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The addition of trastuzumab (Herceptin) to conventional chemotherapy improved overall survival (OS) for women with advanced HER2-overexpressing uterine serous carcinomas, a small randomized trial showed.

Among nearly 60 patients with this rare and aggressive form of endometrial cancer, OS was 24.4 months for women assigned to carboplatin plus paclitaxel and reached 29.6 months for those who also received trastuzumab (HR 0.58, 90% CI 0.34-0.99, P=0.0462), reported Amanda Fader, MD, of Johns Hopkins University in Baltimore.

This survival benefit was restricted to the 41 women with stage III/IV disease, who had a median OS of 25.4 months with chemotherapy alone and an OS not yet reached with additional trastuzumab (HR 0.49, 90% CI 0.25-0.97, P=0.0406), according to the findings presented at the Society of Gynecologic Oncology (SGO) annual meeting webinar series.

"Unfortunately, we did not observe a significant overall survival benefit in the patients with recurrent disease," said Fader, noting that the cohort was underpowered with only 17 patients.

Expanding this subset for future studies would be beneficial to better understand the true potential benefit of HER2-directed therapy in this setting, she added.

The phase II study , showing improved progression-free survival (PFS) with the three-drug combination, findings that led the National Comprehensive Cancer Network to designate carboplatin plus paclitaxel and trastuzumab as a preferred regimen for advanced or recurrent HER2-overexpressed cancers.

"We hope that this additional overall survival data will add to that designation," said Fader.

Updated PFS data presented during the SGO webinar showed a median PFS of 8.0 months for those in the chemotherapy-alone arm versus 12.9 months for women who also received trastuzumab (HR 0.46, 90% CI 0.28-0.76, P=0.005).

And both the stage III/IV and recurrent subgroups showed a PFS advantage with the triplet versus doublet, respectively:

• Stage III/IV: 17.7 vs 9.3 months (HR 0.44, 90% CI 0.23-0.83)
• Recurrent: 17.0 vs 7.0 months (HR 0.12, 90% CI 0.03-0.48)

A subset analysis of 36 patients with stage IIIC/IV disease showed both a PFS benefit with the anti-HER2 approach, as well as an improvement in OS (31.9 vs 21.1 months; HR 0.44, 90% CI 0.22-0.88, P=0.0230).

"These results are quite compelling, but questions certainly remain," said SGO discussant Shannon Westin, MD, MPH, of MD Anderson Cancer Center in Houston. "How can we maximize the results for patients with recurrent cancers?"

She highlighted advancements since the start of the trial, with promising new approaches for targeting the HER2 receptor -- dual anti-HER2 strategies, irreversible tyrosine kinase inhibitors, and novel antibody-drug conjugates.

"It certainly will be interesting to see the impact in uterine serous cancers," said Westin.

From 2011 to 2017, the phase II trial randomized 58 women with recurrent or advanced uterine serous carcinomas to intravenous paclitaxel (175 mg/m²) plus carboplatin (target area under the curve 5 mg·min/mL) every 3 weeks for six cycles with or without trastuzumab (starting dose of 8 mg/kg followed by 6 mg/kg for six cycles, then six additional cycles of maintenance).

Women had a median age of 69 years, though patients in the investigational arm were significantly younger (67 vs 73 years, P=0.006). Overall, about a third were black and roughly two-thirds were white. Among the advanced-stage subgroup, 54% received radiotherapy as their primary treatment and 12% had residual tumor burden following cytoreductive surgery.

Fader noted the trial's small sample size as the primary limitation, pointing out that the trial did not meet the original enrollment targets (100 patients).

"Despite this we still observed significant survival benefit from the addition of trastuzumab to conventional chemotherapy," she said.

An international phase III trial is planned in primary uterine serous carcinoma to confirm the results and investigate additional anti-HER2 therapies.

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