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Introduction: Nirogacestat is a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors. In the phase 3 DeFi study (NCT03785964) of nirogacestat, ovarian toxicity (OT) was identified as a safety signal among females of reproductive potential (FORP). This analysis further describes the incidence, presentation, and resolution of OT. Methods: Patients were randomized to twice‐daily oral nirogacestat (150 mg) or placebo, taken in continuous 28‐day cycles. Investigator‐identified OT in FORP was based on abnormal reproductive hormone values or perimenopausal symptoms (or both). Adverse event follow‐up was conducted to assess OT resolution. Post hoc analyses included return of menstruation and return of follicle‐stimulating hormone (FSH) to within normal limits (WNL) (≤20.4 mIU/mL). Results: Of 92 randomized females, 73 in the safety population were FORP (n = 36 nirogacestat, n = 37 placebo). OT was identified in 75% (27 of 36) receiving nirogacestat and 0% (0 of 37) receiving placebo. As of October 24, 2022, investigators reported OT resolution in 78% (21 of 27) of patients, with median OT duration of 19.1 weeks. Off‐treatment resolution was reported in all 11 patients (100%) who stopped nirogacestat treatment; of these, all nine with available menstruation information experienced return of menstruation and eight had FSH WNL at last reported assessment. Resolution was reported in 10 of 14 (71%) while on nirogacestat; of these, all 10 experienced return of menstruation and seven had FSH WNL. Two patients were lost to follow‐up. Conclusion: Most FORP treated with nirogacestat experienced OT, with the majority resolving, including all who stopped treatment, suggesting that OT is transient. In the phase 3 DeFi study of nirogacestat, a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors, ovarian toxicity was identified as a safety signal in most females of reproductive potential. The majority (78%) of ovarian toxicity events resolved, including in 100% of patients who stopped nirogacestat for any reason, suggesting that ovarian toxicity with nirogacestat is transient. [ABSTRACT FROM AUTHOR]

Background: Due to inherent impact on quality of life, metastatic head and neck cancer patients are well‐suited to benefit from palliative care (PC). Our objective was to examine factors that shape PC utilization and implications for overall survival in stage IVc head and neck cancer patients. Methods: A retrospective study of patients with stage IVc head and neck cancer in the National Cancer Database from 2004 and 2015 was conducted. Results: 7794 cases met inclusion criteria, of which 19.3% received PC. PC use was associated with more recent years of diagnosis, Northeast facility geography, and non‐private insurances (p < 0.05). Compared to no PC, "interventional" PC, defined as palliative surgery, radiation, and/or chemotherapy, and "pain management only" PC were associated with lower overall survival (p < 0.05). Conclusions: PC use increased over time and was associated with demographic and clinical factors. There remains opportunity for improvement in optimal implementation of palliative care. [ABSTRACT FROM AUTHOR]

Background: This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable or metastatic conventional chondrosarcoma.Methods: Eligible patients had conventional chondrosarcoma of any grade with measurable tumors that were unresectable or metastatic. Patients with mesenchymal, dedifferentiated, and extraskeletal myxoid chondrosarcoma subtypes and patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28-day cycles. Tumor responses were evaluated by local radiology assessments every 2 cycles. The primary endpoint was the disease control rate (DCR) at week 16 (4 cycles).Results: Forty-seven patients were enrolled. The DCR at 16 weeks was 43% (95% confidence interval [CI], 28%-58%), which was superior to the null hypothesis rate of 30%, but the 2-sided P value (exact test) was .09 (1-sided P = .045). One patient had a partial response. The median overall survival was 17.6 months (95% CI, 11.3-35.0 months), and the median progression-free survival was 7.9 months (95% CI, 3.7-12.6 months). Grade 3 or higher adverse events were infrequent; hypertension (26%) and elevated alanine aminotransferase (9%) were most common.Conclusions: This study provides evidence of positive drug activity for pazopanib in conventional chondrosarcoma. [ABSTRACT FROM AUTHOR]

Abstract: Background: Leiomyosarcoma is a rare neoplasm of the head and neck. The purpose of this study was to present our single‐institution case series of head and neck leiomyosarcoma and a review of cases in the National Cancer Data Base (NCDB). Methods: Patients with head and neck leiomyosarcoma at the University of Pennsylvania and in the NCDB were identified. Demographic characteristics, tumor factors, treatment paradigms, and outcomes were evaluated for prognostic significance. Results: Nine patients with head and neck leiomyosarcoma from the institution were identified; a majority had high‐grade disease and cutaneous leiomyosarcoma, with a 5‐year survival rate of 50%. Two hundred fifty‐nine patients with leiomyosarcoma were found in the NCDB; macroscopic positive margins and high‐grade disease were associated with poor prognosis (P < .01), and positive surgical margins were related to adjuvant radiation (P < .001). Conclusion: Head and neck leiomyosarcoma presents at a high grade and is preferentially treated with surgery. Several demographic and tumor‐specific factors are associated with outcomes and prognosis. [ABSTRACT FROM AUTHOR]

Background Granulocytic sarcoma is an extramedullary tumor of myeloblasts. The purpose of this report was to present a case of a primary laryngeal granulocytic sarcoma and review of the literature. Methods A literature review was performed using Medline and PubMed databases to search for cases of all primary and secondary myelogenous tumors of the larynx. Results A 36-year-old man presented with a mass involving the preepiglottic space that was histologically confirmed as an extramedullary acute myeloid leukemia, or granulocytic sarcoma. Our review found 18 cases of secondary involvement of the larynx by myelogenous tumors, and only 1 previously reported case of primary laryngeal granulocytic sarcoma. Conclusion The detection of granulocytic sarcoma is difficult given its rarity and nonspecific presentation. To our knowledge, this is the second reported case of primary granulocytic sarcoma of the larynx reported in the literature. © 2014 Wiley Periodicals, Inc. Head Neck 37: E38-E44, 2015 [ABSTRACT FROM AUTHOR]

Preventing chemotherapy-induced thrombocytopenia could avoid chemotherapy dose reductions and delays. The safety and maximum tolerated dose of eltrombopag, an oral thrombopoietin receptor agonist, with gemcitabine-based therapy was evaluated. Patients with advanced solid tumors and platelets ≤300 × 109/L receiving gemcitabine plus cisplatin or carboplatin (Group A) or gemcitabine monotherapy (Group B) were randomized 3:1 to receive eltrombopag or placebo at a starting dose of 100 mg daily administered on days −5 to −1 and days 2-6 starting from cycle 2 of treatment. Nineteen patients (Group A, n = 9; Group B, n = 10) received eltrombopag 100 mg and seven (Group A, n = 3; Group B, n = 4) received matching placebo. Nine eltrombopag patients in Group A and eight in Group B had 38 and 54 occurrences of platelet counts ≥400 × 109/L, respectively. Mean platelet nadirs across cycles 2-6 were 115 × 109/L and 143 × 109/L for eltrombopag-treated patients versus 53 × 109/L and 103 × 109/L for placebo-treated patients in Groups A and B, respectively. No dose-limiting toxicities were reported for eltrombopag; however, due to several occurrences of thrombocytosis, a decision was made not to dose-escalate eltrombopag to >100 mg daily. In Groups A and B, 14% of eltrombopag versus 50% of placebo patients required chemotherapy dose reductions and/or delays for any reason across cycles 3-6. Eltrombopag 100 mg once daily administered 5 days before and after day 1 of chemotherapy was well tolerated with an acceptable safety profile, and will be further tested in a phase II trial. Fewer patients receiving eltrombopag required chemotherapy dose delays and/or reductions compared with those receiving placebo. [ABSTRACT FROM AUTHOR]