MD Anderson researchers highlight advances in gynecologic cancer treatments

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This is Pamela Soliman, M.D.
This is David  Gershenson, M.D.
This is Denise Renee Nebgen, M.D., Ph.D.

ABSTRACTS: 5506, 5502, 1506 Advances that could change gynecologic cancer standard-of-care treatments are the centerpiece of key studies being presented by researchers from The University of Texas MD Anderson Cancer Center’s Department of Gynecologic Oncology and Reproductive Medicine at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Combining Targeted Cancer Therapies Everolimus and Letrozole with Diabetes Drug Metformin Shows Clinical Benefits for Advanced/Recurrent Endometrial Cancer

Adding metformin, an anti-diabetes medication, to the combination of targeted cancer therapies everolimus and letrozole results in a 67 percent clinical benefit rate in patients with recurrent, previously treated endometrioid endometrial cancer (EEC).

MD Anderson researchers have enrolled 58 patients in a Phase II prospective trial that builds on promising results in prior studies that combined everoliumus and letrozole to treat recurrent EEC, which typically has a low (10-20 percent) response rate to chemotherapy – the current standard of care. This study is based on preclinical data and experience from a previous clinical trial that suggested metformin may enhance patients’ response to the targeted cancer drugs.

To date, 48 patients were evaluated for response to the three-part combination therapy and showed a 66.7 percent clinical benefit rate, indicating they had either a partial or complete response or their disease was stable. The best overall responses observed to date are 29 percent partial response and 38 percent rate of stable disease after a median of six 28-day cycles of the drugs (delivered every eight weeks, unless the disease progresses or toxicity is observed). One patient showed complete response, to date.

“Though more work needs to be done to better understand exactly how metformin works at a molecular level across various disease sites, this work adds to a growing body of research that shows potential benefits for the drug in cancer care,” said principal investigator Pamela Soliman, M.D., associate professor of Gynecologic Oncology and Reproductive Medicine. Future studies will continue to explore potential therapy combinations that may improve outcomes for these patients, who currently face low survival rates.

Soliman will present these findings Sunday, June 5, in an oral abstract session on gynecologic cancer (9:45 AM to 12:45 PM CT).

Hormonal Maintenance Therapy May Improve Survival in Women with Chemo-resistant Low-grade Serous Carcinoma of the Ovary/Peritoneum

For women with a rare subtype of epithelial ovarian cancer, known as low-grade serous carcinoma (LGSC), hormone maintenance therapy (HMT) may significantly improve survival.

In this retrospective cohort study, researchers analyzed data from 204 women with stage 2-4 LGSC treated at MD Anderson between 1981 and 2013 to evaluate the effect of HMT compared with surveillance after surgery and chemotherapy. Women who received HMT (70 patients) showed an average progression-free survival (PFS) of 64.9 months (5.4 years) compared with 27.3 months (2.2 years) for those in the surveillance group (134 patients). Overall survival was 115.7 months (9.6 years) following HMT, versus 98.8 months (8.2 years) for the surveillance group. Further:

40 percent of women who received HMT have not experienced cancer recurrence, compared with just 12 percent of women in the surveillance group.

Among 148 women who showed no evidence of disease following chemotherapy, HMT appears to have resulted in even greater survival: 81.1 vs. 29.9 months (6.7 vs. 2.5 years) PFS; and 191.3 vs. 106.8 months (16 vs 9 years) overall survival.

“Hormonal therapy has shown promising results in reducing cancer recurrence, and there is increasing interest in integrating this approach into first-line therapy,” said principal investigator David Gershenson, M.D., professor of Gynecologic Oncology Reproductive Medicine. “If further research in a clinical setting shows HMT can prevent or delay recurrence of this cancer subtype, it would be practice changing.”

LGSC accounts for just 10 percent of serous carcinomas of the ovary/peritoneum. It is typically diagnosed in younger women, as early as their 40s (however, teenagers and women in their 20s also may be diagnosed), and patients usually present with advanced disease. The cancer is relatively chemo-resistant compared with high-grade serous carcinoma, although chemotherapy remains part of the standard treatment course. Roughly 70 percent of women will experience a recurrence of the cancer at some point, added Gershenson.

Though recruitment for this patient population is challenging given the rarity of the disease, Gershenson noted that a prospective clinical trial should be designed to further test the findings.

Gershenson will present these findings Sunday, June 5, in an oral abstract session on gynecologic cancer (9:45 AM to 12:45 PM CT).

Prophylactic Salpingectomy with Delayed Oophorectomy (PSDO) May Preserve Sexual Function, Prevent Early Onset of Menopause in Women with BRCA Mutations

With mounting evidence suggesting the fallopian tubes are the site of origin for BRCA-associated ovarian malignancies, an MD Anderson feasibility study demonstrated patient acceptance and satisfaction with prophylactic salpingectomy (fallopian tube removal) with delayed oophorectomy (ovary removal). The study also showed a trend toward preservation of sexual function and absence of menopausal symptoms with PSDO.

The prospective study enrolled 44 patients ages 30 to 47 who chose one of three options: screening (12 women); risk-reducing salpingo-oophorectomy (RRSO; 12 women); or PSDO (20 women). Screening and PSDO patients were seen at six-month intervals for CA-125 and transvaginal ultrasound screening. At baseline and 12 months, researchers administered questionnaires on quality of life, sexuality and menopause.

Researchers observed worsening scores on the questionnaires in the RRSO group, while scores for the PSDO arm remained unchanged.

“As BRCA testing becomes more common, additional women are being blindsided in their 20s and 30s – the prime of their reproductive life – by the knowledge that they carry a potentially life-threatening genetic mutation,” said principal investigator Denise Renee Nebgen, M.D., Ph.D., associate professor of Gynecologic Oncology Reproductive Medicine. “Oophorectomy can dramatically reduce their risk of cancer, but it comes at a cost. Salpingectomy is not yet the standard of care, but it’s an evolving alternative.”

Building on this study, MD Anderson is leading a Stand Up to Cancer Ovarian Cancer Dream Team-funded multi-site clinical trial investigating fallopian tube removal and RRSO in 300 women with BRCA and additional mutations that elevate their risk of ovarian cancer.

Nebgen will present these findings Tuesday, June 7, in an oral abstract session on cancer prevention, hereditary genetics and epidemiology (8:00 AM to 11:00 AM CT).

Source: University of Texas M. D. Anderson Cancer Center

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