Paclitaxel plus carboplatin demonstrated noninferiority to paclitaxel plus ifosfamide and should be a standard treatment for uterine carcinosarcoma, according to results of a phase 3 study published in Journal of Clinical Oncology.

“The better tolerated and more convenient regimen of paclitaxel-carboplatin should be the preferred regimen of choice for gynecologic carcinosarcomas,” Matthew A. Powell, MD, professor of obstetrics and gynecology and chief in the division of and chief gynecologic oncology at Washington University School of Medicine in St. Louis, told Healio.

Background

An estimated 66,570 women in the U.S. received a diagnosis of uterine cancer and another 21,410 received a diagnosis of ovarian cancer in 2021, according to study background. A regimen of paclitaxel and carboplatin has been the standard for epithelial ovarian carcinoma for decades and became the standard for endometrial carcinomas within the last 2 years.

Previous studies showed benefits of the paclitaxel-ifosfamide regimen, but the treatment has drawbacks, according to Powell.

Matthew A. Powell

“The ifosfamide regimen (is associated with) significant toxicity in this often-frail population (and) the 3-day regimen is also very inconvenient for patients and requires growth factor support,” he told Healio. “Also, we learned that molecularly, these cancers are epithelial tumors and not true sarcomas, so perhaps the paclitaxel-carboplatin regimen would be superior.”

Methodology

Powell and colleagues tested the null hypothesis that paclitaxel-carboplatin was inferior to paclitaxel-ifosfamide in an international, open-label study that included 449 adult women with uterine carcinosarcoma. Nearly half (47.9%) had stage III or stage IV disease at enrollment.

Researchers randomly assigned 228 of the women to paclitaxel-carboplatin (median age, 65 years; 65.8% white; 28.9% Black) and 221 to paclitaxel-ifosfamide (median age, 64 years; 60.2% white; 32.6% Black), administered in 3-week cycles for six to 10 cycles.

OS from the date of randomization served as the study’s primary endpoint, with PFS, adverse events, quality of life and neurotoxicity scores as secondary endpoints.

Key findings

Paclitaxel plus carboplatin demonstrated noninferiority to paclitaxel plus ifosfamide. Results showed median OS of 37 months with paclitaxel-carboplatin vs. 29 months with paclitaxel-ifosfamide (HR = 0.87; 90% CI, 0.7-1.07) and median PFS of 16 months vs. 12 months (HR = 0.735; 95% CI, 0.58-0.93).

Researchers observed similar toxicities between the groups, with more hematologic toxicities in the paclitaxel-carboplatin group and more confusion and genitourinary hemorrhaging in the paclitaxel-ifosfamide group.

Among a separate cohort of 90 women with ovarian carcinosarcoma, researchers reported longer OS (30 months vs. 25 months) and PFS (15 months vs. 10 months) with paclitaxel and carboplatin, but the differences did not reach statistical significance.

Implications

The findings establish paclitaxel plus carboplatin as a new standard regimen for uterine carcinosarcomas of all stages, especially among women with stage III disease, researchers wrote. Future areas of study included identifying and targeting molecular aberrations within the tumors, which should lead to further improvements in treatment, they concluded.