Shah, Vishal

PURPOSE Globally, cancer drug expenditure exceeds $185 in US dollars (USD) billion, with the United States contributing $75 (USD) billion. Many cancer drug doses are calculated on the basis of body weight or body surface area, which often results in leftover drug in partially used single-dose vials (SDVs). The cost of wasted drug is a huge financial burden on the US health care system. We evaluated the cost savings resulting from the reduction of SDV wastage, achieved through the implementation of automated dose rounding rules in electronic health records (EHRs). METHODS Mayo Clinic implemented automated dose rounding rules within the EHR. These rules were designed to round calculated doses to the nearest SDV if the vial size closely matched the original calculated dose, within a 10% threshold. We assessed doses administered between January 2019 and December 2021, and computed cost-savings, waste reduction, and cost of waste for chemotherapy drugs. RESULTS In 3 years, 36.1% of doses were rounded down, 35.8% were rounded up, and 28.1% were exact doses. By rounding doses down to a vial size, we achieved cost-savings of $39.75 (USD) million and prevented 62,065 SDV of cancer drugs from going to waste. By rounding doses up, we avoided wasting $9.95 (USD) million worth of drugs. However, there were still instances where the rounding fell outside of the 10%, resulting in wasted drugs worth $25 (USD) million. CONCLUSION The substantial burden imposed on patients and the US health care system because of cancer drug wastage is of significant concern. Although the automated dose rounding system represents a partial solution for this issue, a comprehensive approach involves the imperative development of policy and legislative solutions to effectively mitigate the challenges associated with cancer drug waste.

Introduction The treatment of cancer is associated with high risk for toxicity and high cost. Strategies to enhance the value, quality, and safety of cancer care are often managed independently of one another. Oncology stewardship is a potential framework to unify these efforts and enhance outcomes. This landscape survey establishes baseline information on oncology stewardship in the United States. Methods The Hematology/Oncology Pharmacy Association (HOPA) distributed a 38-item survey composed of demographic, institutional, clinical decision-making, support staff, metrics, and technology sections to 675 HOPA members between 9 September 2022 and 9 October 2022. Results Most organizations (78%) have adopted general pharmacy stewardship practices; however, only 31% reported having established a formalized oncology stewardship team. More than 70% of respondents reported implementation of biosimilars, formulary management, and dose rounding as oncology stewardship initiatives in both inpatient and outpatient settings. Frequently cited barriers to oncology stewardship included lack of clinical pharmacist availability (74%), lack of oncology stewardship training (62%), lack of physician/provider buy-in (32%), and lack of cost-saving metrics (33%). Only 6.6% of survey respondents reported their organization had defined “value in oncology.” Lack of a formalized stewardship program was most often cited (77%) as the rationale for not defining value. Conclusions Less than one-third of respondents have established oncology stewardship programs; however, most are providing oncology stewardship practices. This manuscript serves as a call to action for stakeholders to work together to formalize oncology stewardship programs that optimize value, quality, and safety for patients with cancer.

Background: Pharmacist order verification is a critical step in ensuring medication safety for patients. While the second pharmacist verification (SPV) before dispensing anticancer therapies has been a longstanding practice, its continued necessity in the context of modern electronic health systems lacks robust evidence. Objective: This study aimed to assess the frequency of interventions performed by a second pharmacist to determine the ongoing effectiveness of the SPV process. Methods: This retrospective chart review was conducted at the Mayo Clinic, encompassing all anticancer therapy orders that necessitated an SPV. The study period extended from January 1, 2019, to June 30, 2021, and included inpatient and outpatient anticancer orders. The quantification and reporting of alterations made to discrete order fields subsequent to initial pharmacist verification of clinical significance were performed, utilizing the total number of anticancer therapy orders as the denominator. Results: Approximately 300 000 anticancer therapy orders were screened for inclusion criteria and 2.6% (N = 7634) of orders were modified on the SPV. Most changes were in the categories of rate (N = 1962), order start time (N = 1219), and pharmacy communication note (N = 777). Dosing changes greater than 10% accounted for 0.03% (N = 99) of the orders, with 10 anticancer therapies responsible for more than 50% of these changes. Conclusion and relevance: This study represents the largest report on the impact of SPV in a modern era. Our results suggest the SPV may be valuable for a small proportion of chemotherapy orders but raises questions about the necessity for broad application of this practice.

PURPOSE Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was –0.06 months (95% CI, –5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, –4.02 to 8.48; P = .48) for OS. CONCLUSION Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Objective: This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation. Data Synthesis: The literature search to identify clinical trials returned only the CHRYSALIS phase 1 study. In a phase I trial, amivantamab-vmjw was associated with an overall response rate (ORR) of 40% (95% CI, 29–51) in the EGFR exon20ins NSCLC patient population (n = 81) after platinum-based chemotherapy. There were 3 complete responses (CRs) and 29 partial responses (PRs). The median duration of response (DOR) was 11.1 months (95% CI, 6.9—not reached; NR). The median progression-free survival (PFS) was 8.3 months (95% CI, 6.5–10.9), and overall survival (OS) was 22.8 months (95% CI, 14.6—NR). Application to Clinical Practice: This review summarizes the pharmacology, clinical evidence, and use of amivantamab-vmjw for patients with locally advanced or metastatic NSCLC with EGFR exon20ins mutation. Conclusion: The FDA approval of amivantamab-vmjw, the first bispecific antibody to target the exon20ins mutation, represents an important advancement in the treatment of patients with NSCLC with limited effective treatment options. The initial findings of the CHRYSALIS trial demonstrate an overall tumor response benefit with an acceptable safety profile.

8 Background: At Mayo Clinic, the implementation of an automated chemotherapy dose rounding program has resulted in significant cost savings when doses are rounded down to a vial size, however, the cost burden from drug waste continues to be a significant issue when rounding to a vial size is not within our 10% rounding allowance. The mismatch between drug doses and the marketed vial sizes, along with the limitations to the use of single dose vials is a recognized problem, resulting in billions of dollars of wasted drugs in the United States.The goal of our study was to quantify the cost of the wasted amount of chemotherapy and biologic drugs after the implementation of an automated dose rounding program. Methods: Using the electronic health record (EHR), data was collected for biologic and oncolytic agents administered from 1/1/2019 through 12/31/2021. Drugs with waste documented during preparation and that were administered to cancer patients were selected for analysis. The % of doses with waste documented was calculated based upon the total number of all doses given. The total cost of the drug administered along with the cost of the amount of drug wasted were calculated based upon costs listed in the EHR at the time of administration. Results: For the 3-year period, 446,832 doses were dispensed with 47,626 (10.7%) of those doses having waste documented. The total cost of the drugs with documented waste was $114,323,203 with 21.9% ($25,086,608) accounting sole for wasted drug. Five drugs accounted for 59% of the total cost of the drug waste (Table). When examining individual drugs with a high % of doses with documented waste, methoxsalen, epirubicin, eribulin, topotecan, & bortezomib each had > 70% of doses with a documented wasted amount. Conclusions: Despite having an aggressive institutional dose rounding policy, drug waste still results in considerable and significant costs to the Mayo Clinic System. Our data likely underestimates the total cost of drugs waste given that waste documentation requires manual entry into the EHR at the time of preparation. Our results support the need to create and develop solutions that could lead to reduced waste costs which include re-examining the weight based dosing of drugs, mandating pharmaceutical companies to have vial sizes that more appropriately meet the range of standard dosing, developing more multi-dose vials that can be shared across multiple patients, utilizing closed-system transfer devices to extend beyond-use-dating time, or requiring pharmaceutical companies to reimburse payers and patients for the cost of the amount wasted. Drug waste is still a considerable issue and one that needs to be addressed at a policy level.[Table: see text]

Objective: To review the new indication of cyclin-dependent kinase (CDK4/6) inhibitor abemaciclib for the adjuvant treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−), axillary lymph node (LN) positive early breast cancer (EBC) at high risk of recurrence and a Ki-67 ≥20%. Data Sources: A literature search was performed through PubMed, ClinicalTrials.gov, and Food and Drug Administration (FDA) website (February 1, 2018, to December 23, 2021) to identify relevant information. Study Selection and Data Extraction: Human and animal studies related to pharmacology, pharmacokinetics, efficacy, and safety of abemaciclib were identified. Data Synthesis: Addition of abemaciclib to standard of care endocrine therapy (ET) for patients with high-risk clinicopathologic features and Ki-67 ≥20% demonstrated 30% reduction in the risk of developing invasive disease and distant recurrence. At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01). At 27 months, IDFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.82, P < 0.0001). Diarrhea occurred in more than 80% of patients in the abemaciclib arm. Relevance to Patient Care and Clinical Practice: This review describes the clinical applicability of adjuvant abemaciclib for patients with HR+, HER2− EBC at high risk for recurrence. Conclusion: Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2− node positive EBC. Longer follow-up is needed to determine the impact of adjuvant abemaciclib on late disease recurrence and survival outcomes.

Abstract Purpose To decrease drug waste and cost by implementing automated chemotherapy dose rounding rules in the electronic health record (EHR). Dose rounding of chemotherapy is a recognized method for reducing drug waste, and professional organizations have published guidelines recommending dose rounding when possible. Summary On the basis of current literature and guideline recommendations, Mayo Clinic developed system-wide consensus to allow dose rounding for biologic and chemotherapy agents to the nearest vial size if rounding resulted in the dose being within 10% of the originally calculated dose or to a convenient measurable volume, based on concentration of the drug, if rounding to the nearest vial size resulted in the dose being outside the 10% range. Oncology pharmacists reviewed and analyzed all drugs listed in the EHR used in injectable form for the treatment of cancer and developed dose rounding rules. The rules were implemented and applied at the dose calculation stage before provider signature. From January to June 2019, approximately 40,000 cancer treatment doses were administered. The rounding rules saved a total of 9,814 vials of drug, of which 5,329 were for biologic agents and 4,485 were for oncolytic drugs. This resulted in a total 6-month cost savings of $7,284,796 (in 2019 dollars; biologics, $5,727,402; oncolytics, $1,557,394). Conclusion Systematic implementation of dose rounding rules utilizing the EHR can result in significant reduction of drug waste and realization of savings.

Abstract Introduction: Hematologic response (HR) particularly complete response (CR) is critical in patients (pts) with AL since it improves overall survival (OS) because of organ response (OrgR). Bor based therapies especially in combination with cyclophosphamide and dexamethasone (CyBorD) have shown to be an active regimen in AL. So far, there have been no comparative studies studying the effect of treatment with B-based regimens prior to SCT (Bor-SCT) versus SCT upfront or SCT preceded by non-Bor therapies (non-Bor-SCT). We present a retrospective analysis of data with an aim to compare the OS, OrgR and HR in the two cohorts. Methods: Charts were reviewed for the pts who underwent SCT for AL since 2004 until 2015 at Mayo Clinic in Arizona. HR and OrgR were determined using the consensus criteria from International Society of Amyloidosis.1 HR were noted at 3, 6 and 12 months from SCT. Results: Patients and disease characteristics: 63 pts were identified who underwent SCT for AL, of which 34 were in Bor-SCT and 29 were in the non-Bor-SCT cohort. Median age at diagnosis was 59.5 (range, 39 - 72) and 63 (range, 38 - 76) years and at SCT was 60 (range, 40 - 72) and 63 (range, 39 - 76) years for Bor-SCT and non-Bor-SCT, respectively. There were 13 (38%) females in Bor-SCT and 9 (31%) in non-Bor-SCT. Mean bone marrow involvement of plasma cells at diagnosis was 18% (SD±16.5) in Bor-SCT and 6.8% (SD±7.8) in non-Bor-SCT (p = 0.004). All pts had an ECOG performance score of better than 3 at the time of SCT. Fifteen (44%) pts had single organ involvement at diagnosis and 9 (26.5%) had 2-organ involvement in Bor-SCT. In non-Bor-SCT, 21 (72%) pts had single and 6 (21%) had 2-organ involvement (p = 0.04). More than 2 organs were involved in 10 (29%) pts in Bor-SCT and 2 (7%) in non-Bor-SCT. Heart was involved in 18 (53%) pts in Bor-SCT and 8 (28%) in non-Bor-SCT (p = 0.04) while kidney involvement was seen in 27 (79%) in Bor-SCT and 23 (79%) in non-Bor-SCT (p = 0.99). Median creatinine was not significantly different in the 2 groups at diagnosis or at the time of SCT. In Bor-SCT, no pts were on hemodialysis at the time of diagnosis or SCT. In non-Bor-SCT, 1 pt at diagnosis and 3 pts at SCT progressed to need hemodialysis. Lambda light chain was involved in 27 (82%) and 22 (76%) (p = 0.56) with a mean level of involved light chains being 59(SD±88.7) g/dL and 43.3 (SD±64.6) g/dL (p=0.4539) in Bor-SCT and non-Bor-SCT, respectively. Treatment: Thirty-one (91%) out of 34 pts in Bor-SCT group got treatment with CyBorD while 2 (6%) got Bor with dexamethasone and 1 (3%) got Bor with pegylated liposomal doxorubicin. In the non-Bor-SCT group, 20 (69%) out of 29 got no treatment, 4 (14%) got melphalan prednisone, 2 (7%) got dexamethasone alone, 1 (3%) got vincristine dexamethasone and 2 (7%) got lenalidomide dexamethasone prior to SCT. Transplant factors: Median time from diagnosis to SCT was 226.5 (range, 65 - 1108) days in Bor-SCT and 150.5 (48 - 1139) days in non-Bor-SCT (p=0.32). Full dose of melphalan (200 mg/m2) was used in 21 (62%) pts in Bor-SCT and 13 (34%) pts in non-Bor-SCT (p <0.001). Mean dose of cells used for SCT was 4.6 (SD±0.9) and 4.8 (SD±2.2) x 106/kg in Bor-SCT and non-Bor-SCT, respectively. Median time to neutrophil and platelet engraftment was 13 (range, 10 - 27) and 16 (range, 8 - 28) days in Bor-SCT while 11 (range, 7 - 16) and 13 (range, 10 - 25) days in non-Bor-SCT. Responses: HR at 3, 6 and 12 months from SCT and OrgR by the time of last follow up is described in table 1. Survival: Median OS was not reached in Bor-SCT as compared to 53.4 months in non-Bor-SCT (p =0.001), Figure 1. Conclusions: Our study suggests a benefit in HR, OrgR as well as OS by reduction of disease burden by Bor-based therapy prior to SCT. This benefit was observed despite a higher percentage of pts with cardiac involvement, more than 2 organ involvement and mean bone marrow plasma cells at diagnosis in Bor-SCT. Currently, it is not standard practice to use Bor-based therapy prior to SCT. A prospective study with larger number of pts would be required to confirm these findings. References: 1. Gertz MA et al. Definition of Organ Involvement and Treatment Response in Immunoglobulin Light Chain Amyloidosis (AL): A Consensus Opinion From the 10th International Symposium on Amyloid and Amyloidosis. Am J Hematol. 2005;79(4):319-328. Disclosures Dueck: Bayer: Honoraria. Mikhael:Abbvie, Celgene, Onyx, Sanofi: Research Funding. Bergsagel:Amgen, BMS, Novartis, Incyte: Consultancy; Novartis: Research Funding. Reeder:Novartis, Millennium, BMS and Celgene: Research Funding. Stewart:celgene: Consultancy. Fonseca:AMGEN: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Bayer: Consultancy; Millennium, a Takeda Company: Consultancy; Millennium, a Takeda Company: Consultancy; AMGEN: Consultancy; BMS: Consultancy; Celgene: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; AMGEN: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Millennium, a Takeda Company: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Millennium, a Takeda Company: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Celgene: Consultancy; BMS: Consultancy; Bayer: Consultancy; Novartis: Consultancy.