Amanda Nickles Fader, MD, vice chair, Gynecologic Surgical Operations, Johns Hopkins Health System, professor of gynecology and obstetrics, Johns Hopkins Medicine, discusses the randomized, phase 3 NRG-GY019 trial (NCT04095364) evaluating letrozole (Femara) with or without paclitaxel and carboplatin in patients with stage II to IV primary low-grade serous carcinoma of the ovary or peritoneum.

A previous joint retrospective study with the Cleveland Clinic and Johns Hopkins Medicine evaluated the omission of chemotherapy in 27 patients with advanced low-grade serous ovarian carcinoma, who received adjuvant hormonal therapy alone following primary cytoreductive surgery. At a median follow-up of 41 months, only 22.2% of patients developed tumor recurrence, and 2 patients died of disease. The median progression-free survival (PFS) and overall survival (OS) was not yet reached, and the 3-year PFS and OS rates were 79.0% and 92.6%, respectively. Among the 27 patients, letrozole was given to 55.5%.

These findings helped lead to the inception of the randomized, two-arm NRG-GY019 trial that will evaluate patients with stage II to IV low-grade serous ovarian carcinoma. Patients will be randomly assigned to receive carboplatin and paclitaxel, followed by letrozole maintenance therapy in the absence of progressive disease or unacceptable toxicity, or letrozole alone.

Fader notes that this may be the first ovarian cancer trial in the advanced stage setting that does not include chemotherapy in one of the treatment arms. This study could help understand whether giving letrozole alone could produce efficacy benefits compared with its use in combination with paclitaxel/carboplatin for patients with low-grade serous ovarian carcinoma, Fader concludes.

Videos

Amanda Nickles Fader, MD, discusses the randomized, phase 3 NRG-GY019 trial evaluating letrozole with or without paclitaxel and carboplatin in patients with stage II to IV primary low-grade serous carcinoma of the ovary or peritoneum.

Dr Fader on Letrozole With or Without Paclitaxel and Carboplatin in Ovarian Serous Carcinoma

Amanda Nickles Fader, MD, an associate professor of Gynecology and Obstetrics, vice chair of Gynecologic Surgical Operations, director of the Kelly Gynecologic Oncology Service, director of the Center for Rare Gynecologic Cancers, at The Johns Hopkins Hospital, and director of the F.J. Montz Fellowship Program in Gynecologic Oncology at Johns Hopkins Medicine, discusses the utility of trastuzumab (Herceptin) plus chemotherapy in HER2-positive uterine serous carcinoma.  

Results from a randomized phase II clinical trial (NCT01367002) demonstrated an improvement in progression-free survival (PFS) and overall survival (OS) with the addition of trastuzumab to carboplatin/paclitaxel in patients with advanced or recurrent, HER2-positive uterine serous carcinoma. 

Findings revealed that patients with stage III/IV disease who received the triplet up front derived the greatest benefit in OS and PFS. At a median follow-up of 25.9 months, the median OS had not been reached compared with 25.4 months.  

 There are many theories as to why the patients who received the triplet up front tended to respond better than those who received it after recurrence, explains Fader. Women with recurrent disease had already been pretreated with carboplatin/paclitaxel, so they could have developed resistance to the regimen, says Fader. Moreover, data show that carboplatin/paclitaxel is not as effective in the recurrent setting compared with the upfront setting. 

While additional research is needed, these findings suggest that the addition of trastuzumab is not potent enough to overcome potential resistance to cytotoxic chemotherapy, concludes Fader.

Amanda Nickles Fader, MD, discusses the utility of trastuzumab plus chemotherapy in HER2-positive uterine serous carcinoma.

Dr. Fader on Trastuzumab/Chemo in HER2+ Uterine Serous Carcinoma

Amanda Nickles Fader, MD, an associate professor of Gynecology and Obstetrics, vice chair of Gynecologic Surgical Operations, director of the Kelly Gynecologic Oncology Service, director of the Center for Rare Gynecologic Cancers, at The Johns Hopkins Hospital, and director of the F.J. Montz Fellowship Program in Gynecologic Oncology at Johns Hopkins Medicine, discusses the rationale for utilizing HER2/neu as a target in uterine serous carcinoma.

As in breast cancer, HER2/neu is commonly overexpressed in select uterine cancers including uterine serous carcinoma, says Fader.

Though uterine serous carcinoma is a rare subtype of uterine cancer, a randomized phase II trial (NCT01367002) showed that up to 30% of the study population had HER2/neu overexpression, says Fader.

The study examined the efficacy of adding trastuzumab (Herceptin) to carboplatin/paclitaxel in patients with advanced or recurrent uterine serous carcinoma that overexpresses HER2/neu.

Findings from the study demonstrated that the addition of trastuzumab to chemotherapy improved progression-free survival and overall survival for patients compared with chemotherapy alone.

Amanda Nickles Fader, MD, discusses the rationale for utilizing HER2/neu as a target in uterine serous carcinoma.

Dr. Fader on the Rationale for Targeting HER2/neu in Uterine Serous Carcinoma

Amanda Nickles Fader, MD, an associate professor of Gynecology and Obstetrics, vice chair of Gynecologic Surgical Operations, director of the Kelly Gynecologic Oncology Service, director of the Center for Rare Gynecologic Cancers, at The Johns Hopkins Hospital, and director of the F.J. Montz Fellowship Program in Gynecologic Oncology at Johns Hopkins Medicine, discusses findings from a randomized phase II trial examining the efficacy of adding trastuzumab (Herceptin) to carboplatin/paclitaxel in patients with advanced or recurrent uterine serous carcinomas that overexpress HER2/neu.

After a median follow-up of 25.9 months, results from the trial showed that the addition of trastuzumab to carboplatin/paclitaxel led to improved PFS versus patients who received carboplatin/paclitaxel alone, at 12.9 months versus 8.0 months, explains Fader. The biggest difference was observed in patients with stage III/IV disease who were treated up front, adds Fader; for those patients, the PFS in the trastuzumab arm was 17.7 months versus 9.2 months in the control arm, says Fader.

The trastuzumab arm also experienced an improved overall survival (OS) benefit, at 29.6 months versus 24.4 months in the control group. For patients with stage III/IV disease who were treated up front with the trastuzumab-containing regimen, the median OS has not yet been reached, according to Fader.

Last year, the National Comprehensive Cancer Network guidelines for uterine cancer recognized the addition of trastuzumab as a preferred treatment regimen in patients with HER2-overexpressed uterine serous carcinomas, concludes Fader.

View more from the 2020 SGO Annual Meeting

Amanda Nickles Fader, MD, discusses findings from a randomized phase II trial examining the efficacy of adding trastuzumab to carboplatin/paclitaxel in patients with advanced or recurrent uterine serous carcinomas that overexpress HER2/neu.

Amanda Nickles Fader, MD

Articles

Dr Fader on Letrozole With or Without Paclitaxel and Carboplatin in Ovarian Serous Carcinoma

Dr. Fader on Trastuzumab/Chemo in HER2+ Uterine Serous Carcinoma

Dr. Fader on the Rationale for Targeting HER2/neu in Uterine Serous Carcinoma

Dr. Fader on Adding Trastuzumab to Chemo in HER2+ Uterine Serous Carcinoma