Latest treatment option in uterine cancer

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According to the latest report from the US Centers for Disease Control and Prevention (CDC), the incidence of almost all cancers has declined in the past two decades, while the incidence of uterine cancer has risen. Doctors began to pay attention to this situation and reminded women to pay attention to several key issues of this disease.

According to statistics from the American Cancer Society (ACS), more than 90% of uterine cancers occur in the endometrium, called endometrial cancer. Early endometrial cancer has a good prognosis. According to the US Centers for Disease Control and Prevention, the five-year relative survival rate is estimated to be 80% to 90%. Because uterine cancer can usually be diagnosed early, its most typical symptoms are abnormal bleeding before and after menopause, weight loss and pelvic pain. For advanced metastatic patients, treatment options are very limited.

Recently, the US FDA approved the PD-1 inhibitor Keytruda (pabolizumab) in combination with the oral tyrosine kinase inhibitor Lenvima (Levatinib) to treat patients with specific advanced endometrial cancer. It is worth noting that these patients do not require high microsatellite instability (MSI-H) or mismatch repair defect (dMMR) types. As long as the disease continues to progress after receiving early systemic therapy and cannot receive curative surgery or radiotherapy, this new combination therapy can be accepted.

It must be mentioned that this accelerated approval was approved simultaneously in the United States, Australia and Canada.

The approval is based on the results of a study of 94 patients with endometrial cancer tumors, none of whom are MSI-H or dMMR. In these patients, the total response rate (ORR) was 38.3%, including 10.6% complete response rate (CR) and partial response rate of 27.7%. 69% (n = 25) patients had duration of response (DOR) ≥ 6 months.

“At least 75% of patients with endometrial cancer are not of MSI-H or dMMR type, so the approval of this therapy brings new treatment options and hope to most patients with endometrial cancer.

At present, other research progress of endometrial cancer is also briefly introduced here:

01avelumab (Bavincia monoclonal antibody) combined with talazoparib (tarazopanib )

A trial led by Konstantinopoulos used the immune checkpoint inhibitor avelumab in combination with the PARP inhibitor talazoparib. (Checkpoint inhibitors clear the way for the immune system to attack cancer; PARP inhibitors destroy cancer cells by hindering their ability to repair damaged DNA.) In a previous experiment, avelumab was Patients with “unstable” endometrial cancer are very effective, but are essentially inactive in the more common “microsatellite stable” (MSS) form of disease. The trial will explore whether combining avelumab with PARP inhibitors is more effective in patients with MSS disease.

02pembrolizumab (pabolizumab) combined with mirvetuximab

A test combining the checkpoint inhibitor pembrolizumab with mirvetuximab. (Pembrolizumab targets an immune checkpoint protein called PD-1; mirvetuximab adds antibodies to drug molecules targeting key structures in rapidly dividing cancer cells.) The trial, led by Jennifer Veneris, MD, of the Gynecologic Oncology Project, will examine the combination Effectiveness in patients with MSS endometrial cancer.

03abemaciclib + LY3023414 + hormone therapy

Another trial led by Konstantinopoulos will test the combination of targeted drug abemaciclib + LY3023414 + hormone therapy. (LY3023414 targets a cancer cell enzyme called PI 3 kinase; abemaciclib interferes with a critical phase of the cell cycle.) 70% to 90% of endometrial cancers are fed by estrogen and initially respond to hormone blocking therapy, but ultimately relapse. By adding abemaciclib and LY3023414 (they can touch two parts of the same molecular pathway) for hormone blocking therapy, the researchers hope to overcome the drug resistance problem.

04AZD1775

A trial led by Joyce Liu, MD, MPH, director of clinical research at the Department of Gynecologic Oncology at Dana-Farber, used AZD1775 for patients with high-grade serous uterine cancer that account for 10-15% of endometrial cancer. Such cancers are aggressive and usually recur after standard treatment. The recently opened trial is based on a study led by Dr. Liu and Ursula Matulonis, director of the Dana-Farber Department of Gynecologic Oncology, showing that AZD1775 is active in a patient model with high-grade serous ovarian cancer.

05dostarlimab (TSR-042)

The results of the Phase I / II GARNET trial were recently published, and the overall effective rate of PD-1 inhibitor dostarlimab (TSR-042) for patients with relapsed or advanced endometrial cancer is close to 30%.

In addition, both micro-satellite instability (MSI-H) and micro-satellite stability (MSS) groups are persistent.

Dostarlimab (TSR-042) is a humanized anti-PD-1 monoclonal antibody jointly developed by TESARO and AnaptysBio. It binds to the PD-1 receptor with high affinity, thereby blocking its binding to PD-L1 and PD-L2 ligands.

The results showed that the effective rate of the entire population was 29.6%, the effective rate of the MSI-H patient group was 48.8%, and the effective rate in the MSS cohort was 20.3%. Six patients (2 MSI-H and 4 MSS) had complete remission.

After a median follow-up of 10 months, 89% of patients received treatment> 6 months, and 49% of patients received treatment for> 1 year. In addition, 84% of patients who are effective in treatment are still receiving treatment.

Finally, in 85% of MSI-H responders, the total tumor burden was reduced by ≥50%, and 69% of patients with MSS had a total tumor burden of ≥50%.

Dostarlimab is a new hope for the treatment of endometrial cancer.

The researchers will start further III studies in the second half of 2019. Dostarlimab and chemotherapy will be combined with first-line treatment of endometrial cancer, and we look forward to obtaining promising results soon!

Each trial addresses the shortcomings of standard treatment or problems found in previous new drug trials. For example, the first two trials are aimed at overcoming the current state of poor immunotherapy in patients with MSS disease. The third solves the problem of resistance to hormone therapy, and the fourth targets specific subtypes of endothelial cancer.

To learn more about the latest research progress and the best medication plan for endometrial cancer, only the top cancer experts at home and abroad have rich clinical experience. You can apply for consultation with the following domestic and international authoritative experts to get the best diagnosis and treatment plan.

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