Background
Randomized, multicenter, open-label phase 2 (NCT01367002); updated OS analysis. N=61 randomized (58 evaluable). Advanced (stage III-IV) or recurrent HER2/neu-positive uterine serous carcinoma. ~30% of USC overexpress HER2. Median follow-up 25.9 mo.
Results
Interventions and follow up: Arm A: carboplatin + paclitaxel ×6 cycles (control).
Arm B: carboplatin + paclitaxel ×6 cycles + IV trastuzumab, then maintenance trastuzumab until progression/toxicity.
Randomization: 1:1.
Primary endpoint: progression-free survival; OS and toxicity secondary.
mFollow up: 25.9 mo.
Results: PFS: 12.9 (Arm B) vs 8.0 mo (Arm A), HR 0.46, 90% CI 0.28–0.76, P=.005.
PFS, stage III-IV upfront: 17.7 vs 9.3 mo, HR 0.44, 90% CI 0.23–0.83, P=.015.
PFS, recurrent: 9.2 vs 7.0 mo, HR 0.12, 90% CI 0.03–0.48, P=.004.
OS: 29.6 vs 24.4 mo, HR 0.58, 90% CI 0.34–0.99, P=.046.
OS, stage III-IV: not reached vs 24.4 mo, HR 0.49, 90% CI 0.25–0.97, P=.041.
Arm B: carboplatin + paclitaxel ×6 cycles + IV trastuzumab, then maintenance trastuzumab until progression/toxicity.
Randomization: 1:1.
Primary endpoint: progression-free survival; OS and toxicity secondary.
mFollow up: 25.9 mo.
Results: PFS: 12.9 (Arm B) vs 8.0 mo (Arm A), HR 0.46, 90% CI 0.28–0.76, P=.005.
PFS, stage III-IV upfront: 17.7 vs 9.3 mo, HR 0.44, 90% CI 0.23–0.83, P=.015.
PFS, recurrent: 9.2 vs 7.0 mo, HR 0.12, 90% CI 0.03–0.48, P=.004.
OS: 29.6 vs 24.4 mo, HR 0.58, 90% CI 0.34–0.99, P=.046.
OS, stage III-IV: not reached vs 24.4 mo, HR 0.49, 90% CI 0.25–0.97, P=.041.
Adverse events
Overall: toxicity not significantly different between arms; no excess with trastuzumab.
Cardiac: no clinically significant trastuzumab-attributable cardiotoxicity.
Detail: grade ≥3 rates NR in this updated report.
Cardiac: no clinically significant trastuzumab-attributable cardiotoxicity.
Detail: grade ≥3 rates NR in this updated report.
Conclusions
Adding trastuzumab to carboplatin/paclitaxel improved PFS and OS in advanced/recurrent HER2/neu-positive uterine serous carcinoma, with greatest benefit in stage III-IV disease treated upfront and no added toxicity.
Key Limitations
Small phase 2 sample (61 randomized) limits precision, reflected in wide 90% confidence intervals. Open-label design. Most striking benefit driven by predefined subgroups (notably stage III-IV upfront disease), so subgroup estimates warrant cautious interpretation. Confirmation in a larger randomized trial was needed.
Clinical Context
No specific FDA/EMA approval (trastuzumab used off-label here); this trial made carboplatin-paclitaxel-trastuzumab a widely adopted option for advanced/recurrent HER2-positive USC, with greatest benefit when given upfront for stage III-IV disease. ASCO/ESMO endorse HER2 testing (IHC with reflex FISH) in serous histology. Confirmatory phase 3 NRG-GY026 launched to validate anti-HER2 therapy.