Dr Chase on the FDA Approval of Dostarlimab Plus Chemotherapy in Endometrial Cancer

Dana M. Chase, MD, associate professor, obstetrics and gynecology, Division of Gynecologic Oncology, the University of California, Los Angeles, discusses the significance of the FDA approval of dostarlimab-gxly (Jemperli) plus chemotherapy for patients with primary advanced or recurrent endometrial cancer.

the FDA approved dostarlimab in combination with carboplatin and paclitaxel

, followed by single-agent dostarlimab maintenance therapy, for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This approval expanded 

 for adult patients with mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) primary advanced or recurrent endometrial cancer.

The expanded regulatory decision was supported by findings from part 1 of the phase 3 RUBY trial (NCT03981796), in which patients in the overall population who received the dostarlimab combination (n = 245) achieved a median overall survival of 44.6 months (95% CI, 32.6-not reached) vs 28.2 months (95% CI, 22.1-35.6) with placebo (HR, 0.69; 95% CI, 0.54-0.89; 1-sided 

 = .002). Furthermore, the median progression-free survival was 11.8 months (95% CI, 9.6-17.1) in the dostarlimab arm compared with 7.9 months (95% CI, 7.6-9.5) in the placebo arm (HR, 0.64; 95% CI, 0.51-0.80; 1-sided 

The most common adverse effects occurring in at least 20% of patients who received the dostarlimab regimen included anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelet count, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection, and vomiting. 

Endometrial cancers are categorized according to their molecular subtype, and some therapies are more effective in certain patient subgroups based on the disease’s molecular classification, Chase begins. Historically, the use of many endometrial cancer therapies has been limited to specific patient subgroups based on the presence of a biomarker or other molecular classification, she says. However, this expanded indication for dostarlimab widens the eligibility criteria for this agent beyond patients with dMMR/MSI-H disease, Chase concludes.

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Dana M. Chase, MD, discusses the FDA approval of dostarlimab plus chemotherapy for patients with primary advanced or recurrent endometrial cancer.

Dana Chase, MD, FACOG, assistant professor at the University of Arizona College of Medicine Phoenix and Creighton University at St. Joseph’s Hospital and Medical Center, Arizona Oncology, The US Oncology Network, discusses the use of niraparib (Zejula) as frontline maintenance therapy in ovarian cancer.

The phase III PRIMA trial is one of the first trials to demonstrate the efficacy of PARP inhibitors, specifically niraparib, in frontline maintenance therapy, says Chase. In December 2018, olaparib (Lynparza) was approved by the FDA for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic 

-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. However, in the PRIMA trial, investigators administered niraparib to all comers, which is new and unique, according to Chase.

Previously, the standard of care for patients with ovarian cancer who did not have a 

mutation was chemotherapy followed by surveillance, says Chase. Other patients received bevacizumab (Avastin) with chemotherapy and continued bevacizumab as frontline maintenance. Until PRIMA, there was no access to use PARP inhibitor therapy in the all-comer patient population, concludes Chase.

Dana Chase, MD, discusses niraparib as frontline maintenance therapy in ovarian cancer.

Dr. Chase on Niraparib as Frontline Maintenance Therapy in Ovarian Cancer

Dana Chase, MD, gynecologic oncologist, Arizona Oncology, discusses the standard of care for the treatment of patients with uterine leiomyosarcoma.

If disease is recurrent or advanced upon presentation, it is standard to give systemic treatment, says Chase. The standard treatment for those patients include chemotherapy. There are currently several FDA-approved options that can be used in that setting, per the guidelines.

Traditionally, gynecologic oncologists used docetaxel and gemcitabine. That has really been the go-to regimen for these tumors, says Chase. Recent data suggests that single-agent doxorubicin or doxorubicin with olaratumab (Lartruvo) are good alternatives. Chase states that doxorubicin with olaratumab could potentially be superior to docetaxel and gemcitabine, though physicians do not have data on that yet. These data are expected within the next year or 2, says Chase.

Dr. Chase on the Standard of Care for Uterine Leiomyosarcoma

Dana Chase, MD, gynecologic oncologist, Arizona Oncology, discusses the presentation of uterine sarcomas.

Uterine sarcomas are very rare in the gynecologic oncology world. Only about 2% to 4% of uterine cancers are uterine sarcomas, Chase explains. Physicians estimate that a gynecologic oncologist has approximately 2 or 3 active patients in their practice, and most uterine sarcomas present in the form of leiomyosarcomas. Carcinoid sarcomas are the most common type of uterine sarcomas, but they are classified as more traditional endometrial cancers.

After that, uterine leiomyosarcomas are the next most common type of uterine sarcoma. Those patients typically don’t present with uterine bleeding. They may have been found to have this tumor because they were having a hysterectomy for fibroids. In the metastatic setting, patients may have been found to have abdominal pain or shortness of breath and received a biopsy that revealed uterine leiomyosarcoma. Often in the early-stage setting, the gynecologic oncologist meets with the patient after they were operated on by a gynecologist. From that point, the physician has to determine whether to administer chemotherapy or observation.

Dana Chase, MD

Articles

Dr Chase on the FDA Approval of Dostarlimab Plus Chemotherapy in Endometrial Cancer

Dr. Chase on Niraparib as Frontline Maintenance Therapy in Ovarian Cancer

Dr. Chase on the Standard of Care for Uterine Leiomyosarcoma

Dr. Chase on the Presentation of Uterine Sarcomas