Amanda Nickles Fader, MD

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.

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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.

Author | Amanda Nickles Fader, MD

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