Moynihan, T. J.

9592 Background: Palliative care (PC) is an essential part of the continuum of care for cancer (CA) patients (pts). Little is known about the aggregate characteristics and survival of pts receiving inpatient palliative care consultation (PCC). Methods: We reviewed data prospectively collected on patients seen by the Palliative Care Inpatient Consult Service at Mayo Clinic - Rochester from 2003–2008. Demographics, consult characteristics, and survival were analyzed. Kaplan-Meier survival curves and a Cox model of survival were produced. Results: 1794 total patients were seen over the five year period. Cancer is the most common primary diagnosis (47%). Growth in annual PCC has risen dramatically (113 in 2003 vs. 414 in 2007) despite stable total hospital admissions. Patient are predominantly men (52% vs. 48%, p=0.02); median age is 76. General medicine, medical cardiology, and medical intensive care unit services refer most often. Most frequent issues addressed are goals of care, dismissal planning, and pain control (29%, 19%, 17%). PCC in actively dying pts have increased with 27% of all non-operating room, non-trauma in-hospital deaths being seen. Although CA pts have the highest median survival after PCC vs. other diagnoses (17 days, p = 0.018), we observed a five-year trend of decreasing survival from admission to death and PCC to death. Median time from admission to death in CA pts is 36 days in 2003 and 19 days in 2008 (p<0.01). Median time from PCC to death is 33 versus 11.5 days (p<0.01). Despite this, median hospital length of stay and time from PCC to discharge have remained fixed at 8 and 2.5 days, respectively. A Cox model of survival to discharge and <6 months survival (hospice eligibility) shows hospital length of stay, time from consult to discharge, and dismissal location from hospital are all prognostic factors. Conclusions: Survival window for PC intervention for CA pts is lessening. With the trend of shorter survival after PCC, PC professionals have little over two days to implement a comprehensive, ongoing care plan. This highlights the importance of earlier outpatient palliative care involvement with advanced cancer patients and families. No significant financial relationships to disclose.

10601 Background: Brachial plexopathy is a well-recognized complication of breast cancer, most attributed to late effects of radiation. However, direct involvement of brachial plexus by recurrent breast cancer occurs. Misdiagnoses may lead to inappropriate attribution of the plexopathy to radiation, and therefore inappropriate therapy. Methods: We report fourteen cases of brachial plexopathy secondary to breast cancer diagnosed at the Mayo Clinic-Rochester from 2003 to 2005. Results: Thirteen of fourteen primary tumors and 12/14 recurrences were ER/PR positive. Only 1/14 patient had Her 2 neu overexpression. The median time from the original breast cancer diagnosis to first brachial plexus symptom was 14 years. The median time from the development of symptoms to diagnosis was 8 months with the range being 1 month to 8 years. MRI revealed a distinct mass in 3/13 patients, plexus thickening in 5/13, and was normal in 5/13. Only 5/13 original MRI interpretations suggested tumor. In four patients that the 1.5 T MRI was either interpreted as normal or unlikely cancer the 3 Tesla MRI revealed abnormal uptake suggestive of malignancy. PET scan suggested malignancy in 3/6 patients. Two of these cases had other metastatic disease. In the other three cases that PET scans were done the uptake was mild, suggesting inflammation rather than malignancy. Reinterpretations of the PET scan and MRI in combination by an experienced musculoskeletal radiologist was highly suggestive of malignancy in all cases. Definitive diagnosis was eventually obtained by biopsy of the brachial plexus (7/14) or another site of metastasis in (4/14). Conclusions: The often slowly progressive nature of hormonally driven breast cancer can mimic radiation induced brachial plexopathy. In the cases reviewed, PET was not reliable in differentiating inflammation from tumor. MRI findings are nonspecific and higher resolution 3T MRI may be needed to detect an abnormality. Interpretation of MRI and PET together is useful. Patients with a history of breast cancer, and brachial plexus symptoms should be carefully evaluated with consideration for recurrent disease as a cause. Biopsy of the brachial plexus can be done safely and has an important role in diagnosis. No significant financial relationships to disclose.

Abstract Background Activating mutations in PIK3CA occur in approximately 40% ER+BC. MK-2206 (M), a pan-AKT inhibitor, induced apoptosis of ER+ BC under estrogen deprivation in preclinical studies. We conducted this neoadjuvant trial to determine the pathologic complete response (pCR) rate of M plus anastrozole (A) for PIK3CA mutant (Mut) ER+ BC. Methods This single arm open label study of M+A used a 2-stage Simon phase II design (stage 1, n=16; stage 2, n=13, alpha=0.10, power=0.90) to test whether pCR rate &lt;1% (based on historical data with A alone), against the alternative that pCR rate ≥15% in PIK3CA Mut ER+ BC. At least 1 pCR in stage 1 was required to proceed to stage 2. Eligible patients (pts) with clinical stage II or III ER+HER2- BC were pre-registered and proceeded to a research tumor biopsy for PIK3CA sequencing, followed by treatment with daily A monotherapy for 28 days (cycle 0). Pts with PIK3CA Mut BC were subsequently registered, underwent a second biopsy, and started M (150mg PO weekly) with daily A on cycle 1 day 1 (C1D1) for a maximum of four 28-day cycles followed by surgery. Goserelin was added for premenopausal pts. A tumor biopsy on C1D17, 17 days post the start of M, was performed. Those with C1D17 Ki67 &gt;10% discontinued study treatment. pCR was defined as no invasive cancer in the breast and the lymph nodes. Tumor specimens collected at all timepoints are being analyzed for markers of proliferation, apoptosis, and PI3K pathway activity, gene expression microarray, intrinsic subtypes, and next generation sequencing of 83 genes. Results Of the 51 pts pre-registered, 35 pts did not register due to no PIK3CA mutation (n=22), inadequate specimen for testing (n=6), physician/pt decision (n=7). The remaining 16 pts (median age: 58, range: 40-77 years) received combination therapy. Three pts did not complete 4 cycles due to C1D17 Ki67 &gt;10% (n=2) and intolerability (grade (Gr) 4 transaminase elevation in C1, n=1). Other severe toxicities possibly related to M included Gr 3 rash (25%) and pruritus (12.5%). Of the 13 pts completed study therapy and underwent surgery, all had residual disease in the breast and 7 also had positive nodes. Table 1 summarized changes in Ki67 during treatment. ComparisonsnAbsolute changes in Ki67 median (range)Wilcoxon signed rank p-valueC1D1 relative to pre-registration11-17.0% (-49.8 to 4.1%)0.0020C1D17 relative to pre-registration14-16.4% (-51.4 to 4.1%)0.0004C1D17 relative to C1D112-1.5% (-18.6 to 15.8%)0.9697C1D1, biopsy post 28 days of A alone; C1D17 biopsy post 17 days on combination therapy Although Ki67 levels post A monotherapy (C1D1) or M+A (C1D17) were significantly lower than that of pre-registration samples, Ki67 did not differ between C1D17 and C1D1 samples. Other correlative studies are ongoing and results will be presented. Conclusion Despite the small sample size, biomarker analysis on serial biopsy specimens demonstrated that M+A is unlikely to be more effective than A alone in PIK3CA Mut ER+ BC. This trial demonstrated the feasibility of genomic sequencing for pt selection and the value of a small, well-designed proof-of-principle neoadjuvant trial for the evaluation of targeted agents. Citation Format: Ma CX, Suman VJ, Goetz M, Northfelt D, Burkard M, Ademuyiwa F, Naughton M, Margenthaler J, Aft R, Gray R, Tavaarwerk A, Wilke L, Haddad T, Moynihan T, Loprinzi C, Hieken T, Hoog J, Guo Z, Han J, Vij K, Mardis E, Sanati S, Al-Kateb H, Doyle L, Erlichman C, Ellis MJ. A phase II neoadjuvant trial of MK-2206, an AKT inhibitor, in combination with anastrozole for clinical stage 2 or 3 PIK3CA mutant estrogen receptor positive HER2 negative (ER+HER2-) breast cancer (BC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-04.

Abstract Background: The potential for exploiting BRCA deficiencies with DNA repair inhibitors has both pre-clinical and clinical support. ABT-888 (veliparib), a DNA repair inhibitor initially thought to target Poly(ADP-Ribose) Polymerases (PARP), has demonstrated in vitro inhibition of BRCA1 and BRCA2 deficient mouse embryonic stell cells, with a larger effect on BRCA1 cells. We report on the pre-planned interim analysis of the efficacy of single agent veliparib in patients with either BRCA1 or BRCA2-associated stage IV breast cancer. Methods: BRCA 1 or 2 carrier patients with stage IV breast cancer, with measurable disease, without prior exposure to a PARP inhibitor or a platinum compound in the metastatic setting, were eligible. Velapirib was administered orally, at doses of 400 mg twice daily. Dose adjustments based on toxicity were permitted. Patients progressing on velapirib alone received carboplatin at an AUC of 5, IV, given Q 21 days, and velapirib 150 mg twice daily (the maximum tolerated dose [MTD] of the combination from our completed Phase I study: J Clin Oncol 30, 2012 [suppl; abstr 1024]). Patients were to be accrued from 7 NCI NO1- supported consortia. Initially 10 patients were to be accrued to each stratum (BRCA1 and BRCA2) to provide evidence of single agent activity. If there was sufficient activity to warrant consideration of velapirib as single agent therapy (defined as 2 or more confirmed partial [PR] or better responses out of 10 per stratum), an additional 12 patients would be accrued per stratum. Results: 20 evaluable patients (11 BRCA1 and 9 BRCA2 [1 in screening]) have been accrued, the majority with lung or liver as visceral metastatic sites of disease. Median age (range) is 46 (29-68) years. Tumors from 9 patients were hormone receptor positive. BRCA1 cohort: 4 of 11 patients are off treatment at a median of 2 months (1-4); 1 patient stopped velapirib due to toxicity (grade 2 rash/pruritus, grade 2 vomiting), 3 stopped for progressive disease (one with an unconfirmed PR). Seven patients are still on single agent veliparib with 1 unconfirmed PR, and 1 patient with two evaluations showing stable disease. BRCA2 cohort: 2 patients are off treatment at 2 months for progressive disease, 7 are still on treatment with 1 confirmed PR, and 3 unconfirmed PRs. Data on patients receiving combination of velapirib and carboplatin after progression is too early. Treatment-related toxicity is being updated and has so far been reported from 14 patients: 1 patient had grade 3 fatigue, 1 patient with liver metastasis had both grade 3 alanine aminotransferase elevation and grade 3 abdominal pain. Grade 2 toxicities occurring in more than 1 patient included nausea/vomiting (6 patients), chills (2 patients), and fatigue (2 patients). Conclusion: Velapirib has single agent activity in both BRCA1 and BRCA2-associated stage IV breast cancer patients, and is well-tolerated. Mature response, treatment, and toxicity data will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-05.