Eleftheria Kalogera

A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies

Abstract Purpose: AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared with sequential treatment with ABX then BEV. Given individual drug activity, we investigated the safety and toxicity of AB160 in patients with gynecologic cancers. Patients and Methods: A 3+3 phase I trial was conducted with three potential dose levels in patients with previously treated endometrial, cervical, and platinum-resistant ovarian cancer to ascertain the recommended phase II dose (RP2D). AB160 was administered intravenously on days 1, 8, and 15 of a 28-day cycle (ABX 75–175 mg/m2, BEV 30–70 mg/m2). Pharmacokinetic analyses were performed. Results: No dose-limiting toxicities (DLT) were seen among the three dose levels tested. Grade 3/4 toxicities included neutropenia, thromboembolic events, and leukopenia. DL2 (ABX 150 mg/m2, BEV 60 mg/m2) was chosen as the RP2D. Seven of the 19 patients with measurable disease (36.8%) had confirmed partial responses (95% confidence interval, 16.3%–61.6%). Pharmacokinetic analyses demonstrated that AB160 allowed 50% higher paclitaxel dosing and that paclitaxel clearance mirrored that of therapeutic antibodies. Conclusions: The safety profile and clinical activity of AB160 supports further clinical testing in patients with gynecologic cancers; the RP2D is DL2 (ABX 150 mg/m2, BEV 60 mg/m2).

Outcomes and patient perspectives following implementation of tiered opioid prescription guidelines in gynecologic surgery

To report the impact of implementing standardized guidelines for opioid prescriptions after gynecologic surgery and describe patient perspectives before and after implementation for those undergoing laparotomy for ovarian cancer. Patients undergoing gynecologic surgery between October 2017 and May 2018 were prescribed opioids at discharge using tiered guidelines; prescriptions were compared to consecutive historical controls (March 2017-October 2017). A subset of ovarian cancer laparotomy patients were surveyed regarding postoperative opioid consumption and patient experience. A total of 620 women in the tiered guideline cohort were compared with 599 historical controls. Following implementation, 95.8% of prescriptions met guidelines. Median milligram morphine equivalents (MME) prescribed decreased from 150 to 75 (p ≤ 0.001) with no change in opioid refills (7.7 vs 6.9%, p = 0.62). In surveyed ovarian cancer patients, 100% of tiered guideline patients and 92% of historical controls felt satisfied with pain control (p = 0.24), despite a 50% reduction in prescribed MME and 14.6% receiving no opioids at discharge (p = 0.002). The median (IQR) MME consumed after discharge was 15 (0, 75) in tiered guideline patients vs. 24 (0, 135) in historical controls, and 38.2% and 42.4% consumed no opioids, respectively. Mean time between surgery and opioid use cessation was <1 week in both groups; patients' perceptions of opioid prescription appropriateness did not change (p = 0.49). More than 75% of patients kept their remaining opioids rather than dispose of them. Reducing prescribed opioids after gynecologic surgery using tiered guidelines did not increase opioid refills or worsen patients' perceptions of postoperative pain. Even after laparotomy, very little opioids were required over a short duration after dismissal. Infrequent disposal of leftover opioids highlights the need to avoid over-prescribing.