HOPA Members Present Research at the 2017 American Society of Clinical Oncology Annual Meeting
Alissa Karr, PharmD BCOP
Oncology Clinical Pharmacist
Markey Cancer Center
University of Kentucky HealthCare
HOPA members had the opportunity to highlight their research during poster sessions at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, June 2–6. Featured in this article are excerpts from research and e-published abstracts from HOPA members who were the primary author. Additional members, listed at the end of the article, were secondary authors on posters and e-published abstracts. This article does not provide a comprehensive list; the authors had to self-report their presentations.
Abstract types: late-breaking abstract (LBA), trials in progress abstract (TPS), abstracts selected for publication but not for presentation at the annual meeting (e).
Dr. Edward Li and colleagues presented “Spending on Antineoplastic Agents in the United States: 2011–2016” (J Clin Oncol. 35, 2017 [suppl; abstr 6618]). Little information on trends in actual antineoplastic expenditure since the introduction of costly novel antineoplastic therapies is available. The objective of Dr. Li’s study was to describe antineoplastic expenditures by year and healthcare sector in the United States. Quintiles IMS National Sales Perspective data for the years 2011–2016 were evaluated to describe antineoplastic agent expenditures. After they were grouped by healthcare sector and calendar year, actual expenditures were adjusted for U.S. medical-cost inflation to 2016 dollars. Growth was calculated as the percentage increase from previous years. Results of the study showed a total increase in antineoplastic expenditures from $26.8 billion in 2011 to $38.9 billion in 2016. Rituximab, bevacizumab, nivolumab, trastuzumab, and pertuzumab accounted for the top five antineoplastic expenditures in the study period, with $3.7 billion, $3 billion, $2.6 billion, $2.6 billion, and $0.9 billion expenditures in 2016, respectively. Hospitals and clinics showed an increase in spending on biologics by 80% from 2011 to 2016. Cytotoxic drug spending remained flat during the time studied because of the availability of multiple generic products. Dr. Li and colleagues concluded that antineoplastic expenditures increased significantly from 2011 to 2016. Expenditures are expected to continue rising with the anticipated approval of additional costly novel antineoplastic agents and an aging population.
Drs. Michael Kane, Paul Auriemma, and colleagues presented “Financial Impact of Flat Dosed (FD) Monoclonal Antibodies (MABs) at a Single Institution in 2016” (J Clin Oncol. 35, 2017 [suppl; abstract 6617]). Immuno-oncology agents are important breakthrough treatments in cancer. Some agents were adjusted after initial Food and Drug Administration (FDA) approval to flat dosing instead of weight-based dosing. Flat dosing (FD) may be thought to simplify prescribing, dispensing, inventory, and billing. Nivolumab and pembrolizumab are FDA approved for several malignancies. Original studies established weight-based dosing of nivolumab 3 mg/kg every 2 weeks and pembrolizumab 2 mg/kg every 3 weeks. The FDA approved FD of nivolumab 240 mg in melanoma, renal cell carcinoma, and non–small cell lung cancer. The FDA approved FD of pembrolizumab 200 mg in melanoma and non–small cell lung cancer as well as other indications. Dr. Kane and colleagues looked at the financial impact of this FD methodology compared to weight-based dosing of nivolumab (3 mg/kg, capped at 240 mg), as well as weight-based dosing of pembrolizumab (2 mg/kg, capped at 200 mg). Availability of pembrolizumab in 50-mg vials was also assessed. The electronic medical record was used for applicable dispensed dose and patient’s weight. Wholesale acquisition costs (WAC) at the end of the year were used for financial comparison (Table 1 – see PDF).
In conclusion, weight-based dosing with a cap (nivolumab, 240 mg, pembrolizumab 200 mg) versus flat dosing would have saved $198,567 and $80,037, respectively. In addition, Dr. Kane and colleagues found savings of $760,351 if pembrolizumab in 50-mg vials was available. Wide-scale adoption of flat dosing for immune-oncology monoclonal antibodies may result in higher drug costs. FDA labeling to include weight-based and flat-dose options as well as appropriate multidose vial sizes would restrain the costs of care.
Drs. Samantha Reiss, Prakirthi Yerram, Lisa Modelevsky, and colleagues presented “Retrospective Review of Safety and Efficacy of Checkpoint Inhibition in Refractory High-Grade Gliomas” (J Clin Oncol 35, 2017 [suppl; abstr 2033]). Limited treatment options are available for refractory high-grade gliomas (HGGs). Programmed cell death ligand-1 (PD-L1) expression has been reported in 0%–61% of HGGs and therefore may be a suitable target. The study objective was to describe the safety and efficacy of PD-1 inhibition in patients with refractory HGGs. This was a retrospective single-center study. Adult patients who had pathologically confirmed HGG who had received a PD-1 inhibitor between September 2014 and October 2016 outside a clinical trial were included. Twenty-five patients were identified who had received pembrolizumab as compassionate use. The median age was 49 years, 44% were men, 52% had glioblastoma, and the median baseline Karnofsky Performance Status was 80 (range 50–100). Patients had received a median of four prior lines of therapy, with 19 (76%) having failed therapy with bevacizumab. Concurrent treatment included bevacizumab in 17 patients (68%) or bevacizumab and temozolomide in 2 patients (18%). The median number of doses was 3 (range 1–14). Treatment toxicity and response were assessed in 24 patients. Pembrolizumab-related adverse events (AEs) included liver function test elevations (33%), hypothyroidism (17%), diarrhea, (17%), myalgias and arthralgias (13%), and rash (8%). Other common AEs were hyperglycemia, fatigue, thrombocytopenia, lymphopenia, headache, and nausea in the setting of concomitant therapy and additional supportive care (dexamethasone). Grade 3 AEs included seizure (4%), headache (4%), nausea (4%), and vomiting (4%). Response rates were partial response (n = 2), stable disease (n = 50), and progressive disease (n = 17). Median progression-free survival (PFS) was 42 days (range 7–282), and median overall survival was 121 days (range 15–415). Three patients (12%) had a PFS >90 days; of these, two received single-agent pembrolizumab. Dr. Reiss and colleagues concluded that patients with refractory HGG had low response rates, with a small number having prolonged PFS. Patients, even those receiving concomitant therapy, tolerated pembrolizumab with few serious AEs.
Dr. R. Donald Harvey and colleagues presented “Enrollment into Molecular Selection Trials and Impact on Patient Disposition” (J Clin Oncol 35, 2017 [suppl, abstract e14035]). Optimal use of molecularly targeted therapies is achieved by pairing agents with driver mutations present in tumor tissue. Enrollment in clinical trials to demonstrate this objective requires obtaining informed consent prior to tumor molecular analysis. Delays can occur in tissue acquisition, testing results, and treatment initiation. Dr. Harvey and colleagues reviewed their experience and patient disposition with studies where assignment to treatment required mutation data. Trials were identified that required consent prior to tissue mutational analysis. Review included time intervals between landmark events, starting with trial presentation to patient, consent, tissue shipment, mutation analysis results, and if and when treatment was initiated. Demographic data, change in Eastern Cooperative Oncology Group performance status (PS), and subsequent therapy were also collected. Patients were included if they signed consent forms. The median age was 60 years (range 32–87); gender: 56% female; race: 72% White, 24% African American, 4% Asian. Most common cancers were lung (35%), colorectal (18%), parotid (7%), and sarcoma (7%). Nineteen patients required new biopsies; 15 patients (22%) discontinued participation before the molecular results were available. Reasons for discontinuation included insufficient archival tissue, loss to follow-up, initiation of other treatment, and death. For the 53 patients who continued: overall mediation time from consent to test results received was 41 days (range 12–149); with median time from consent to obtaining tissue of 22 days (range 0–121), and tissue sent to results received was 13 days (range 1–77). In those with advanced disease (n = 36), PS worsening occurred in 28%. Three patients were matched to therapy; 1 received more than one cycle. In those not matching (n = 50), 46% received approved therapies, 22% were lost to follow-up, 18% enrolled in another trial, and 14% died. In conclusion, enrolling patients into molecular-based treatment trials requires additional time and resources, and many patients do not have driver mutations. The long intervals between decision points can delay therapies and impair the ability to explore alternative treatment.
Additional research by HOPA members reported in conjunction with the 2017 ASCO Annual Meeting is listed below.
Dr. Lisa M. Cordes
“A Phase I Study of Cabozantinib plus Nivolumab (CaboNivo) and CaboNivo plus Ipilimumab (CaboNivoIpi) in Patients (pts) with Refractory Metastatic (M) Urothelial Carcinoma (UC) and Other Genitourinary (GU) Tumors” (J Clin Oncol. 35, 2017 [suppl: abstr 4562]
"Avelumab in Metastatic Castration-Resistant Prostate Cancer (mCRPC)” (J Clin Oncol. 35, 2017 [suppl: abstr 5037])
“Preliminary Results from a Phase 1 Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGF-β, in Advanced Solid Tumors” (J Clin Oncol. 35, 2017 [suppl; abstr 3006])
Dr. R. Donald Harvey
“Phase IB Study of Induction Chemotherapy with XELOX, Followed by Radiation Therapy, Carboplatin, and Everolimus in Patients with Locally Advanced Esophageal Cancer (EC)” (J Clin Oncol. 35, 2017 [suppl; abstr e15607])
“GCT1021-01, a First-in-Human, Open-Label, Dose-Escalation Trial with Expansion Cohorts to Evaluate Safety of Axl-Specific Antibody-Drug Conjugate (HuMax-Axl-ADC) in Patients with Solid Tumors (NCT02988817)” (J Clin Oncol. 35, 2017 [suppl; abstr TPS2605])
Dr. Patrick Kiel
“Clinical Implementation of Whole Genome Multi-Omics Analyses for Patients with Refractory Cancers” (J Clin Oncol. 35, 2017 [suppl; abstr 1531])
Dr. John G. Kuhn
“Metformin to Treat Prostate Cancer (PCa) and Prevent Metabolic Syndrome Associated with Androgen Deprivation Therapy (ADT): Results of A Randomized Double-Blind Placebo-Controlled Study of Metformin in Non-Diabetic Men Initiating ADT for Advanced PCa” (J Clin Oncol. 35, 2017 [suppl; abstr e 16502])
Dr. Cindy O’Bryant
“Safety and Pharmacokinetics of Crizotinib in Patients (pts) with Hepatic Impairment (HI) and Advanced Cancer” (J Clin Oncol. 35, 2017 [suppl; abstr 2552])
Dr. Ming Poi
“Phase Ib Study of Heat Shock Protein 90 Inhibitor, Onalespib in Combination with Paclitaxel in Patients with Advanced, Triple-Negative Breast Cancer (NCT02474173)” (J Clin Oncol. 35, 2017 [suppl; abstr TPS1127])
Dr. Hai T. Tran “Local Consolidation Therapy (LCT) after First Line Tyrosine Kinase Inhibitor (TKI) for Patients with EGFR Mutant Metastatic Non-Small Cell Lung Cancer (NSCLC)” (J Clin Oncol. 35, 2017 [suppl; abstr e20654])