Fibroid Management: What’s new?

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10/14/20211

Fibroid Management: What’s new?

Alison F. Jacoby, MD

Department of Obstetrics, Gynecology andReproductive Sciences

Disclosures�None

Fibroid Management: What's new?


10/14/20212

Learning Objectives�Provide clinically relevant information to inform your treatment

decision making and advice to your patients


Learning ObjectivesWhat’s new in fibroid basic science?

• What can our patients do to prevent fibroid development and growth?

• What is the evidence for vitamins?



10/14/20213

Learning ObjectivesWhat’s new in fibroid medical therapy?

• Moving beyond progestins and birth control pills

• New FDA-approved medications


Learning ObjectivesWhat’s new in fibroid surgical treatment?

• New studies comparing Myomectomy vs Hysterectomy

• New(ish) procedures:

• Laparoscopic radiofrequency ablation (Acessa™)

• Transcervical fibroid ablation (Sonata™)



10/14/20214

The #1 Question I’m asked…


What causes fibroids?

And the corollary question…

How can I prevent new fibroids from developing?



10/14/20215

Complementary Treatments

Epigallocatechin (EGCG)

• Anti-proliferative• Anti-inflammatory• Antioxidant• Animal and in vitro

– Inhibit proliferation and induce apoptosis in fibroid cells

Zhang et al, Fertil Steril 2010 and AJOG 2010

Green Tea Randomized TrialPlacebo-controlled trialN=39EGCG 800mg vs. PlaceboFibroid symptomsHgb (11.7 to 12.4 (g/dL)

Fibroid volume 33%

-No information on baseline fibroid volume-No U.S. data

Roshdy et al, J Women’s Health, 2013


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Complementary Treatments


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Vitamin DAND….• Reduces cell proliferation• Increases apoptosis• Regulates extracellular matrix

(ECM)• Regulates gene transcription

of ER/PR

May protect against:• Cardiovascular disease• Cancer (breast, colorectal)• Autoimmune disease• Uterine fibroids

• Bone health• Calcium hemostasis

Vitamin D: Epidemiologic Evidence• Women with sufficient levels of vitamin D (>20ng/mL) less likely to have uterine fibroids

(OR 0.68, CI 0.48-0.96), N=1,036

Baird et al. Epidemiology 2013;24:447-53

• Women with vitamin D deficiency more likely to have fibroids ( OR 2.5, CI 1.2-4.9), N=384

Paffoni et al. J Clin Endocrinol Metab 2013;98:E1374-8

• Inverse relationship between vitamin D and fibroid size

Sabry et al. Int J Womens Health 2013;5:93-100


10/14/20218

Practical advice�Evidence for green tea extract is limited but supported by an RCT

�Vitamin D has the most evidence for playing a central role in fibroid pathogenesis

�Consider checking Vit D levels + recommending supplementation

�Safe and effective dose has not been determined


New medical therapies for fibroidsGnRH antagonist, estradiol and norethindrone


Obstet Gynecol 2018; 132(5): 1252-1264


10/14/20219

New medical therapies for fibroidsOral GnRH antagonist, estradiol and norethindrone


N Engl J Med 2021; 384: 630-42

Elagolix combination therapy�First oral medication approved to treat heavy menstrual bleeding from

uterine fibroids: May 2020

�Twice daily dosing

AM: Elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg

PM: Elagolix 300 mg

Primary Endpoint:

• % who achieve menstrual blood loss (MBL) < 80 mL and at least 50% less MBL from start of study



10/14/202110

Relugolix combination therapy�Relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg QD

�FDA approved in 2021 for controlling excess menstrual bleeding caused by uterine fibroids in premenopausal women

�Duration of use: 2 yrs


N Engl J Med 2021; 384: 630-42

Relugolix combination therapyLiberty study� 770 women randomized to placebo, relugolix alone or relugolix

combo therapy

�Treatment x 24 wks

�Mean age 42 yrs

�Baseline menstrual blood loss: 230 mL

�Baseline uterine volume: 400 cm3



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Relugolix combination therapyLiberty study24 wk Outcomes:

�< 80mL menstrual blood loss: 72% in relugolix gps vs 17% of controls

�Amenorrhea: 51% vs 4.5%

�Reduction in uterine volume: -13% vs +2.2%


Relugolix combination therapyLiberty study�Contraindications: pregnancy, undiagnosed AUB, current or hx of

breast ca or other hormone sensitive malignancies, known osteoporosis, liver disease, high risk for thrombosis

�Adverse reactions:

Hot flashes- 10.6% relugolix combo vs 6.6% placebo

AUB- 6.3% vs 1.2%

Bone loss- minimal difference



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New medical therapies for fibroids� UPA = oral selective progesterone receptor modulator

� European trials showed that UPA is > placebo and non-inferior to leuprolide in ↓ bleeding and fibroid volume AND has fewer hypoestrogenic symptoms and effects on bone turnover

Obstetrics & Gynecology: November 2018 - Volume 132 -Issue 5 - p 1241-1251

RESULTS• 432 were randomized to one of the 6 treatment arms• 274 (63%) completed study

• Primary Outcome: Rate of and time to amenorrhea in course 1.

• Rates of amenorrhea were 42.0% (97.5% CI 33.3–51.1) and 54.8% (97.5% CI 45.5–63.8) for 5 mg and 10 mg ulipristal, respectively, compared with 0% (97.5% CI 0.0–3.8) for placebo.

• AE: only hot flushes occurred more commonly in UPA groups than placebo groups; no SAEs considered treatment related

•


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Discussion- Ulipristal

� Intermittent treatment with daily doses of 5mg or 10mg ulipristal was > placebo in management of abnormal bleeding in women with symptomatic uterine leiomyomas

� The efficacy of both doses was maintained during the second course of treatment after an off-treatment interval of two menses.

� Reduced leiomyoma volume when data were log- transformed to control for clinical variability

� No evidence for ulipristal-induced liver injury in EU studies, during 6 years of post-marketing experience, rare cases of serious liver injury were reported in patients treated with ulipristal

� Conclusion: “intermittent 12-week courses of treat ment with ulipristal, followed by off-treatment intervals, may be conside red a preferred option for the medical management of symptomatic uterine l eiomyomas, particularly for women desiring uterine-sparing the rapy”

New Surgical Studies


Fertil Steril 2020; 113: 618-26


10/14/202114

�Objective: To compare long-term health-related quality of life (HRQOL) 1 year after hysterectomy or myomectomy for treatment of uterine fibroids (UFs) and to determine whether route of procedure, race, or age affected improvements in HRQOL

�Design: Prospective cohort study

�Setting: Eight clinical sites throughout the United States

�Patients: A total of 1,113 premenopausal women with UFs who underwent hysterectomy or myomectomy

�Main Outcome Measures: Self-reported HRQOL and Uterine Fibroid Symptom Quality of Life (UF-QOL)


Results:

�Hysterectomy patients were older with a longer history of symptomatic UF compared with myomectomy patients

�HRQOL improved after both surgeries

�When stratified across race/ethnicity and age, hysterectomy had higher HRQOL scores compared with myomectomy

�There was little difference in HRQOL or symptom severity between abdominal hysterectomy and abdominal myomectomy.



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Conclusions:

�HRQOL improved in all women 1 year after hysterectomy or myomectomy

�Hysterectomy patients reported higher HRQOL summary scores compared with myomectomy patients however the absence of bleeding after hysterectomy favors the symptom severity score

� When stratified by route, minimally invasive hysterectomy had better HRQOL scores than minimally invasive myomectomy. There was little difference in scores with abdominal approaches.


Radiofrequency Ablation of Fibroids

Generator with Foot Pedal

3mm RF Handpiece

Laparoscopic Ultrasound

• FDA approved for fibroids November 2012(Acessa™)



10/14/202116

Radiofrequency Fibroid Ablation


Radiofrequency Ablation of Fibroids• Fibroids identified with

ultrasound (1cm incision)

• Radiofrequency (RF) probe placed under ultrasound guidance (3mm incision)

• Monopolar RF energy delivered to fibroids

• Tissue heats to 1000 C to cause coagulative necrosis

• Fibroid cells reabsorbed



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RF Ablation: Current Evidence• Largest study, n=135

• Industry funded, FDA pivotal trial

• Uncontrolled, all women treated with RF ablation

Chudnoff et al, Obstet Gynecol, May 2013

Fibroid criteria•<14 week uterus•<6 fibroids•<7cm fibroid•<300cm3 volume


RF Ablation: Current Evidence

Chudnoff et al, Obstet Gynecol May 201352% decrease in symptom score



10/14/202118

RF Ablation: Current Evidence

Uterine Volume Fibroid Volume

3 months -15% (CI 11-20)* -40% (CI 36-44)*

12 months -24% (CI 19-30)* -45% (CI 39-52)*

*P<.001Chudnoff et al, Obstet Gynecol, May 2013

Change in Fibroid and Uterine Volume from Baseline


RF Ablation: Current Evidence• Adverse events: 4%

• Pregnancy (“not recommended” per FDA)

• Not studied in women who desire future fertility

• Insufficient data on pregnancy outcomes

• Treatment Failure

• <1% at 1 year (1/135)

• 4.4% at 2 years (6/129)

• 4.5% at 3 years (4/88)

• TOTAL 11/135=8%Chudnoff et al, Obstet Gynecol May 2013Guido et all, Health and Quality of Life Outcomes 2013, 11;139



10/14/202119

RF Ablation: Ongoing StudiesULTRA: Uterine Leiomyoma Treatment with Radiofrequency Ablation)

• Nationwide post-market study of Acessa

• 3 years of follow-up to assess change in symptoms, treatment failure, pregnancy outcomes (NCT02100904)


Transcervical Fibroid Ablation�Targeted RF ablation with intrauterine ultrasound guidance

�Sonata® System

� Ideal for type II & III submucosal fibroids



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Transcervical Fibroid Ablation�Pivotal trial completed, FDA approved 5/2020

�FAST-EU study: N=50

3 months 12 monthsFibroid volume -54.7±37.4% -66.6±32.1%

Symptom score -46.7 + 32.8% -55.1±41.0 %

Reoperation 8%

Brolmann et al, Gynecol Surg, 2016



10/14/202121

In Conclusion:�Possible role for Vitamin D, especially in Vit D deficient patients

�Promising results for oral GnRH antagonists with add back

�Ulipristal effective but risk of liver injury blocked FDA approval

�Myomectomy outcomes comparable to hysterectomy

�Fibroid ablative procedures show promising results


THANK YOU


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Fibroid Management: What’s new?