Browsing by Author "Schuetze, Scott M."

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    A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609)
    (American Association for Cancer Research, 2022) Adams, Sylvia; Othus, Megan; Patel, Sandip Pravin; Miller, Kathy D.; Chugh, Rashmi; Schuetze, Scott M.; Chamberlin, Mary D.; Haley, Barbara J.; Storniolo, Anna Maria V.; Reddy, Mridula P.; Anderson, Scott A.; Zimmerman, Collin T.; O'Dea, Anne P.; Mirshahidi, Hamid R.; Ahnert, Jordi Rodon; Brescia, Frank J.; Hahn, Olwen; Raymond, Jane M.; Biggs, David D.; Connolly, Roisin M.; Sharon, Elad; Korde, Larissa A.; Gray, Robert J.; Mayerson, Edward; Plets, Melissa; Blanke, Charles D.; Chae, Young Kwang; Kurzrock, Razelle; Medicine, School of Medicine
    Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26-85); median number of prior therapy lines was 2 (0-5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.
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    SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors
    (Hindawi, 2017) Higham, Christine S.; Steinberg, Seth M.; Dombi, Eva; Perry, Arie; Helman, Lee J.; Schuetze, Scott M.; Ludwig, Joseph A.; Staddon, Arthur; Milhem, Mohammed M.; Rushing, Daniel; Jones, Robin L.; Livingston, Michael; Goldman, Stewart; Moertel, Christopher; Wagner, Lars; Janhofer, David; Annunziata, Christina M.; Reinke, Denise; Long, Lauren; Viskochil, David; Baker, Larry; Widemann, Brigitte C.; Department of Medicine, School of Medicine
    Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.