Loprinzi, Charles L.

AbstractBackgroundLow molecular weight heparin (LMWH) is the guideline‐endorsed treatment for cancer‐associated venous thromboembolism (cVTE). Study objectives were to compare the efficacy and safety of rivaroxaban and enoxaparin in cVTE.MethodsUsing a cohort study design, consecutive patients with cVTE (3/1/2013‐7/31/2016), enrolled in the Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry, were compared to contemporary cancer patients receiving enoxaparin. The cumulative incidence of venous thromboembolism (VTE) recurrence, major and clinically relevant non‐major bleeding, and survival were assessed at 3 and 12 months.ResultsNinety‐eight patients received rivaroxaban (51% female, mean age 63 ± 12 years) and 168 enoxaparin (34.5% female, mean age 62 ± 15 years). The most common cancers included gastrointestinal/pancreatic, genitourinary and hematologic cancers. More than half of patients had pulmonary emboli at presentation. More than half had metastases, and two‐thirds were receiving chemotherapy. At 3 months, there were no differences in VTE recurrence (rivaroxaban 1.0% vs enoxaparin 4.2%; P = .15), major bleeding (rivaroxaban 5.1% vs enoxaparin 3.6%; P = .55), or all‐cause mortality (rivaroxaban 4.1% vs enoxaparin 8.9%; P = .14). At 12 months, these outcomes did not differ by treatment strategy.ConclusionThe results of this “real‐world” experience with cVTE suggest that rivaroxaban may offer a safe and effective alternative to LMWH.

219 Background: Dryness, crusting, and bleeding of the nares due to inflammation, termed nasal vestibulitis (NV), is infrequently reported as a side effect of cancer treatments. However, one study described 115 patients who developed NV while undergoing targeted therapies; many were treated with bacitracin ointment (Ruiz et al Sup Care Cancer 2015). Methods: This study surveyed 94 patients regarding the presence of nasal symptoms during cancer treatments. Participants were consented for the study if they had undergone at least 6 weeks of cancer-directed therapy in the Mayo Clinic Chemotherapy Unit. They were asked about types of nasal symptoms, severity, and symptom treatments. A chart review was then conducted to determine documentation of symptoms, the presence of concurrent illnesses, and cancer treatment regimens. Results: Ninety-four patients completed questionnaires, with 41% reporting unpleasant nasal symptoms that they attributed to cancer treatments. Of the symptomatic patients, 46% had dryness, 33% had discomfort, 54% had bleeding, and 46% had scabbing. Average severity was 1.9 on a scale from 1 to 3 (1 = mild, 3 = severe). Symptoms were noted in patients undergoing a variety of cancer treatment regimens, with the highest frequency in patients undergoing a taxane-containing regimen (46%). 62% of patients with symptoms said they reported them to their provider, but only 41% of chart notes (for 16 patients) contained documentation of such, most frequently described as “allergies” or “epistaxis.” Only 10% of symptomatic patients had nasal swabs; all of which were obtained during respiratory illness or pre-op. 49% of patients with nasal symptoms reported treating their symptoms. Antihistamines (7 patients), nasal saline (6 patients), or nasal lubricants (i.e. Vaseline; 7 patients) were used; 2 patients applied bacitracin. 18% of symptomatic patients had providers who recommended treatments, including 2 patients who were thought to have concurrent infection and were treated with antibiotics. Conclusions: NV symptoms are prevalent among oncology patients, but infrequently recorded or treated by providers.

Abstract Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor–positive (ER+) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA-mutant ER+ breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER+ breast cancer. Experimental Design: Potential eligible patients with clinical stage II/III ER+/HER2− breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing. Patients positive for PIK3CA mutation in the tumor were eligible to start MK-2206 (150 mg orally weekly, with prophylactic prednisone) on cycle 1 day 2 (C1D2) and to receive a maximum of four 28-day cycles of combination therapy before surgery. Serial biopsies were collected at preregistration, C1D1 and C1D17. Results: Fifty-one patients preregistered and 16 of 22 with PIK3CA-mutant tumors received study drug. Three patients went off study due to C1D17 Ki67 >10% (n = 2) and toxicity (n = 1). Thirteen patients completed neoadjuvant therapy followed by surgery. No pCRs were observed. Rash was common. MK-2206 did not further suppress cell proliferation and did not induce apoptosis on C1D17 biopsies. Although AKT phosphorylation was reduced, PRAS40 phosphorylation at C1D17 after MK-2206 persisted. One patient acquired an ESR1 mutation at surgery. Conclusions: MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA-mutant ER+ breast cancer and should not be studied further in the target patient population. Clin Cancer Res; 23(22); 6823–32. ©2017 AACR.