Oral Bexarotene Research Articles

A case of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T‐cell lymphoma

AbstractA 65‐year‐old Japanese woman with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T‐cell lymphoma, a rare type with a poor prognosis, is presented. Oral bexarotene and vorinostat were ineffective, and hematopoietic stem cell transplantation was scheduled. We stress that primary cutaneous CD8+ aggressive epidermotropic cytotoxic T‐cell lymphoma should be treated with bone marrow transplantation when available.

Effects of Body Mass Index on Hypertriglyceridemia Associated with Oral Bexarotene Therapy: A Post Hoc Analysis of an Open-Label Comparative Clinical Study of Combined Bexarotene and Phototherapy Versus Bexarotene Monotherapy for Japanese Patients with Cutaneous T-Cell Lymphoma.

Bexarotene, which has been approved for use in Japan since 2016, is an effective drug for cutaneous T-cell lymphoma; however, careful management is imperative because of its adverse events. We previously demonstrated the severity of bexarotene-associated hypertriglyceridemia and the need for bexarotene dose reduction for patients with cutaneous T-cell lymphoma and high body mass index (BMI); however, high BMI does not affect the efficacy of combined bexarotene and phototherapy treatment. This study aimed to verify the effects of BMI on hypertriglyceridemia associated with oral bexarotene therapy. We conducted a post hoc analysis of data from a previous randomized, open-label clinical study that compared combined bexarotene-phototherapy treatment with bexarotene monotherapy for cutaneous T-cell lymphoma by dividing patients into two groups based on BMI (<23 kg/m2 and ≥23 kg/m2). No statistically significant association was observed between patients with BMI ≥23 kg/m2 and severe hypertriglyceridemia; however, there was a significant association between BMI ≥23 kg/m2 and severe hypertriglyceridemia for patients who received bexarotene monotherapy, but not for those who received combined bexarotene-phototherapy treatment. The exact reasons for the discrepancies between the results of this thorough analysis and those of our past research are unclear. However, high BMI may be a risk factor for hypertriglyceridemia. Additional unidentified risk factors could also affect treatment outcomes. High BMI is the primary reason for hypertriglyceridemia-associated bexarotene dose reduction; however, unexplored risk factors other than high BMI could exist.

FRI511 Bexarotene: A Deceptive Cause Of Iatrogenic Hypothyroidism

Abstract Disclosure: S. Ghaith: None. A. Ramachandran: None. C. Alcorn: None. F. Amer: None. A. Thompson: None. A. Ramachandran: None. Background: Bexarotene, an antineoplastic agent used for the treatment of cutaneous T cell lymphoma, is associated with a rapid and profound suppression of thyrotropin, which may lead to central hypothyroidism. Case: A Seventy-four-year-old female with a recent diagnosis of Cutaneous T cell lymphoma presented with a 1-week history of progressive fatigue, lightheadedness, and night sweats. She was found to have hypotension and hypothermia. She was started on oral Bexarotene chemotherapy 225 mg daily five days prior to admission. The physical exam was unremarkable except for sinus bradycardia and hypothermia. Labs were significant for TSH 0.48 [0.4-4.2 uIU/mL] dropped from 3.3 uIU/mL one week prior, FT4 0.5 [0.8-1.7 ng/dL] and Total T3 111 ng/dL [87- 187 ng/dL] consistent with central hypothyroidism. Bexarotene was held during her hospitalization per hematology recommendations. The patient was started on Levothyroxine 50 mcg, which was later advanced to 75 mcg daily based on free T4 levels. At one month follow up, free T4 level normalized while on Levothyroxine and Bexarotene was restarted again by her hematologist. Discussion: Bexarotene, an antineoplastic agent approved for treating cutaneous T cell lymphoma, can rapidly suppress TSH levels by directly inhibiting its secretion and affect thyroid hormone metabolism, leading to central hypothyroidism. The degree of suppression of TSH increases with higher doses of Bexarotene while reduction in free T4 and TSH are reversible. Patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels. If bexarotene is permanently discontinued, levothyroxine can either be stopped or can be resumed to doses used prior to bexarotene therapy. Recovery of thyroid function usually occurs within weeks of Bexarotene discontinuation. Conclusion: Oral Bexarotene can cause central hypothyroidism therefore, thyroid function tests should be measured at baseline and treatment. Thyroid hormone replacement should be considered if central hypothyroidism is suspected. Presentation: Friday, June 16, 2023

Indolent adult T‐cell leukaemia‐lymphoma successfully treated with bexarotene in an eldery patient

AbstractAdult T‐cell leukaemia‐lymphoma (ATL) is a mature T‐cell malignancy, with more than 50% of cases showing cutaneous involvement. Patients with cutaneous‐type ATL (cATL) in the indolent type (i.e., favourable chronic or smouldering type) can usually be managed by watchful waiting and they are primarily treated with skin‐directed therapies until the disease progresses to acute crisis, with multiple tumours usually considered intractable. ATL tends to present in older patients, and those with multiple cATL tumours face difficulties in obtaining multiagent chemotherapy used for aggressive types. Although bexarotene is a third‐generation novel retinoid X receptor‐selective retinoid treatment that is effective for cutaneous T‐cell lymphoma, few reports have demonstrated its effectiveness for cATL. We describe an 86‐year‐old woman with cATL treated safely and successfully with a combination of oral bexarotene and skin‐directed therapies, despite renal dysfunction and previous hypothyroidism. After 10 months of treatment, we observed neither new tumours nor disease recurrence, with complete response maintained at 24 months until now while continuing bexarotene. Our experience suggests that oral bexarotene is an effective treatment option, even for elderly patients with cATL.

ATOPIC DERMATITIS IN 86-YEAR-OLD MAN? BETTER THINK TWICE…

<h3>Introduction</h3> Erythematous, pruritic rashes are commonly encountered by the Allergist. Clinicians should have awareness of the presentation and diagnostic challenge of cutaneous T-cell lymphomas to diagnose this disease instead of one of its more benign impersonators. <h3>Case Description</h3> An 86 yo man presented with six months of a pruritic rash involving his arms, back, abdomen, thighs, and buttocks. The rash was composed of dry and erythematous patches with excoriations. Serum IgE had increased from 267 IU/mL to 18,800 IU/mL during this period. Four skin biopsies demonstrated lichenoid and perivascular lymphocytic infiltrate with eosinophils, concerning for drug eruption, however, no culprit medication could be identified. Due to the clinical presentation, there was suspicion for cutaneous T-cell lymphoma, specifically early mycosis fungoides (MF). Although perivascular lymphocytic infiltrate can be found in early MF, it is non-specific, and did not confirm a diagnosis based on the criteria set forth by the ISCL. Ultimately, Clonal TRG V1-8,9 + J1/2 rearrangement was detected in peripheral blood, and the patient started oral bexarotene, a retinoic acid derivative, as treatment for MF. He underwent PET-CT and bone marrow biopsy, which were negative for peripheral T-cell lymphoma. At his most recent follow-up with Allergy, the patient had only intermittent pruritus, with no rash noted on examination. <h3>Discussion</h3> The diagnosis of early MF is challenging as the clinical and histopathological findings in the initial stages mimic a variety of inflammatory skin conditions. In this case, when biopsy results were non-specific, gene rearrangement studies were critical in leading to the correct diagnosis and treatment.

Treatment of early-stage mycosis fungoides with oral bexarotene and phototherapy: A systematic review and meta-analysis.

Mycosis fungoides (MF) is a rare subtype of non-Hodgkin lymphoma, for which no standard treatment exists. The objective of this study is to provide evidence-based recommendations for adult patients with early-stage MF treated with oral bexarotene and phototherapy. A systematic review and meta-analysis was conducted utilizing studies identified via Embase, Pubmed, Web of Science, and the Cochrane Library from inception to April 2020 to evaluate the clinical efficacy and adverse events of oral bexarotene and phototherapy. Of 645 abstracts retrieved, 17 full-text articles with 143 subjects were included for analysis. There were nine case reports, five retrospective cohort studies, two prospective cohort studies, and one randomized controlled trial. Most subjects were men (24.48%) with stage IB disease (54.4%), and the mean age at presentation was 63. One patient had folliculotropic disease. The retrospective studies' analysis included 67 subjects and indicated that the partial response was 40.36% (95% CI 18.24-64.92), complete response was 34.06% (95% CI 10.73-62.56), and overall response was 64.48% (95% CI 48.56-78.89). Side effects from bexarotene were hypertriglyceridemia (54%), hypothyroidism (50%), and hypercholesterolemia (46%). Similar results were noted in the prospective studies. The literature consists mostly of uncontrolled studies, which suggest that combination therapy with oral bexarotene and phototherapy is a therapeutic option. Future randomized control studies with longer follow-up and standardized definitions of treatment responses and dosages are needed to support the development of evidence-based approaches for the treatment of early-stage MF.

Comparison of the Efficacy and Safety of Bexarotene and Photo(Chemo)Therapy Combination Therapy and Bexarotene Monotherapy for Cutaneous T-Cell Lymphoma.

IntroductionCutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. The combined use of therapeutic agents and photo(chemo)therapy is widely applied for the treatment of CTCL. The efficacy and safety of bexarotene and photo(chemo)therapy combination therapy were previously confirmed in Japanese patients with CTCL. The efficacy and safety of the bexarotene and photo(chemo)therapy combination therapy was compared with bexarotene monotherapy in Japanese patients with CTCL.MethodsThis was a randomized, open-label, two-parallel-group, active-control specified clinical study in Japanese patients diagnosed with CTCL carried out over 8 weeks with a study extension conducted at two institutions. This study was registered in Japan Registry of Clinical Trials (jRCTs041180094).ResultsIn the combination therapy group, 22 subjects received oral bexarotene (300 mg/m2 body surface area) once daily, followed by bath-psoralen and ultraviolet (UV) A or narrowband UVB. In the monotherapy group, 24 subjects received oral bexarotene (300 mg/m2) once daily. The efficacy analysis using the modified Severity-Weighted Assessment Tool, which included 39 patients, showed a response rate of 81.0% (17/21) in the combination therapy group and 83.3% (15/18) in the monotherapy group. No statistically significant difference was detected between groups. In the combination therapy group, four subjects showed a complete clinical response or complete response, and subjects with a partial response exhibited a high rate of skin lesion resolution, significantly better than in the monotherapy group. In the safety analysis, which included 46 treated subjects (22 in the combination therapy group and 24 in the monotherapy group), no adverse events or adverse drug reactions were reported in either group.ConclusionBoth bexarotene and photo(chemo)therapy combination therapy and bexarotene monotherapy were therapeutically effective in Japanese patients with CTCL and well tolerated. Combination therapy led to a higher skin lesion resolution rate and greater therapeutic effects compared with monotherapy.Trial RegistrationjRCTs041180094.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00655-0.

Low-dose total skin electron beam therapy plus oral bexarotene maintenance therapy for cutaneous T-cell lymphoma.

Total skin electron beam therapy (TSEBT) combined with systemic therapy or maintenance treatment is a reasonable approach to enhance the remission rate and duration in mycosis fungoides (MF) and Sézary syndrome (SS). This study assesses the efficacy of oral bexarotene therapy after low-dose TSEBT for patients with MF and SS. In this prospective observational study, we recruited MF/SS patients for treatment with low-dose total skin electron beam therapy (TSEBT) with or without bexarotene therapy to describe outcomes and toxicities. Forty-six subjects with MF or SS underwent TSEBT between 2016 and 2021 at our institute. Following TSEBT, 27 patients (59%) received oral bexarotene treatment. The median follow-up was 13 months. The overall response rate (ORR) for the cohort was 85%. The response rate was significantly higher with combined modality (CM) than TSEBT alone (96% vs. 68%, p = 0.03). Median progression-free survival (PFS) for the CM was 17 months versus five months following TSEBT alone (p = 0.001). One patient (4%) in the retinoid group discontinued the bexarotene therapy because of adverse events. The administration of bexarotene therapy did not increase radiation-related toxicities. Response rate and progression-free survival might be improved with TSEBT in combination with oral bexarotene compared to TSEBT alone.

Efficacy and Safety of Oral Bexarotene for Japanese Patients with Mycosis Fungoides : A Retrospective Case-Series Study of a Single Medical Center in Japan

Efficacy and Safety of Oral Bexarotene for Japanese Patients with Mycosis Fungoides : A Retrospective Case-Series Study of a Single Medical Center in Japan

Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study

Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18-50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene-placebo difference 0·16 pu, 95% CI -0·39 to 0·71; p=0·55). We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Multiple Sclerosis Society of the United Kingdom.

Disease characteristics, prognosis, and response to therapy in patients with large-cell transformed mycosis fungoides: A single-center retrospective study

Mycosis fungoides with large-cell transformation (MF-LCT) is associated with an aggressive clinical course, yet data comparing treatment outcomes in MF-LCT are sparse. To compare treatment outcomes and to determine disease prevalence and characteristics associated with survival in MF-LCT. A retrospective review was conducted of mycosis fungoides patients from 2012 to 2020 treated at Thomas Jefferson University. Patients with histopathologic diagnosis of MF-LCT were included. Treatment outcomes were assessed by mean changes in the modified Severity Weighted Assessment Tool (mSWAT) and stage. Of 171 patients with mycosis fungoides, 23 (13.4%) had histologic diagnosis of MF-LCT. The overall 5-year survival rate for MF-LCT was 74% and was not significantly associated with sex, age, or initial stage at the time of MF-LCT diagnosis. Brentuximab vedotin showed the greatest mean decrease in mSWAT (-20.53) and stage progression (change in Δ stage: -0.4) in MF-LCT compared to oral bexarotene (ΔmSWAT: +4.51; Δstage: +0.27), skin-directed therapy (ΔmSWAT: -5.93; Δstage: -0.08), and chemotherapy (ΔmSWAT: +4.97; Δstage: +0.85). Single-center retrospective design, and patients often on multiple treatment modalities. We report superior treatment outcomes for brentuximab vedotin compared to oral bexarotene, skin-directed therapy, and chemotherapy in MF-LCT in both early and advanced disease.

Abstract PS8-12: Interim analysis of a phase I dose escalation study of topical bexarotene in women at high risk for breast cancer

Abstract Background: Breast cancer prevention with anti-estrogens, including tamoxifen, raloxifene, and exemestane, has been shown to reduce the incidence of hormone receptor-positive breast cancer. However, agents that can reduce the incidence of hormone receptor negative breast cancer are currently lacking. Rexinoids such as bexarotene are vitamin A analogues that have been shown to be involved in cell differentiation, growth, and apoptosis. In preclinical mouse models that develop ER-negative breast cancers, bexarotene showed a significant reduction in mammary tumor development. Oral bexarotene has been evaluated in BRCA mutation carriers and significant decreases in cyclin D1 were noted in breast cells suggesting biological activity of bexarotene on breast tissue. Systemic side effects of hyperlipidemia and hypothyroidism were also found. Data from chemoprevention studies with topical 4-hydroxytamoxifen support the concept of topical agents penetrating into the breast tissue and exhibiting biological activity. We hypothesize that topical bexarotene can be applied to the breast as a prevention agent with penetration into the breast tissue and without subsequent systemic side effects as seen with oral bexarotene. Methods: Women at high risk for breast cancer were recruited and assigned to escalating doses of 1% topical bexarotene: 10mg (1ml) every other day, 10mg (1ml) daily and 20mg (2ml) daily for 4 weeks. Cohorts of 3-4 participants were enrolled and fully evaluated through 4 weeks prior to enrolling the next cohort. Each dose level enrolled a maximum of 10 participants. The primary endpoint of the study was to determine the recommended phase II dose of topical bexarotene 1% gel for evaluation in healthy at-risk women. Dose Limiting Toxicity (DLT) was defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event related to the study drug. A grade 2 skin adverse event that recurs and persists for at least 3 days is also a DLT. The Maximum Tolerated Dose (MTD) was defined as the highest dose level at which no more than 2 participants experience a DLT among 10 participants treated. Once the MTD was determined, interim biomarker analysis will be completed to assess bexarotene levels in serum and tissue samples. An expansion cohort of an additional 10 patients will be recruited at the MTD to further evaluate safety and toxicity. Secondary endpoints include serum bexarotene level, tissue bexarotene levels, and changes in thyroid function tests, lipid profile, and calcium. Results: Ten women were enrolled at the dose level of 10mg every other day and 9/10 participants experienced Grade 1 skin related events at the application site. Two participants reported Grade 2 skin related events at the application site but did not last long enough to be considered DLTs. Four women were enrolled at the second dose level of 10mg daily and 3/4 experience Grade 2 skin related events including 2 DLTs which stopped accrual to the study. Therefore, the MTD was determined to be 10mg every other day. No laboratory abnormalities were noted across either dose level and no grade 3 or 4 adverse events were reported. Conclusion: Maculopapular rash at treatment site was the most common adverse event related to study drug and resolved with discontinuation. Analysis is ongoing to assess bexarotene drug levels in serum and breast tissue samples. Citation Format: Parijatham S Thomas, Anisha B Patel, Diane Liu, J. Jack Lee, Seema Khan, Miguel Muzzio, Alejandro Contreras, Lana Vornik, Eileen P Dimond, Marjorie Perloff, Brandy Heckman-Stoddard, Powel H Brown. Interim analysis of a phase I dose escalation study of topical bexarotene in women at high risk for breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-12.

Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Drug options for the life‐threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4‐LBD) and induces a conformational change in the secondary structure of TR4‐LBD. Bexarotene suppressed AtT‐20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4‐increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5’ promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH‐secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.

503 Outcomes of patients with cutaneous T-cell lymphoma (CTCL) treated with extracorporeal photopheresis (ECP): A single institution experience

ECP is an established therapy for CTCL yet patterns of utilization, complication rates, and outcomes vary widely among treatment centers. We hereby report our experience with 13 patients (pts) treated with ECP from 2013-2019; median age was 65 (range 47-87) years. All pts had advanced stage CTCL; 8 (61.5%) with mycosis fungoides (MF) and 5 (38.5%) with Sezary syndrome (SS). Median time from diagnosis to pheresis start was 2.8 months with a median of 2 lines of prior therapy. All pts initially started on a ECP regimen of 2 consecutive days per week with 8 (61.5%) pts concurrently using oral bexarotene (Bex) and subcutaneous interferon alpha (IFN), 2 pts on ECP alone (15.4%), 2 (15.4%) with Bex only, and 1 (7.7%) with IFN only.

Abstract OT2-09-02: A phase I dose escalation study of topical bexarotene in women at high risk for breast cancer

Abstract Background: Breast cancer prevention with anti-estrogens, including tamoxifen, raloxifene, and exemestane, has been shown to reduce the incidence of hormone receptor-positive breast cancer. However, agents that can reduce the incidence of hormone receptor negative breast cancer are currently lacking. Rexinoids such as bexarotene are vitamin A analogues that have been shown to be involved in cell differentiation, growth, and apoptosis. In preclinical mouse models that develop ER-negative breast cancers, bexarotene showed a significant reduction in mammary tumor development. Oral bexarotene has been evaluated in BRCA mutation carriers and significant decreases in cyclin D1 were noted in breast cells suggesting biological activity of bexarotene on breast tissue. Systemic side effects of hyperlipidemia and hypothyroidism were also found. Data from chemoprevention studies with topical 4-hydroxytamoxifen support the concept of topical agents penetrating into the breast tissue and exhibiting biological activity in the tissue. We hypothesize that topical bexarotene can be applied to the breast as a chemoprevention agent with penetration to the breast tissue without subsequent systemic side effects and toxicity as seen with oral bexarotene. Trial Design: Women at high risk for breast cancer will be recruited and assigned to one of three different dose levels: 10mg (1ml) every other day, 10mg (1ml) daily, 20mg (2ml) daily to one unaffected breast for 4 weeks. The primary endpoint of the study is to determine the recommended phase II dose of topical bexarotene 1% gel for evaluation in healthy at-risk women. Dose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event related to the study drug. A grade 2 skin adverse event that recurs and persists for at least 3 days is also a DLT. The Maximum Tolerated Dose (MTD) will be defined as the highest dose level at which no more than 2 participants experience a DLT among 10 participants treated. A conservative modification of the standard “3+3” design will be applied. The first three participants will be assigned to the lowest dose level. New cohorts of 3-4 participants will not be treated until toxicity has been fully evaluated for all current participants through 4 weeks. Once the MTD has been determined, an expansion cohort of an additional 10 patients will be recruited at the MTD to further evaluate safety and toxicity at this dose level as well bexarotene concentration in the breast tissue. Secondary endpoints include serum bexarotene level, tissue bexarotene levels, and changes in thyroid function tests, lipid profile, and calcium. The planned accrual for this study if maximally accrued to all dose levels and the dose expansion cohort will be 40 participants. Citation Format: Thomas PS, Patel AB, Contreras A, Liu DD, Lee JJ, Khan S, Vornik LA, Dimond EP, Perloff M, Heckman-Stoddard BM, Brown PH. A phase I dose escalation study of topical bexarotene in women at high risk for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-09-02.

Efficacy of Mogamulizumab By Prior Systemic Therapy in Patients with Previously Treated Cutaneous T-Cell Lymphoma: Post Hoc Analysis from the Phase 3 Mavoric Study

Efficacy of Mogamulizumab By Prior Systemic Therapy in Patients with Previously Treated Cutaneous T-Cell Lymphoma: Post Hoc Analysis from the Phase 3 Mavoric Study

Treatment of Rosai–Dorfman disease with oral bexarotene: a case series

Background: Rosai–Dorfman disease (RDD) is a rare histiocytic proliferative disorder of unknown etiology. The skin is the most frequent extranodal site of RDD involvement and may be the only organ involved. While RDD is an indolent self-limited disease, treatment is needed in patients with extensive, persistent or progressive disease, or if cosmetic disfigurement or physical impairment significantly affects the patient. There is no specific treatment for RDD, and multiple therapeutic approaches have been described with variable success rates.Ojective: To demonstrate the clinical efficacy of oral bexarotene for RDD.Materials and methods: Descriptive retrospective case series of three patients with RDD receiving oral bexarotene.Results: Two patients had excellent response and regression of their skin lesions was achieved with long-term therapy. In the other patient, pruritus was promptly controlled while the lesions did not seem to regress and treatment was discontinued after five months.Conclusions: Our case series is the first report in the literature of the use of oral bexarotene as an effective and safe treatment for RDD.

A phase I/II study of bexarotene with carboplatin and weekly paclitaxel for the treatment of patients with advanced non-small cell lung cancer.

Rexinoids demonstrate anti-proliferative differentiation-inducing activity in multiple cancer types, including NSCLC. Prior studies have shown promising results when combining rexinoids with chemotherapy. This phase I/II study evaluates the tolerability and activity of a rexinoid, bexarotene, combined with weekly paclitaxel and monthly carboplatin. Patients with confirmed advanced stage IIIB or IV NSCLC and adequate organ function were enrolled. They were scheduled to receive carboplatin (AUC =6) and 3 doses of weekly paclitaxel (100 mg/m2) every 4 weeks. Oral bexarotene was administered daily at two doses: 300 and 400 mg/m2/day. Thirty-three patients were enrolled. Fourteen received 300 mg/m2/day and 19 received 400 mg/m2/day of bexarotene. Hematologic toxicity included grade 3 neutropenia in 7 patients. Hyperlipidemia was a major non-hematologic toxicity which was medically managed. The recommended phase II dose of bexarotene was 400 mg/m2/day. Response rate was 35%. Median overall survival (OS) for all patients was 8.3 months with 1-year survival of 43%. Median OS for the 300 mg/m2 dose of bexarotene was 6.6 versus 9.8 months for the 400 mg/m2 dose (HR, 0.73; Log rank P=0.37). Patients who experienced hypertriglyceridemia had a median OS of 9.8 months compared to 4.9 months for those who did not (HR, 0.69; Log rank P=0.33). The 43% 1-year survival for patients receiving bexarotene with weekly paclitaxel and monthly carboplatin is encouraging. With the availability of new classes of agents for lung cancer, further evaluation of this regimen in unselected patients is not warranted. Our study confirms prior subgroup analyses showing a significant correlation between bexarotene-induced hypertriglyceridemia and survival. Further research is needed to identify molecular biomarkers to identify this subset of patients and to explore rexinoids in other combinations, especially with immunotherapy.

PO-0735: Low dose Total Skin Irradiation followed by maintenance with oral Bexarotene in Mycosis Fungoides

PO-0735: Low dose Total Skin Irradiation followed by maintenance with oral Bexarotene in Mycosis Fungoides

Abstract 188: Preventive effect of aerosolized bexarotene in three major subtypes of lung cancer: adenocarcinoma, squamous cell carcinoma and small cell lung cancer in mice

Abstract Lung cancer is the leading cause of cancer-related deaths in the United States. The 5 year survival rate for lung cancer patients has remained a dismal 15% for 3 decades. Thus, the development of chemopreventive agents that could prevent lung cancer could potentially reduce the incidence and mortality of pulmonary neoplasms. Bexarotene has exhibited inhibitory effects in preclinical in vivo models of mammary and lung tumorigenesis, has been approved for clinical use in the treatment of cutaneous T-cell lymphoma, and has shown efficacy in phase I/II trials of non-small cell lung cancer (NSCLC). Preclinical studies have demonstrated that it is highly effective in the prevention of all three major subtypes of lung cancer in mouse models: adenocarcinoma (AD), squamous cell carcinoma (SCC), and small cell lung cancer (SCLC). The major side effects of bexarotene when administered orally to rodents or human patients have been hypertriglyceridemia and hypercholesterolemia. Previous studies in a mouse model of lung AD have demonstrated that aerosol delivery of bexarotene through nasal inhalation exhibited potent chemopreventive activity similar to that observed following oral administration (59 to74% reductions in lung tumor multiplicity). The significant decreases in tumor multiplicity and tumor load were achieved without hypertriglycerides that accompany oral bexarotene administration. In this study, aerosolized delivery of 10-30 mg/ml bexarotene showed a significant chemopreventive effect in all three major subtypes. In the N-nitroso-tris-chloroethylurea (NTCU) induced mouse SCC model, 1 week after the first dose of NTCU a dose dependent decrease in tumor formation was observed, with the highest dose causing 75% (p&amp;lt;0.001) and 42% (p&amp;lt;0.01) decreases in SCC tumor burden and the percentage of SCC tumors, respectively. Tumor load was decreased by 73% in A/Jp53 mouse AD model and by 41% in A/Jp53Rb mouse SCLC model. Aerosol delivery of bexarotene had no effect on animal body weight and other signs of toxicity, and no effect on triglyceride and cholesterol level. Aerosolized bexarotene formulation was effective against all 3 major lung cancer cell types and would be a major advance achieving significant reductions in preventing lung cancer incidence in persons at high risk of lung cancer e.g. former or present smokers. Citation Format: Qi Zhang, Jing Pan, Marker S. Miller, Ronald A. Lubet, Yian Wang, Ming You. Preventive effect of aerosolized bexarotene in three major subtypes of lung cancer: adenocarcinoma, squamous cell carcinoma and small cell lung cancer in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 188. doi:10.1158/1538-7445.AM2017-188