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EP991 Exceptional response with combined anti-hormone and MEK inhibitor therapy in a patient with hormone receptor-positive ovarian cancer and isolated KRAS alteration. Implications for a precision medicine strategy
  1. K Takahashi1,2,
  2. S Kato3,
  3. K Bamel3,
  4. S Ikeda1,
  5. S Plaxe3,
  6. B Parker3 and
  7. R Kurzrock3
  1. 1Cancer Center
  2. 2Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Medical Hospital, Tokyo, Japan
  3. 3Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA


Introduction/Background With advances in precision cancer medicine, personalized therapy approaches based on ‘omic’ analyses are being investigated. We present a patient with treatment refractory, metastatic ovarian cancer who achieved dramatic tumor reduction with a combination matched targeted therapy approach.

Methodology Genomic aberrations were assessed using next-generation sequencing (NGS) from formalin-fixed paraffin embedded surgical tumor tissue (315 genes) (Foundation Medicine). Estrogen receptor (ER) was evaluated by immunohistochemistry (IHC). Patient was consented to our institutional Profile-Related Evidence Determining Individualized Cancer Therapy study (NCT02478931).

Results A-40-year-old with serous papillary ovarian cancer presented after progression on 4 lines of systemic treatment. Evaluation with NGS from her initial surgery revealed only a single alteration, in KRAS G12V. In addition, IHC showed strong positivity for ER. Based on these findings, she was treated with trametinib (MEK inhibitor for KRAS alteration) and tamoxifen (estrogen receptor modulator for positive ER expression.) However, serial images showed gradual progression and the therapy was discontinued after 5 months. The patient was subsequently started on monotherapy with letrozole; however, after 3 months of treatment, the tumor progressed. Letroizole was continued and trametinib was restarted. The patient had a prompt and dramatic response (>50% tumor reduction per RECIST 1.1) with a precipitous decline in CA125 (fall to 243 U/ml from >15,000 U/ml at the time of reintroduction of tarmetenib). Treatment is ongoing 11+ months.

Conclusion We report a patient with recurrent ovarian cancer with KRAS alteration and positive ER expression who demonstrated a remarkable response to combination therapy with a MEK inhibitor and aromatase inhibitor after failing treatment with the same MEK inhibitor in combination with a SERM. The current case suggests that different hormone modulators may have divergent effects and that selection of specific combination therapies for potentially pharmacologically tractable alterations can be effective.

Disclosure Shumei Kato serves as a consultant for Foundation Medicine. Razelle Kurzrock receives research funding from Genentech, Incyte, Merck, Serono, Pfizer, Sequenom, Foundation Medicine, Grifols, and Guardant, as well as consultant fees from Loxo, X Biotech, NeoMed, and Actuate Therapeutics, speaker fees from Roche, and an ownership interest in IDby DNA and Curematch Inc. Barbara Parker receives research funding from Novartis, Genentech, Pizer, and Oncoternal Inc. This work was supported in part by Foundation Medicine, the Joan and Irwin Jacobs Fund philanthropic fund; and by National Cancer Institute at the National Institutes of Health [grant P30 CA023100 (Razelle Kurzrock,].

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