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Low-Grade Serous Ovarian Carcinoma

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Relevant Study Summaries

GOG 281: Trametinib in recurrent low-grade serous ovarian cancer
Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer.
GYOEDU PlusShitanshu Uppal
MILO/ENGOT-ov11: Binimetinib in Recurrent Low-Grade Serous
In low-grade serous ovarian cancer, Binimetinib did not significantly improve PFS compared to standard of care chemotherapy.
GYOEDU PlusShitanshu Uppal

In case someone asks why MILO was negative while GOG 281 was positive. The GOG 281 discussion addresses this question. Here are the summary points:

  1. Patient Population: The GOG 281/LOGS trial included patients who were more heavily pre-treated compared to the MILO/ENGOT-OV11 trial. Nearly half of the GOG 281/LOGS trial patients had received three or more previous treatment regimens, which might have made the control arm less effective than a less heavily pre-treated population in the MILO/ENGOT-ov11 trial.
  2. Standard-of-Care Comparison: The control group in the GOG 281/LOGS trial included five standard-of-care treatment options (paclitaxel, pegylated liposomal doxorubicin, topotecan, letrozole, and tamoxifen), which provided a broad comparison against trametinib. The MILO/ENGOT-ov11 trial had a more limited set of chemotherapy options, which could have influenced the observed outcomes.
  3. Drug Efficacy: Trametinib, the drug used in the GOG 281/LOGS trial, is a more potent MEK inhibitor than binimetinib, which was used in the MILO/ENGOT-ov11 trial. Preclinical studies suggest trametinib's increased potency could translate into greater clinical efficacy.
  4. Trial Design and Expectations: The control arm in the MILO/ENGOT-ov11 study performed better than expected, with a median PFS of 10.6 months, which was higher than anticipated. This could have reduced the observable difference between the experimental and control arms. In contrast, the GOG 281/LOGS trial had more consistent results with the expected outcomes, making the benefit of trametinib more apparent.
  5. Mutation Status: Both studies highlighted the significance of the MAPK pathway mutations (KRAS, BRAF, NRAS). Trametinib's positive result was observed regardless of mutation status, while the MILO/ENGOT-ov11 study noted an association between binimetinib efficacy and KRAS mutations in a post hoc analysis.

Just Read the Abstract

MITO-22

Effect of bevacizumab in advanced low grade serous ovarian cancer: Data from the MITO 22 trial - PubMed
Our study suggests that Bev might be effective in LGSOC both at diagnosis and at the time of relapse. These data warrants further studies.
PubMedLucia Musacchio
  • Bev+CT improved median PFS to 47.86 months vs. 22.63 months with CT alone in first-line treatment.
  • In recurrence, Bev+CT resulted in a median PFS of 37.1 months vs. 11.22 months with CT alone.
  • In recurrence, 38.5% of patients on Bev+CT achieved complete response (CR) and 53.8% partial response (PR); CT alone had 10.3% CR and 31% PR.
  • Complete cytoreductive surgery showed better outcomes with Bev, with PFS not reached for no residual tumor vs. 10 months with residual tumor.

PARAGON Trial

PARAGON: A Phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors - PubMed
Anastrozole was associated with a CBR of 61% of patients with recurrent ER-positive and/or PR-positive LGOC or SBOT for at least 6 months with acceptable toxicity.
PubMedMonica Tang

Clinical Benefit Rate - 64% at 3 months; 61% at 6 months

Median Duration of Response - 10 months

Median PFS - 11 months

Review Papers

Download and copy Table 2 in your notes for reference

Effect of bevacizumab in advanced low grade serous ovarian cancer: Data from the MITO 22 trial - PubMed
Our study suggests that Bev might be effective in LGSOC both at diagnosis and at the time of relapse. These data warrants further studies.
PubMedLucia Musacchio

Read this one only if you are curious about upcoming trials and studies. Otherwise, skip this one!!

Novel therapeutics in low-grade serous ovarian cancer - PubMed
Low-grade serous ovarian cancer is a rare subtype of epithelial ovarian cancer clinically characterized by younger age at diagnosis, relative chemoresistance, and prolonged survival compared with its high-grade serous counterpart. It is molecularly characterized by estrogen and progesterone receptor …
PubMedLauren Cobb