Glenn J Hanna1, Anne ONeill2, Jennifer M Cutler3, Michelle Flynn3, Tushara Vijaykumar4, John R Clark5, Lori J Wirth5, Jochen H Lorch3, Jong C Park5, Jeffrey K Mito6, Jens G Lohr4, Jeffrey Kaufman7, Nicole Spardy Burr7, Leonard I Zon8, Robert I Haddad3. 1. Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA. Electronic address: glenn_hanna@dfci.harvard.edu. 2. Department of Data Science, Dana-Farber Cancer Institute, Boston, USA. 3. Department of Medical Oncology, Center for Head & Neck Oncology, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston, USA. 4. Center for Hematologic Oncology, Dana-Farber Cancer Institute, Boston, USA. 5. Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, USA. 6. Department of Pathology, Brigham & Women's Hospital, Boston, USA. 7. Adenoid Cystic Carcinoma Research Foundation, USA. 8. Department of Stem Cell and Regenerative Biology, Boston Children's Hospital and Harvard Medical School, Boston, USA.
Abstract
BACKGROUND: Effective therapies are lacking for recurrent, metastatic adenoid cystic carcinoma (R/M ACC) and preclinical models suggest retinoic acid agonists inhibit ACC growth. This phase II trial evaluated all-trans retinoic acid (ATRA) as a novel therapy for ACC. METHODS: Patients with R/M ACC (any site) with clinical and/or radiographic progression ≤12 months prior to study entry were eligible. Cohort 1 (CH1) received ATRA 45 mg/m2 split oral daily dosing on days 1-14 of a 28-day cycle; Cohort 2 (CH2) received the same dosing continuously. Primary endpoint was best overall response rate (CR + PR) (RECIST v1.1). Secondary endpoints: safety and progression-free survival (PFS). Exploratory analyses: ATRA impact on MYB expression and genomic predictors of response. RESULTS: Eighteen patients enrolled. There were no responses, but 61% (11/18) had stable disease (SD) and 28% (5/18) progression as best response; 11% (2/18) unevaluable. Median duration of stability: 3.7 months (95%CI, 1.9-3.9). One patient (CH1) remains on drug with SD approaching 1 year. Half of those who received prior VEGFR therapy achieved SD (4/8). At median follow up of 7.9 months, median PFS was 3.2 months (95%CI, 1.8-3.9). N = 1 required dose adjustment; N = 1 came off drug for toxicity. There were no grade 3-4 adverse events. NOTCH1 and PI3K pathway alterations were most frequent. Low MYB protein expression was associated with longer duration of stability on ATRA (P < 0.01). CONCLUSION(S): While the trial did not meet its prespecified response endpoint, ATRA alone or in combination may be a low toxicity treatment for disease growth stabilization in R/M ACC.
BACKGROUND: Effective therapies are lacking for recurrent, metastatic adenoid cystic carcinoma (R/M ACC) and preclinical models suggest retinoic acid agonists inhibit ACC growth. This phase II trial evaluated all-trans retinoic acid (ATRA) as a novel therapy for ACC. METHODS: Patients with R/M ACC (any site) with clinical and/or radiographic progression ≤12 months prior to study entry were eligible. Cohort 1 (CH1) received ATRA 45 mg/m2 split oral daily dosing on days 1-14 of a 28-day cycle; Cohort 2 (CH2) received the same dosing continuously. Primary endpoint was best overall response rate (CR + PR) (RECIST v1.1). Secondary endpoints: safety and progression-free survival (PFS). Exploratory analyses: ATRA impact on MYB expression and genomic predictors of response. RESULTS: Eighteen patients enrolled. There were no responses, but 61% (11/18) had stable disease (SD) and 28% (5/18) progression as best response; 11% (2/18) unevaluable. Median duration of stability: 3.7 months (95%CI, 1.9-3.9). One patient (CH1) remains on drug with SD approaching 1 year. Half of those who received prior VEGFR therapy achieved SD (4/8). At median follow up of 7.9 months, median PFS was 3.2 months (95%CI, 1.8-3.9). N = 1 required dose adjustment; N = 1 came off drug for toxicity. There were no grade 3-4 adverse events. NOTCH1 and PI3K pathway alterations were most frequent. Low MYB protein expression was associated with longer duration of stability on ATRA (P < 0.01). CONCLUSION(S): While the trial did not meet its prespecified response endpoint, ATRA alone or in combination may be a low toxicity treatment for disease growth stabilization in R/M ACC.
Authors: María Cascallar; Sandra Alijas; Alba Pensado-López; Abi Judit Vázquez-Ríos; Laura Sánchez; Roberto Piñeiro; María de la Fuente Journal: Cancers (Basel) Date: 2022-04-30 Impact factor: 6.575
Authors: Lauren E Miller; Vivienne Au; Tara E Mokhtari; Deborah Goss; Daniel L Faden; Mark A Varvares Journal: Cancers (Basel) Date: 2022-02-16 Impact factor: 6.639