Implementation of the Quality Oncology Practice Initiative Program in Spain: First Results and Implications

PURPOSE: Measuring and tracking quality of care is highly relevant in today's health care. The Quality Oncology Practice Initiative (QOPI) program is a referral for evaluating oncology practices worldwide. Excellence and Quality in Oncology Foundation, a collaboration of oncology experts from major Spanish hospitals involved in cancer treatment, reached an agreement with QOPI to include Spanish hospitals in this program. METHODS: We analyzed the results of the QOPI Core module measures from 19 Spanish hospitals over nine rounds (from fall 2015 to fall 2019). RESULTS: Of the 19 hospitals, 15 completed more than one round; none participated in all nine (two hospitals participated in eight rounds). The highest scores were for pathology report confirming malignancy, documenting a plan of care for moderate or severe pain and chemotherapy dose, and chemotherapy administered to patients with metastatic solid tumor with performance status undocumented. Measures regarding a summary of chemotherapy treatment, tobacco use cessation counseling, and assessment of patient emotional well-being were among the lowest scored measures. Six of the 15 practices that participated repeatedly achieved a better score in their last round compared with their first. Overall, scores of Spanish hospitals improved from 67.79% in fall 2015 to 68.91% in fall 2019. CONCLUSION: To our knowledge, this is the first study to evaluate QOPI scores in Spain. There was high variability in scores, with quality of care improving with repeated participation in some hospitals, but worsening in others. Excellence and Quality in Oncology Foundation will support practices to increase their participation to improve oncology care and implement strategies that address the areas for improvement.

Platform trial of BI 754091, an anti-PD-1 antibody, in patients with previously treated advanced solid tumors: Combination with BI 836880, a VEGF/Ang2-blocking nanobody.

TPS152 Background: Combining anti-programmed cell death protein 1 (PD-1) antibodies with other immuno-modulatory or targeted therapies may improve outcomes. NCT03697304 is an open-label, Phase II, platform trial assessing BI 754091, an anti-PD-1 antibody, combined with other agents. Here, we describe Module C in which BI 754091 will be combined with BI 836880, a humanized bispecific nanobody, that targets vascular endothelial growth factor (VEGF) and angiopoietin2 (Ang2). VEGF and Ang2 play key roles in tumor angiogenesis and have an immunosuppressive effect in the tumor microenvironment. Combining anti-VEGF/Ang2 with an anti-PD-1 therapy promotes an immunopermissive state supportive of T-cell-mediated tumor cell death. Methods: Patients are being enrolled in 5 cohorts: 1) locally advanced/metastatic gastric or gastroesophageal adenocarcinoma with ≥1 prior treatment (anti-PD-[L]1 naïve); 2) any advanced/metastatic solid tumor (excluding NSCLC and melanoma) with prior anti-PD-(L)1 treatment, which progressed after achieving at least stable disease (SD) for 4 months; 3) advanced/metastatic solid tumors with no benefit from prior anti-PD-(L)1 treatment (SD <4 months); 4) locally advanced/metastatic microsatellite stable (MSS) colorectal cancer with ≥1 prior treatment (anti-PD-[L]1 naïve); 5) advanced MSS and mismatch-repair proficient endometrial carcinoma which progressed following 1 line of chemotherapy (anti-PD-[L]1 naïve). Patients will receive BI 836880 (720 mg every 3 weeks [Q3W] intravenously [IV]) and BI 754091 (240 mg Q3W IV). Treatment will continue until progressive disease, unacceptable toxicity, consent withdrawal, or for a maximum of 1 year (treatment may be extended in case of clinical benefit). The primary endpoint is objective response (OR; complete or partial response per RECIST v1.1 as assessed by the investigator). Secondary endpoints are duration of OR, disease control and progression-free survival. Safety will also be assessed. Approximately 30 patients will be enrolled per cohort at sites in North America and the United Kingdom. Clinical trial information: NCT03697304.

Identifying high-risk features for readmission in patient with metastatic solid tumor malignancies at an academic community hospital.

217 Background: Readmission of oncology patients to hospitals is an undesirable outcome for both the patient and healthcare system. These can lead to delays in treatment and increased resource utilization. 30-day readmission have been a target of multiple national quality initiatives. Adverse outcomes have been associated with readmission in multiple patient populations. The aim of this study was to perform a qualitative and quantitative analysis on inpatient solid tumor medical oncology readmissions to an academic community hospital. Additionally, identifying additional risk factors for readmission such as need for fluid drainage and rate of palliative care involvement were assessed. Methods: Using ICD-10 codes, 183 patients were identified as being readmitted within 30 days with a known oncological diagnosis from January 2019-Decemember 2019. Only the most recent readmission was included for review. 54 of these patients were selected at random for manual chart review to generate data. Results: In the 54 patients who underwent detailed review, 21 were identified as having stage IV metastatic sold tumor disease primarily under the care of a medical oncology team. Common factors identified for readmission included malignant abdominal ascites (6 patients), thoracic pleural effusions requiring drainage (5 patients), CNS/spinal metastases (4 patients). Palliative care was consulted in the index admission in 48% of cases analyzed. In patients with metastatic solid tumor disease, 17/21 (81%) of patients were discharged on a weekday. Examples of preventable readmissions identified included inadequately treated hypercalcemia of malignancy and cerebral edema due to brain metastases discharged with insufficient corticosteroid dosing. Conclusions: The high-risk features identified (e.g. recurrent malignant ascites) may benefit from novel systems-based approaches (i.e. EMR alerts, daily oncology/palliative care team huddle to discuss high risk patients). Most patients readmitted to the oncology service with metastatic disease were not discharged on a weekend day. This analysis also revealed under-utilization of palliative care during the index admissions for these oncology patients with known metastatic disease. Further quality initiatives will be directed at creation of a risk score for readmission in this subset of patients with high disease burden.

Sunitinib facilitates metastatic breast cancer spreading by inducing endothelial cell senescence

Background Sunitinib, a receptor tyrosine kinase (RTK) inhibitor that targets multiple receptors such as vascular endothelial growth factor receptors (VEGFRs), was approved for cancer treatment in 2006. However, it was unsuccessful in treating certain cancers, particularly metastatic breast cancer (MBC), and the mechanism underlying this “sunitinib resistance” remains unclear. Herein, we investigated whether the sunitinib-associated inferior survival benefit in MBC was due to sunitinib-induced endothelial cell (EC) injury or EC senescence. Methods 4T1 murine breast cancer cells were used as the main breast tumor model for it produces a highly metastatic solid tumor that can spontaneously metastasize to the lung, which closely mimics highly metastatic human breast cancer. Senescence-associated β-galactosidase (SA-β-Gal, immunohistochemistry [IHC]-staining), P16, P53, and P57 (immunoblotting) were used as markers of cell senescence. A protein array containing 25 senescence-associated chemokines and the transwell chemotaxis assay were used to examine whether sunitinib increases inflammatory chemokine secretion which attracts tumor cells via chemokinesis. Flow cytometry and IHC were used to detect whether the sunitinib-induced senescent ECs recruit cancer-associated inflammatory myeloid cells. Finally, the spontaneous metastatic model was used to monitor whether sunitinib causes the formation of “pre-metastatic niche” which promotes MBC to metastasize to the lungs. Results We demonstrated that sunitinib induced a senescence-like endothelial cell (EC) phenotype. Inflammatory chemokine secretion and VCAM1 expression were significantly increased in senescent ECs, resulting in tumor cell (TC) chemotaxis and TC/EC interactions. Meanwhile, EC senescence caused loosening of EC junctions, facilitating TC transmigration through the endothelial barrier. Sunitinib-induced senescent ECs also recruited cancer-associated myeloid cells to form a “pre-metastatic niche”-like microenvironment. Alterations at the molecular level and in the tissue environment ultimately led to an increase in distant metastasis. Conclusion Although sunitinib was designed to target the EC directly, the increase in tumor metastasis may ironically be due to sunitinib “correctly” playing its role. Our findings suggest that we should carefully weigh the pros and cons before using sunitinib and other antiangiogenic drugs that directly target the ECs.

Total Number of Alterations in Liquid Biopsies Is an Independent Predictor of Survival in Patients With Advanced Cancers

PURPOSE Studies have demonstrated an association between quantity of circulating tumor DNA (ctDNA) and poorer survival. We investigated the relationship between percent ctDNA (%ctDNA), total number of ctDNA alterations, and overall survival (OS) in liquid biopsies. MATERIALS AND METHODS Overall, 418 patients with blood-based next-generation sequencing (54 to 73 genes) were analyzed. Eligible patients included those who had advanced/metastatic solid tumor malignancies and never received immunotherapy treatment, which may alter the survival curve in patients with high mutational burden. RESULTS Patients with a high (≥ 5%) %ctDNA had significantly shorter OS versus those with intermediate (≥ 0.4% to < 5%) or low (< 0.4%) values (median OS, 7.0 v 14.1 v not reached [NR] months, respectively; P < .0001). Patients with a high (≥ 5) total number of alterations had significantly shorter OS versus those with intermediate (≥ 1.46 to < 5), low (< 1.46), or no alterations (median OS, 4.6 v 11.7 v 21.3 v NR months, respectively; P < .0001). The total number of alterations correlated with %ctDNA (r = 0.85; 95% CI, 0.81 to 0.87; P < .0001). However, only an intermediate to high total number of alterations (≥ 1.46) was an independent predictor of worse OS (hazard ratio, 1.96; 95% CI, 1.30 to 2.96; P = .0014; multivariate analysis). CONCLUSION We demonstrate that the total number of alterations and %ctDNA have prognostic value and correlate with one another, but only the total number of alterations was independently associated with survival outcomes. Our findings suggest that the total number of alterations in plasma may be an indicator of more aggressive tumor biology and therefore poorer survival.

Camrelizumab in advanced or metastatic solid tumor patients with microsatellite instability–high/mismatch repair-deficient: Results from an open-label exploratory study.

e15140 Background: PD-1 checkpoint inhibitor has been shown a significant effect in patients (pts) with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumor. Herein, we assessed the efficacy and safety of camrelizumab, a PD-1 checkpoint inhibitor, in advanced or metastatic solid tumor pts with MSI-H/dMMR. Methods: Pts with MSI-H/dMMR solid tumor who had received at least one line of prior systemic chemotherapy were recruited in this single-arm exploratory study. Pts received camrelizumab (200mg, ivd, D1/2W) until disease progression or intolerable toxicity. Response was assessed every 8 weeks. The primary endpoint was objective response rate (ORR) according to RECIST v1.1 criteria. This study was registered at Chinese Clinical Trial Registry, ChiCTR-OIC-17013249. Results: From November 2017 to February 27, 2019, 12 eligible pts were recruited, which covered 9 cancer types. The median age was 58 (range 27-72) years; male/female was 58.3/41.7%. 11 pts were confirmed as MSI-H status, and 1 patient as d-MMR status. All pts were included in efficacy and safety analysis. 2 pts achieved complete response (CR), 6 pts partial response (PR), 4 pts stable disease (SD), yielding the ORR of 66.7% (95% CI: 34.9-90.1), and the disease control rate of 100% (95% CI 73.5-100) at best. What’s more, cancer types of CR pts covered rectal cancer and bladder cancer (1 patient each); PR pts included colon cancer, liver cancer, endometrial cancer, ureteric cancer, intrahepatic cholangiocarcinoma, and small intestine cancer (1 patient each); SD pts contained 3 colon cancer pts and 1 retroperitoneal leiomyosarcoma patient. The overall incidence of adverse incidences (AEs) was 100%. The incidence of Grade ≥3 AEs was 58.3%, which mainly included anemia (16.7%), increased γ-transglutaminase (16.7%), increased alkaline phosphatase (16.7%), increased blood bilirubin (16.7%). As of Oct 30, 2019, 11 pts were still on study medication. Conclusions: Camrelizumab resulted in encouraging objective response and tolerable toxicity in MSI-H/dMMR advanced or metastatic solid tumor. The survival benefits will be further observed. Clinical trial information: ChiCTR-OIC-17013249 .

Outcomes for patients with metastatic solid malignancies who achieve a complete response on an immune checkpoint inhibitor.

82 Background: Use of immune checkpoint inhibitors (ICI) in metastatic solid malignancies can occasionally result in a complete response (CR). There is limited long-term data regarding outcomes for patients who achieve a CR on ICIs. Methods: We screened the Mayo Clinic electronic medical record using an institutional database query program to identify patients whose records contained keywords such as “pembrolizumab” and “complete response” or “no evidence of disease.” Patients were included if they had measurable metastatic solid tumor disease prior to initiation of ICI and if they had a CR defined by two consecutive imaging studies at least twelve weeks apart. Exclusion criteria included oligometastatic disease treated with locoregional therapy or presence of a second confounding malignancy. Results: One-hundred four patients with a CR on pembrolizumab met criteria. Most (71.1%) patients had melanoma and 63/103 (61.2%) received had received the ICI during the first line of metastatic systemic therapy. Additional characteristics are in Table. At a median follow-up of 35.8 months (6.1-87.7), patients had received ICI for a median of 12.1 months (1.5-46.7). The vast majority of patients who stopped ICI did so electively (for reasons other than disease progression). Of 88 elective discontinuations, only 7 patients had disease recurrence after a median follow-up from start of ICI of 40.5 months. Conclusions: Patients with a metastatic solid malignancy who achieve a CR to pembrolizumab appear to maintain remissions off therapy, with low rates of relapse. Further outcomes will be explored, including analyzing and characterizing a sub-group of “hyper-responders” and patients receiving other ICI agents. [Table: see text]

DEVELOPING AND IMPLEMENTING ALIVIADO DEMENTIA CARE IN HOSPICES: CHALLENGES ENCOUNTERED AND LESSONS LEARNED

Hospice was originally developed to care for individuals with metastatic, solid-tumor cancers. While advanced ADRD is now the primary illness in approximately 19% of the hospice population and presents as a co-morbid condition in many more, little evidence-based work has been performed to retool hospice to care for persons with ADRD and their caregivers. Aliviado Dementia Care-Hospice Edition is a systems level change program consisting of hospice workforce training, an implementation toolbox, and agency-wide workflow changes. Aliviado seeks to improve the quality of life for persons with ADRD and their caregivers receiving hospice, focused specifically on BPSD and pain assessment and management. In developing a coalition of hospice agencies and implementing this pragmatic intervention, we discuss our solutions to overcoming a number of barriers, including varying electronic health records, performing culture change with a disseminated workforce, scaling to 25 hospices, and working with some hospices who lack experience performing research.