Trastuzumab Improves PFS in Rare Endometrial Cancer in Phase 2 Trial

New research demonstrates that adding trastuzumab to chemotherapy has benefits for patients with uterine serous carcinoma (USC), a rare, aggressive variant of endometrial cancer. In a multicenter, randomized, phase 2 trial comparing a chemotherapy regimen of carboplatin and paclitaxel with carboplatin and paclitaxel plus trastuzumab, Amanda Fader, MD, and colleagues demonstrated that trastuzumab increased progression-free survival (PFS) in patients with USC.

While USC—which has a mutational profile including dysregulation of HER2—only comprises 3% to 10% of all cases of endometrial cancer, USC accounts for a disproportionately high number of deaths. Five-year survival for patients with USC is approximately 41%, versus 75% among women with grade 3 endometerioid tumors. Because of USC’s rarity, optimal management of this rare cancer remains controversial.

The study, funded by Genentech—Roche and newly published in the Journal of Clinical Oncology, was conducted from August 2011 to March 2017. The trial enrolled patients with primary advanced stage III or stage IV or recurrent HER2-positive USC who were randomly assigned to either the chemotherapy arm (n = 28) or the chemotherapy plus trastuzumab arm (n = 30). The study’s primary endpoint was PFS. Patients in the chemotherapy arm completed a total of 156 (range, 1 to 8) cycles of treatment, and patients in the chemotherapy plus trastuzumab completed a total of 178 (range, 4 to 9) cycles.

At the time of the analysis, after a median 10 months of follow-up, 58 response-evaluable patients experienced 40 PFS-related events (39 progressions and 1 fatal thromboembolism). Among the patients who remained alive and progression-free, 5 were in the chemotherapy group, and 13 were in the chemotherapy plus trastuzumab group. PFS was 8.0 months in the chemotherapy group and 12.6 months in the trastuzumab group (Hazard ratio 0.44; 90% CI, 0.26-0.76; P = .005). Final overall survival data are forthcoming.

“The fact that these tumors grow rapidly, but also have a propensity to spread to lymph nodes and other organs very early, is a double whammy for women…Even an improvement of a few months may be quite meaningful for women with these cancers,” said Fader in a statement, adding that larger studies of the drug combination will be needed to confirm these findings.

Reference

Fader AN, Roque DM, Siegel E, et al. Randomized phase 3 trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. [Published online March 27, 2018.] J Clin Oncol. doi: 10.1200/JCO.2017.76.5966.