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19 - 20 May, 2022

Low grade ovarian cancer.

Q&A

Dr.Noha Rashad.

Lecturer of medical oncology, Faculty of medicine, Suez University& AFCM.

Medical oncology consultant, Maadi Armed forces hospitals & SOH.

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Disclosures.

  • Travel grants: Roche, Bayer, Novartis and Pfizer.

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  • Honorarium: Merck, Amgen, Bayer, Novartis, Roche, Jansen, Lilly and Sanofi.

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Nomenclature of serous tumors in WHO classification:

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Low grade vs high grade serous ovarian carcinoma : clinical, prognostic and molecular features.

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LGSC

HGSC

Incidence

2% of all epithelial ovarian cancers.

4-5% of ovarian serous cancers.

~90% of serous ovarian cancer

Median age at diagnosis.

43-47 years.

median ~62 years.

Stage at diagnosis.

More advanced stage compared to HGSC.

Survival.

median OS reported 81-115 months

40.7 months.

Molecular features.

  • MAPK pathway alterations (BRAF/KRAS/NRAS/ERB2).
  • ER/PgR.
  • BRCA1/2 are rare.

P53 mutated.

BRCA1/2.

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Treatment strategies:

  • Conventional Chemotherapy: less responsive compared to high grade tumors.
  • Hormonal agents: AIs, tamoxifen, fulvestrant and leuprolide.
  • Surgery: primary treatment, secondary cytoreductive surgery.
  • Targeted therapy: bevacizumab, MAPK pathway targeting agents….etc.

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Chemotherapy for low grade ovarian serous carcinoma.

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Neoadjuvant chemotherapy:

  • Response rate 11% compared with 75% for a matched group of 36 women with high-grade serous carcinoma.

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  • Median OS for the women with low-grade serous carcinoma was only 47 months.

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  • Should be preserved for patients in whom primary resection is not feasible.

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Gynecol Oncol. 2020;158(3):653.

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Adjuvant chemotherapy:

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J.P. Grabowski et al. / Gynecologic Oncology 140 (2016) 457–462

Response rates in patients with residual disease after primary cytoreductive surgery:

OS

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Guidelines!

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ESMO guidelines 2019:

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Annals ofOncology 30: 672–705, 2019

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Chemotherapy in recurrent disease:

  • Patients should be stratified according to standard definitions for either platinum-sensitive or platinum-resistant disease.
  • the overall response rate is <4 percent.
  • Median time to progression 34.7 weeks for platinum-sensitive patients and 26.4 for platinum- resistant patients.

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Gershenson DM et al. Gynecol Oncol. 2009;114:48–52

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Hormonal therapy:

  • Maintenance hormonal therapy following platinum-based chemotherapy (letrozole vs observation):
    • Median PFS 64.9 months (95% CI: 43.5–86.3) vs. 26.4 months (95% CI: 21.8–31.0) (p < 0.001).
    • No statistically significant difference in overall survival.

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  • In relapsed disease:
    • Hormonal therapy response rate 9%.

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Gershenson DM et al. J Clin Oncol. 2017;35:1103–1111.

Gershenson DM et al. Gynecol Oncol. 2012;125:661–666.

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Bevacizumab: subgroup analysis of ICON-7 trial:

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Oza AM et al. Lancet Oncol. 2015;16:928–936.

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Surgery: a major role!

  • Primary surgery is the recommended approach for the optimal treatment of low-grade, serous carcinoma.
  • Extent of lymphadenectomy is a prognostic factor correlated with OS improvement.
  • Secondary cytoreductive surgery is considered selectively for a subset of women with relapsed, low-grade, serous carcinoma.

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B. Slomovitz, C. Gourley, M.S. Carey, et al., Low-grade serous ovarian cancer: State of the science, Gynecologic Oncology,

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Targeting MAPK pathway and other targeted agents for treatment of LGSC:

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Moujaber T et al. Endocr Relat Cancer. 2021;29(1):R1-R16.

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Thank you!

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