A phase 2 feasibility study of nab-paclitaxel and carboplatin in epithelial carcinoma of the uterus

We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. Patients with early-stage, high-risk, advanced primar...

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Published in:Gynecologic oncology 2024-11, Vol.190, p.209-214
Main Authors: Pothuri, B., Sawaged, Z., Karpel, H.C., Li, X., Lee, J., Musa, F., Lutz, K., Reese, E., Blank, S.V., Boyd, L.R., Curtin, J.P., Goldberg, J.D., Muggia, F.M.
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Language:English
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Summary:We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. From 08/2016–03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months. The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC. •Dose-dense nab-paclitaxel on day 1, 8 with day 1 carboplatin every 3 weeks is feasible (6-cycle completion rate of 82.6%).•In advanced/recurrent cases, median progression free survival was 23.2 months (95% CI: 12.1, not reached).•The regimen had tolerable toxicity, with 61% with grade 1 neuropathy and no patients with grade 3 or 4 neuropathy.•Nab-paclitaxel can be an acceptable taxol replacement for regimens with immunotherapy to avoid use of concomitant steroids.
ISSN:0090-8258
1095-6859
1095-6859
DOI:10.1016/j.ygyno.2024.07.682