Add-On Metformin No assist with superior endometrial most cancers


A Phase II / III study found that women with relapsed or late-stage endometrial cancer, including metformin as part of standard chemotherapy, did not offer any additional benefit.

In the study of 450 patients who all received carboplatin plus paclitaxel, the median overall survival (OS) in the metformin group was 34.6 months compared to 30.4 months in the placebo group, a non-significant benefit (HR 0.89, 95%) CI 0.68-1.16, P = 0.185), reported Dr. Victoria Bae-Jump from the University of North Carolina at Chapel Hill.

The results presented at the Society of Gynecologic Oncology (SGO) annual webinar series also showed no significant progression-free survival benefit (PFS) for metformin versus placebo (9.0 vs. 8.5 months, HR 0.89, 95% CI 0.71-). 1.10).

“Paclitaxel-carboplatin-metformin was well tolerated with no unexpected serious toxicities – the metformin arm was slightly less hyperglycemic,” said Bae-Jump. “However, adding metformin to paclitaxel carboplatin did not significantly improve progression-free survival or overall survival.”

The response rates between the metformin and placebo arms were similar (62% versus 60%).

Epidemiological data suggest that metformin may lower the risk of cancer (including the endometrium) in patients taking the drug for diabetes, and preclinical studies have reported antitumor activity. A recent randomized study of metformin in metastatic prostate cancer also showed no significant survival benefit.

The results of the current study – NRG Oncology / GOG 286B – also confirm the racial differences in endometrial cancer, as black women responded to treatment far less often than whites (43% versus 64%) and the black race was significantly associated with poorer PFS (8, 4 vs 9.0 months; HR 1.50, 95% CI 1.10-2.02).

“Even more alarming was the difference in overall survival between the black and white women in the study,” said Bae-Jump, pointing to a median OS of 18.3 months for black women versus 36.9 months for white women (HR 2, 03, 95%) CI 1.43-2.89).

“As expected, there was a greater proportion of African-American patients with serous tumors than white women, but despite similar response rates between serous and endometrioid histology, African-American women’s response rates were worse compared to white women.” said SGO panelist Melissa Geller of the University of Minnesota at Minneapolis.

She said the researchers are targeting 800 genes from the tumors of the 61 African American women participating in the study, and that these “critical data” could shed light on the observed differences in response and treatment outcomes.

From 2014 to 2018, 469 women with recurrent endometrial cancer or stage III / IV endometrial cancer received chemotherapy plus metformin or placebo in the phase II / III study. The primary endpoints of the study were PFS for phase II and OS for phase III.

About 80% of the study cohort were white and 13% black. The study was stratified by BMI, but this was not an indication of the OS in the metformin arm. Overall, the study found higher obesity rates among black (64%) versus white (48%) women.

The researchers also examined the results of the expression of metformin transporter proteins (MATE2 / OCT3) and phosphorylated IGF1-R by patients, but even these did not predict survival results.

“The translational science of metformin continues to evolve and further studies in early-stage endometrial cancer with metformin are being conducted to determine what role this drug might play,” said Geller.

In the control arm, patients received intravenous paclitaxel (175 mg / m2) plus carboplatin (target AUC 5) every 3 weeks for up to 10 cycles plus maintenance placebo until disease progression or unacceptable toxicity. In the study arm, patients received the same chemotherapy regimen plus oral metformin (850 mg once daily) as maintenance therapy.

Baseline characteristics were well balanced between the two arms, with more than 70% of women being 60 years or older. Just over 70% had measurable disease, and a majority (57%) received either regimen as primary treatment.


Bae-Jump announced relevant relationships with NovaTarg, Merck, Oncoceutics, Sphaera, Tesaro, Eisai and Rakuten.

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