Jessica A. Zerillo

Pulse Afatinib for ERBB2 Exon 20 Insertion-Mutated Lung Adenocarcinomas.

Introduction: Genomic aberrations involving the erb‐b2 receptor tyrosine kinase 2 gene (ERBB2) are driver oncogenes in approximately 2% of lung adenocarcinomas. However, the use of daily dosing of ERBB2 tyrosine kinase inhibitors (TKIs)—including afatinib—has been fraught with plasma concentrations that barely achieve preclinical model inhibition, significant patient‐reported toxicities, and limited clinical activity. We hypothesized that alternative dosing strategies could improve tolerability and efficacy. Methods: We profiled lung cancer cell lines against TKIs and retrospectively evaluated the toxicity of and response to pulse afatinib (280 mg once weekly) in lung cancers with ERBB2 mutations. Results: An ERBB2 exon 20 insertion–mutated lung cancer cell line had a 50% inhibitory concentration in response to afatinib that was higher than the reported plasma concentration of afatinib, 40 mg daily. Three patients with advanced ERBB2‐mutated lung adenocarcinomas were treated with off‐label pulse afatinib. The 280‐mg weekly dose was well tolerated with no reported rash and minimal diarrhea. One TKI‐naive patient achieved a partial response for 5 months and another achieved stable disease for 11 months. Conclusions: Pulse afatinib at a weekly dosing scheme induced antitumor activity in ERBB2 exon 20 insertion–mutated lung adenocarcinomas. Future clinical trials of alternative dosing schemes of ERBB TKIs as monotherapy or in combination with other therapies are warranted for ERBB2‐mutated tumors.

An International Collaborative Standardizing a Comprehensive Patient-Centered Outcomes Measurement Set for Colorectal Cancer

Importance Global health systems are shifting toward value-based care in an effort to drive better outcomes in the setting of rising health care costs. This shift requires a common definition of value, starting with the outcomes that matter most to patients. Objective The International Consortium for Health Outcomes Measurement (ICHOM), a nonprofit initiative, was formed to define standard sets of outcomes by medical condition. In this article, we report the efforts of ICHOM’s working group in colorectal cancer. Evidence Review The working group was composed of multidisciplinary oncology specialists in medicine, surgery, radiation therapy, palliative care, nursing, and pathology, along with patient representatives. Through a modified Delphi process during 8 months (July 8, 2015 to February 29, 2016), ICHOM led the working group to a consensus on a final recommended standard set. The process was supported by a systematic PubMed literature review (1042 randomized clinical trials and guidelines from June 3, 2005, to June 3, 2015), a patient focus group (11 patients with early and metastatic colorectal cancer convened during a teleconference in August 2015), and a patient validation survey (among 276 patients with and survivors of colorectal cancer between October 15, 2015, and November 4, 2015). Findings After consolidating findings of the literature review and focus group meeting, a list of 40 outcomes was presented to the WG and underwent voting. The final recommendation includes outcomes in the following categories: survival and disease control, disutility of care, degree of health, and quality of death. Selected case-mix factors were recommended to be collected at baseline to facilitate comparison of results across treatments and health care professionals. Conclusions A standardized set of patient-centered outcome measures to inform value-based health care in colorectal cancer was developed. Pilot efforts are under way to measure the standard set among members of the working group.

Administration of Oral Chemotherapy: Results From Three Rounds of the Quality Oncology Practice Initiative

PURPOSE Although use of oral chemotherapy is becoming more prevalent, little is known about the quality of care that patients receive when these agents are prescribed. Moreover, few practice-level systems are in place to ensure safe management of oral chemotherapy in the vulnerable population of patients with cancer. METHODS We analyzed results from 155 practices that were voluntarily participating in the American Society of Clinical Oncology Quality Oncology Practice Initiative (QOPI) program on 17 test measures of oral chemotherapy administration and management in at least one of three collection periods: spring or fall of 2012, or spring of 2013. The 17 test measures cover three domains: treatment plan documentation, patient education, and adherence/toxicity monitoring. We defined composite scores for each of the three domains. We analyzed the composite scores by secular trend and tested the difference in composite scores for the three domains. Additionally, we tested change in scores over time among practices that participated at least twice. RESULTS The majority of data was provided by QOPI-certified practices. Overall, mean practice composite scores ranged from 66% to 68% for treatment plan documentation, 51% to 57% for patient education, and 75% to 81% for adherence/toxicity monitoring. Composite scores for practices that participated more than once did not improve significantly. CONCLUSION The collection of oral chemotherapy test measure data is feasible. Composite scores for treatment plan documentation and patient education were not only lower, but had greater variability compared with adherence/toxicity monitoring. Improvement opportunities exist for patients who are prescribed oral chemotherapy.

Interventions to Improve Oral Chemotherapy Safety and Quality: A Systematic Review

Importance With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective systems to administer and manage these agents. A comprehensive synthesis of literature on oral chemotherapy care delivery programs to which clinicians can look for best practices is lacking. Objective To summarize the peer-reviewed and gray literature on interventions to improve oral chemotherapy care delivery toward describing best practices and identifying current gaps. Evidence Review Using search terms pertaining to the concepts of oral chemotherapy, cancer, and interventions and outcomes, we performed a systematic review of PubMed, EMBASE, and CINAHL from January 1995 to May 24, 2016, to identify oral chemotherapy intervention programs. We searched the gray literature from January 1995 through February 2016 and contacted gray literature authors for further information. Four physician abstractors reviewed the titles, abstracts, and articles. Quality of the articles was assessed using SQUIRE2 guidelines. Interventions were evaluated in the categories of prescribing, preparation/dispensing, education, administration, monitoring, and storage/disposal. The population of interest included all ages and was limited to traditional cytotoxic and targeted anticancer oral agents. Findings From 7984 abstracts identified in the peer-reviewed literature search, 16 full-text articles met inclusion criteria representing 3612 patients. Interventions focused on prescribing (n = 1), preparation/dispensing (n = 2), education (n = 11), administration (n = 5), monitoring (n = 14), and storage/disposal (n = 1). In the 10 articles with adherence as the primary outcome, 4 evaluation methods were used. Most improvements were seen in toxic effects/safety compared with adherence. Of the 7 interventions with statistically significant improvement in the primary outcome, 3 nursing phone calls to contact patients within the first few days after treatment initiation, 2 of them with standardized toxic effects management protocols. Interventions using technology to increase touch points between care teams and patients (including video directly observed therapy, automated voice response, and text messages) were not effective. Conclusions and Relevance A framework for the oral chemotherapy management process with standardized outcome definitions is needed to ensure constructive research. Existing data suggest that a monitoring program should include personal contact with patients within the first weeks of treatment. Whether such contact can be enhanced by technology is uncertain.

Morbidity and Mortality Revisited: Applying a New Quality Improvement Paradigm in Oncology

Using a quality improvement (QI) paradigm, the authors conducted 11 multidisciplinary conferences throughout 2013-2014 at two tertiary academic cancer centers and a satellite community-based oncology practice. They present their approach including key components and an example case.

Understanding Oral Chemotherapy Prescribing Patterns at the End of Life at a Comprehensive Cancer Center: Analysis of a Massachusetts Payer Claims Database.

PURPOSE Receipt of chemotherapy in the last 14 days of life is a measure of potential overuse of care. Specific measures defining appropriate end-of-life use of oral agents have not yet been described, and little is known about prescribing patterns. METHODS We conducted an exploratory analysis of 371 patients at Dana-Farber Cancer Institute who were covered by the Blue Cross Blue Shield of Massachusetts pharmacy benefit and died during 2012 to 2013. We analyzed processed claims as a surrogate for chemotherapy administration. We compared oral with parenteral chemotherapy claims in the last 6 months of life. RESULTS In the last 6 months of life, 294 patients (79%) had chemotherapy claims, including 81 (22%) prescribed an oral agent; 20 patients had claims for oral chemotherapy in the last 30 days of life. For eight patients (40%), this was the initial start of that oral agent. In the last 14 days of life, only 23 patients had chemotherapy claims, including six patients prescribed an oral agent. CONCLUSION The collection of oral chemotherapy use data through insurance claims was feasible. Processed claims for chemotherapy, including oral, sharply declined during the last 30 days of life, consistent with a shift to palliative management. These results highlight the need for a more comprehensive analysis of oral chemotherapy prescribing patterns and development of specific measures to define the appropriate use of oral chemotherapy at the end of life.

Developing a model for embedded palliative care in a cancer clinic

Objectives Describe the development and key features of a model for embedded palliative care (PC) for patients with advanced kidney cancer or melanoma seen in a cancer clinic. Methods Retrospective chart review of patients following an initial phase and then a prospective review following the implementation of a model for embedded PC. Results In the initial phase, 18 patients were seen for a total of 53 visits; 78% were seen more than once, with a mean of three visits per patient. In the model phase, 46 patients were seen for a total of 163 visits; 74% were seen more than once, with a mean of 3.5 visits. Demographics were similar between the two groups. Content of the first PC visit in the initial and model phases was symptom management (61% and 57%), psychosocial support/relationship building (28% and 35%) and advance care planning/decision-making support (11% and 8%), respectively. Conclusions The initial phase demonstrated acceptability and feasibility of a model for embedded PC for patients and the oncology team. Establishment of specific eligibility criteria and screening to identify eligible patients in the model phase led to an increased uptake of PC for patients with advanced kidney cancer and melanoma in a cancer clinic.

Home Medication Safety and Adherence

There has been a shift from inpatient to ambulatory care, including home care, for many reasons, including the growing emphasis on providing patient-centered care. For pediatric hematology/oncology patients, this shift has included the administration of oral and parenteral chemotherapy, clotting factors, as well as oral and parenteral antibiotics and nutrition. Along with the other home medications for pediatric hematology/oncology, such as oral immunosuppressants, over-the-counter and prescription medications to treat symptoms, including narcotics, and herbal medications, these home medications now have to be managed and administered by parents/caregivers and adolescents. This change away from the inpatient or clinic-based pharmacy as the dispensary and the nurse as the administrator results in a loss of our traditional safety nets and opens new vulnerabilities for errors and nonadherence.

Clinical trial enrollment expansion to the community.

112 Background: Oncology patients at community cancer practices generally do not access clinical trials to the same degree as patients at academic medical centers. Collaborations between research and clinical teams across academic hospitals and their affiliated community sites may help to improve this disparity. METHODS To improve clinical trial enrollment, a multidisciplinary team of research and clinical staff from the Dana-Farber Cancer Institute main campus and a community-based satellite site implemented a program to enhance identification of breast cancer patients eligible for clinical trials. The team constructed a process map, cause and effect diagram and collected diagnostic data, which was displayed with a Pareto chart. Process control charts were used to track data over time. Interventions included: (1) a web-based tool to pre-screen patients for community and main campus trials, (2) a training session for clinicians on trial communication skills, (3) designated clinician visits for follow-up trial discussions, and (4) research nurse telephone calls after the initial consultation. RESULTS Before the program (7/14-10/14), research staff screened 83% of new breast cancer patients for clinical trials, which increased to 97% after the program (11/14-9/15) (p < 0.001). There was not a significant change in trials presented to eligible patients or enrollment in trials. CONCLUSIONS The proportion of patients identified for clinical trials increased and there was numeric improvement in the proportion of eligible patients presented trials. There was an increase in clinical trial enrollment that did not reach statistical significance, possibly due to the low sample size. These results suggest that the interventions would benefit from further modification and use. The project demonstrates the challenges and opportunities inherent in growing successful clinical trial programs in community-based satellite sites. [Table: see text].

Impact of integrated palliative care model on end-of-life (EOL) quality metrics for patients with kidney cancer (RCC) and melanoma (M).

137 Background: Early palliative care (PC) improves quality of life (QOL) and enhances end-of-life (EOL) care, but the optimal timing and most effective model for integrating PC into oncologic care is uncertain. To understand the impact of an integrated model with PC providers embedded with oncologists vs. usual care (UC) with referral at the discretion of the same oncologists, we examined the timing and delivery of PC and Quality Oncology Practice Initiative (QPOI) EOL metrics among patients with RCC and M in a single clinic. We hypothesized that integrated PC would result in more referrals, earlier contact with PC and better QOPI EOL metrics compared with UC. METHODS In a retrospective cohort study of patients with RCC and M in the Beth Israel Deaconess Biologics Clinic who expired between 10/1/12 and 12/31/14, we compared patients seen 2 days/week, when referral to PC was discretionary, with a third day when PC providers shared the clinic for real-time consultations. Patients were identified as meeting PC eligibility if they had recurrent, metastatic disease and were on active treatment or had a symptom severity of 7+ on Edmonton Symptom Assessment Scale (ESAS). Two oncologists saw all patients, regardless of day. RESULTS Seventy-six patients expired, 19 in the Integrated PC model and 57 with UC. Patients were similar with respect to diagnosis and demographics except for smoking. The integrated model substantially improved timing and location of PC. In the integrated PC model, 85% were seen by PC compared with 45% in UC (P = 0.002). All patients in the integrated model began PC as an outpatient compared with 36% in UC (P < 0.001). The mean number of days from first PC contact to death was 28 (SD = 54) for UC and 118 (SD = 120) with integrated PC (P < 0.001). The location of death did not differ significantly between models, occurring outside the hospital with hospice among 71% of patients in the integrated model and 53% in UC (P = 0.25). Results were similar in relative risk models adjusted for smoking. CONCLUSIONS A practice model that integrated PC with oncologic care was associated with more PC referrals, earlier contact, and a nonsignificant trend toward fewer deaths in hospital and ICU.