/- 1.1 vs 2.4 +/- 1.5 liters/min; p < 0.05) than BMPR2-negative patients. CONCLUSIONS: Patients with BMPR2 mutations are less likely to respond to acute vasodilator testing than mutation-negative patients and appear to have more severe disease at diagnosis. Determination of BMPR2 mutations appears to help identify IPAH/FPAH children and adults who are unlikely to respond to acute vasodilator testing and, thus, unlikely to benefit from calcium channel blockade (CCB) treatment.