Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US.

Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum's deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): a comparison of VRd, KRd, and IRd.

Lack of head-to-head trials highlights a need for comparative real-world evidence of proteasome inhibitors plus Rd.Methods: In this retrospective, US population-representative EHR study of RRMM patients initiating IRd, KRd, or VRd in line of therapy (LOT) ≥2 between 1/2014 and 9/30/2018, 664 patients were treated in LOT ≥2 with: IRd, n = 168; KRd, n = 208; VRd, n = 357. Median age was 71/65/71 years; 67%/70%/75% had a frailtymodified score of intermediate/frail; 20%/28%/13% had high cytogenetic risk in I-/K-/V-Rd groups. Risk of PI-triplet discontinuation was lower for I- vs. K-Rd (HR: 0.71) and I- vs. V-Rd (HR: 0.85); unadjusted, median TTNTs (months): 12.7/8.6/14.2 (LOT ≥2) and 16.8/9.5/14.6 (LOT 2-3) (I-/K-/V-Rd). Adjusted TTNT was comparable between I-/K-/V-Rd in LOT ≥2 with a TTNT benefit among intermediate/frail patients for I- (HR: 0.70; P=0.04) and V- (HR: 0.73; P<0.05) vs. K-Rd. I/K/V-Rd triplets were comparable in TTNT overall, but IRd and VRd were associated with longer TTNT in intermediate/frail patients than KRd. The results suggest a trial-efficacy/real-world-effectiveness gap, especially for KRd, underlining the limited generalizability of trial results where >50% of patients are excluded. Individualized treatment based on patient characteristics, such as frailty status, is especially pertinent in an elderly RRMM population.

Randomized Clinical Trial Representativeness and Outcomes in Real-World Patients: Comparison of 6 Hallmark Randomized Clinical Trials of Relapsed/Refractory Multiple Myeloma.

BACKGROUND: Concern has been increasing in oncology regarding randomized clinical trial (RCT) eligibility limiting the generalizability of the findings to real-world populations. Using a large US electronic health record database, we investigated the real-world generalizability of the findings from recent RCTs for relapsed and/or refractory multiple myeloma (RRMM). PATIENTS AND METHODS: Patients with RRMM initiating second-to fourth-line therapy with the control arm of the following RCTs were retrospectively identified and categorized as "RCT eligible" or "RCT ineligible" according to the eligibility criteria: (1) Rd (lenalidomide, dexamethasone)-ASPIRE, TOURMALINE-MM1, POLLUX, and ELOQUENT-2; and (2) Vd (bortezomib, dexamethasone)-CASTOR and ENDEAVOR. Predictors of RCT ineligibility and overall survival were analyzed using logistic regression and Cox regression analysis. RESULTS: Variations in the individual trial ineligibility rates were noted, with up to 72.3% (range, 47.9%-72.3%) of patients not meeting the eligibility criteria for 1 of the 6 hallmark RCTs (n = 788 for Rd; n = 477 for Vd). Other malignancies, cardiovascular disease, acute infection, and renal dysfunction were the common reasons for ineligibility. Advanced age, Charlson comorbidity score of ≥ 2, later therapy lines (3-4), and refractory status to the previous line were independently predictive of RCT ineligibility. RCT-ineligible versus RCT-eligible patients had a significantly greater mortality risk (hazard ratio, Rd, 1.46; Vd, 1.51). CONCLUSION: Most real-world patients with RRMM were ineligible for the hallmark RCTs. The eligibility rates varied across the RCTs, underlining the flawed nature of cross-study comparisons without RCT validation. Overall survival was significantly affected by the inability to meet the criteria, highlighting the limited generalizability of the RCT results. Greater efforts are required to broaden the eligibility criteria to reflect real-world clinical characteristics and narrow the gap between RCT efficacy and the observed effectiveness in real-world patients with RRMM.

Cost differential of immuno-oncology therapy delivered at community versus hospital clinics.

OBJECTIVES: The site of cancer care delivery has been shown to be associated with the total cost of care. The magnitude of this effect in patients receiving expensive immuno-oncology (I-O) therapies has not been evaluated. We evaluated cost differentials between community-based and hospital-based outpatient clinics among patients receiving I-O therapies. STUDY DESIGN: This was a retrospective analysis utilizing Truven MarketScan Commercial and Supplemental Medicare claims databases. METHODS: Cost data for 3135 patients with non-small cell lung cancer, squamous cell carcinoma of the head and neck, bladder cancer, renal cell carcinoma, or melanoma who received pembrolizumab, nivolumab, and/or ipilimumab between January 1, 2015, and February 14, 2017, were analyzed as cost per patient per month (PPPM). Patients treated within a community setting were matched 2:1 with those treated at a hospital clinic based on cancer type, specific I-O therapy, receipt of radiation therapy, evidence of metastatic disease, gender, age, and evidence of surgery in the preindex period. RESULTS: Mean (SD) total (medical plus pharmacy) PPPM cost was significantly lower for patients treated in a community- versus hospital-based clinic ($22,685 [$16,205] vs $26,343 [$22,832]; P <.001). Lower PPPM medical cost in the community versus hospital setting ($21,382 [$15,667] vs $24,831 [$22,102]; P <.001) was the major driver of this cost differential. Lower total cost was seen regardless of cancer type or I-O therapy administered. CONCLUSIONS: Treatment with I-O therapies in community practice is associated with a lower total cost of care compared with that in hospital-based outpatient practices. With the expanding indications of these agents, future research is needed.

A retrospective study evaluating treatment patterns and survival outcomes in elderly patients with acute myeloid leukemia treated in the United States with either 7+3 or a hypomethylating agent.

Intensive treatment for newly diagnosed acute myelogenous leukemia (ND-AML) patients are reserved for "fit" patients. While guidelines recommend evaluation of age, performance status and comorbidities, there is no consensus on the definition of "fitness" or optimal therapy for elderly AML patients. This retrospective study evaluated characteristics and survival outcomes of 274 patients (age ≥60 years) with ND-AML treated with 7 + 3 (cytarabine + an anthracycline) vs. hypomethylating agents (HMAs). Most patients received 7 + 3 (60.2%) vs. HMAs (39.8%) in first-line therapy (1 L T); more HMA patients were ≥75 years old and had more comorbidities. Median progression-free survival (PFS) following 1 L T was longer for patients who received 7 + 3 vs. HMAs (6.7 months [95% confidence interval (CI)]: 4.9, 11.1) vs. 4.1 months (95% CI: 2.8, 4.9, respectively). Median overall survival (OS) following 1 L T was also longer for patients who received 7 + 3 vs. HMAs (14.7 months [95% CI: 11.0, not estimated] vs. 4.3 months [95% CI: 3.2, 5.8], respectively). An age-adjusted Charlson Comorbidity Index score of ≥4 vs. < 4 negatively affected PFS and OS irrespective of treatment. Overall, choosing an HMA over 7 + 3 in elderly patients with ND-AML may be influenced by age and comorbidities; patients receiving 7 + 3 had longer survival than those on an HMA.

Realized and Projected Cost-Savings from the Introduction of Generic Imatinib Through Formulary Management in Patients with Chronic Myelogenous Leukemia.

BACKGROUND: Imatinib, a first-generation tyrosine kinase inhibitor (TKI), and the newer second-generation TKIs have dramatically improved outcomes for patients with chronic myelogenous leukemia (CML). A previous model estimated the potential cost-savings over the next 2 years after the loss of patent exclusivity for imatinib in the United States in 2016 and its availability in a generic form. Payers have indeed realized meaningful savings, but it took 2 years for the prices of generic imatinib to decline substantially. OBJECTIVE: To quantify the cost-savings for a US health plan from the passive substitution of generic imatinib and the impact of step-edit therapy with the use of generic imatinib before coverage of a second-generation TKI. METHODS: We updated the previously published model utilizing hypothetical 1-million-member commercial and Medicare plans to include current TKI use and pricing combined with recent epidemiologic data. Regression models were used to project utilization to 5 years after the loss of imatinib's patent exclusivity. We compared generic imatinib costs with a scenario in which generic imatinib was not available. The impact of a step-edit therapy restriction was explored for patients with incident CML. The analyses were repeated for the entire US population based on national census data. RESULTS: The 1-million-member commercial plan saved $0.5 million (3%) from pharmacy spending on TKIs in year 1 and $3.9 million (19%) in year 2 after the loss of patent exclusivity. The projected savings significantly increased to $7.8 million (37%), $8.3 million (39%), and $8.6 million (40%) in years 3, 4, and 5, respectively. Step-edits strategies were projected to result in small incremental savings of $0.3 million (1.5%) annually in years 3 to 5. The 1-million-member Medicare plan saved $1.7 million (3%) in year 1 and $14.1 million (19%) in year 2. The projected savings were $27.8 million (37%), $29.5 million (39%), and $30.8 million (40%), with step-edit estimated to add only $0.9 million (1.2%) annually in years 3 to 5. Generic imatinib saved US payers $2.5 billion (13% of the total spending on TKIs) in years 1 and 2. In years 3 to 5, the cumulative projected savings totaled $12.2 billion, and the savings were expected to grow to 39% as a result of passive generic imatinib substitution, with only 1.7% additional savings from step-edit restriction. CONCLUSIONS: As a result of a lower price for generic imatinib relative to the brand-name version of the drug, substantial cost-savings to US payers over the next 3 years are expected without step-edit formulary management restrictions. Cost-saving strategies, including formulary management restrictions, should adhere to evidence-based guidelines to ensure the appropriate use of generic imatinib and all available TKIs, with the objective to maintain positive outcomes and, in turn, increase the value of patient care.

Transfusion-free interval is associated with improved survival in patients with higher-risk myelodysplastic syndromes engaged in routine care.

Most higher-risk myelodysplastic syndrome (HR-MDS) patients will become transfusion-dependent, leading to potential complications, including infections or end-organ dysfunction. Data correlating achievement of transfusion-free intervals (TFIs) during first-line therapy (1LT) with survival are sparse. We evaluated HR-MDS patients receiving 1LT diagnosed from 1/1/2008 to 7/31/2015 and the impact of a TFI (≥60-day interval without transfusions) on progression-free and overall survival (PFS, OS) using Cox proportional-hazard models. Two hundred and twenty-nine HR-MDS patients received 1LT; overall, median PFS/OS were 8.4 months and 14.7 months, respectively. Two-year PFS/OS were 22.3% and 34.6%, respectively. Median PFS/OS were longer for patients with vs. without a TFI (16.9 vs. 6.1 months and 26.1 vs. 11.8 months, respectively; p < .01 [both]). Two-year PFS (43.0% vs. 3.9%; p < .01) and 2-year OS (51.8% vs. 22.5%; p < .01) were also longer in patients with a TFI vs. not. Achievement of a TFI during 1LT appears to positively affect PFS and OS in HR-MDS patients.

Economic Burden of Patients Treated for Higher-Risk Myelodysplastic Syndromes (HR-MDS) in Routine Clinical Care in the United States.

BACKGROUND AND OBJECTIVE: Significant clinical burden is associated with higher-risk myelodysplastic syndromes (HR-MDS); however, the economic burden has not been fully examined. We examined cost of care and healthcare utilization (HCU) in HR-MDS patients engaged in routine care in the United States (US). METHODS: Adult US patients diagnosed with HR-MDS from 1/1/2008 to 10/31/2015 were identified from the Optum database. Patients were followed until death, progression to acute myeloid leukemia (AML), end of enrollment, or end of study (12/31/2015). Myelodysplastic syndrome (MDS)-related costs/HCU (including medical/pharmacy claims with a primary diagnosis of MDS, MDS-related treatment, or supportive care) and non-MDS-related costs/HCU were evaluated. Costs were calculated as per-patient per-month (PPPM) costs adjusted to 2015 US dollars. RESULTS: Of the 209 HR-MDS patients included, median follow-up was 9.9 months (interquartile range 4.6-17.9), and 69.4% had at least one inpatient admission, 56.9% had at least one emergency department visit, and nearly all patients had at least one outpatient visit. Average PPPM costs over follow-up were $17,361; year 1 versus year 2 costs were higher ($17,337 vs $12,976) following HR-MDS diagnosis. The majority of costs were for MDS-related medical services ($10,327 PPPM). MDS-related medical PPPM costs decreased from $10,557 (year 1) to $6530 (year 2). The main drivers of MDS-related medical costs and the decrease in year 2 were chemotherapy and supportive care costs. CONCLUSIONS: The economic burden of HR-MDS is considerable, particularly within the first year of diagnosis. Treatment/supportive care costs accounted for a significant portion of MDS-related costs. As HR-MDS treatment evolves, the economic impact and HCU need to be further investigated.

Adoption of triplet therapy and clinical outcomes in routine practice among newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant in the USA.

BACKGROUND: Immunomodulator (IMID) and proteasome inhibitor (PI) triplet frontline therapy (FT) in newly diagnosed multiple myeloma (NDMM) trials improve overall survival (OS); reported outcomes in routine practice are lacking. Authors compared outcomes in NDMM patients in the USA by use of triplet vs doublet FTs. METHODS: In this retrospective study of NDMM patients without FT transplant between 1/1/2008 and 6/30/2017, FT was categorized as: PI+IMID-triplet (≥ 3 drugs including PI+IMID), non-PI+IMID-triplet (≥ 3 drugs, not PI+IMID), doublet (≤ 2 drugs). Univariate and multivariate analyses identified FT triplet predictors and compared time-to-next-treatment (TTNT)/OS. RESULTS: Among 4,982 NDMM patients, 68% and 32% initiated doublet and triplet FTs (PI+IMID: 36% in 2017). Triplet FT predictors included: age, cytogenetics, ISS stage, certain CRAB symptoms. Median TTNTPI+IMID-triplet = 18.9 months vs 13.7 (non-PI+IMID-triplet) and 16.5 months (doublet) FTs (P< 0.01); adjusted HRPI+IMID-triplet = 0.86; P= 0.009; HRnon-PI+IMID-triplet = 1.10; P = 0.083 vs doublet FT. Median OSPI+IMID-triplet = 58.7 months vs 43.6 (non-PI+IMID-triplet) and 45.7 months (doublet) FTs (P< 0.01); adjusted HRPI+IMID-triplet = 0.83; P= 0.016; HRnon-PI+IMID-triplet = 1.02; P = 0.727 vs doublet FT. CONCLUSION: PI+IMID-triplet FT is not utilized for most non-frontline-transplant NDMM patients in routine care but is associated with prolonged TTNT/OS.

Cost Differences Associated With Oncology Care Delivered in a Community Setting Versus a Hospital Setting: A Matched-Claims Analysis of Patients With Breast, Colorectal, and Lung Cancers.

PURPOSE:: Access to high-quality cancer care remains a challenge for many patients. One such barrier is the increasing cost of treatment. With recent shifts in cancer care delivery from community-based to hospital-based clinics, we examined whether this shift could result in increased costs for patients with three common tumor types. METHODS:: Cost data for 6,675 patients with breast, lung, and colorectal cancer were extracted from the IMS LifeLink database and analyzed as cost per patient per month (PPPM). Patients treated within a community setting were matched (2 to 1) with those treated at a hospital clinic on the basis of cancer type, chemotherapy regimen, receipt of radiation therapy, presence of metastatic disease, sex, prior surgery, and geographic region. Approximately 84% of patients were younger than 65 years of age. RESULTS:: Mean total PPPM cost was significantly lower for patients treated in a community- versus hospital-based clinic ($12,548 [standard deviation {SD}, $10,507] v $20,060 [SD, $16,555]; P < .001). The PPPM chemotherapy cost was also significantly lower in the community setting ($4,933 [SD, $4,983] v $8,443 [SD, $10,391]; P < .001). The lower cost observed in community practice was irrespective of chemotherapy regimen and tumor type. CONCLUSION:: We observed significantly increased costs of care for our patient population treated at hospital-based clinics versus those treated at community-based clinics, largely driven by the increased cost of chemotherapy and provider visits in hospital-based clinics. If the site of cancer care delivery continues to shift toward hospital-based clinics, the increased health care spending for payers and patients should be better elucidated and addressed.

Economic burden of elderly patients with acute myeloid leukemia treated in routine clinical care in the United States.

This retrospective claims database study examined healthcare utilization (HCU) and costs associated with acute myeloid leukemia (AML) in 237 elderly patients who received chemotherapy or a stem cell transplant (SCT) following AML diagnosis. Patients with secondary AML were excluded. Over the entire follow-up period, 92.0% of patients had ≥1 inpatient admission; 85.7% had ≥1 AML-related admission, and 42.6% had ≥1 non-AML-related admission. During inpatient admissions, 39.2% of patients had ≥1 intensive care unit (ICU) admission, with 20.7% having ≥1 AML-related ICU admission, and 27.8% having ≥1 non-AML-related ICU admission. Total mean per-patient per-month (PPPM) costs over the follow-up period were $25,243 (SD: $21,909), with costs from Year 1 ($27,756 [SD: $22,121]) more than double those in Year 2 ($12,953 [SD: $26,334]) following AML diagnosis. The majority of total costs were medical ($24,512 PPPM [SD: $21,704]), which included inpatient admissions ($6548 PPPM [SD: $10,777]), other outpatient visits ($5021 PPPM [SD: $7997]), supportive care ($3640 PPPM [SD: $5589], and chemotherapy administration ($2029 PPPM [SD: $2345]). Healthcare costs of treated elderly AML patients are substantial, particularly in the first year following diagnosis. Further research is needed to understand factors contributing to high costs in various settings of care for elderly AML patients.

Prolonged Duration of Therapy Is Associated With Improved Survival in Patients Treated for Relapsed/Refractory Multiple Myeloma in Routine Clinical Care in the United States.

BACKGROUND: In clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second-line therapy on overall survival. PATIENTS AND METHODS: Adults with NDMM from January 2008 to June 2015 were followed up to identify their second-line therapy. The duration of therapy (DOT) and time to next therapy (TTNT), as a proxy for progression-free survival, were estimated using the Kaplan-Meier method. The relationship between the duration of second-line therapy and overall survival was evaluated with a logistic marginal structural model to mitigate the risk of treatment selection and survival bias. RESULTS: A total of 628 NDMM patients developed a relapse after initial therapy. The median DOT for second-line therapy was 6.9 months (95% confidence interval [CI], 5.9-7.7 months), which was shorter than the corresponding TTNT (median, 15.1 months; 95% CI, 13.4-17.3 months). Each additional month of second-line therapy was associated with a reduced adjusted risk of death at 1 year (odds ratio, 0.78; 95% CI, 0.77-0.83; P < .001). CONCLUSION: In a large database capturing a heterogeneous patient population and varied treatment patterns reflecting routine clinical care, we found a clinical benefit for continued longer DOT at first relapse. Despite the emerging paradigm favoring continuous therapy, second-line progression-free survival (utilizing TTNT as the proxy) was more than twofold longer than the DOT. Understanding the barriers to extended DOT could help to improve the outcomes for RRMM patients.

The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies.

OBJECTIVES: One-third of patients with multiple myeloma (MM) are diagnosed at age≥75years. Older patients have increased incidence of cardiovascular disease (CVD) and renal insufficiency (RI), hallmark complications of MM. We examined cumulative incidence of CVD and RI in relapsed/refractory MM (RRMM) and outcomes by age and RI/CVD. MATERIALS AND METHODS: Retrospective cohort study using a large US electronic medical records database of adult patients with RRMM initiating first- and second-line therapy (2LT) between 1/2008-06/2015. RI and CVD comorbidities were based on diagnosis codes and/or lab values. RESULTS: Among 628 patients, 37.1% were ≥75years. Cumulative incidence of CVD and/or RI increased from 47.7% at MM diagnosis to 67.8% at first relapse. Age≥75years had a trend toward higher risk of relapse post 2LT, proxied by time to next treatment (TTNT), (adjusted HR: 1.28; 95% CI: 1.00, 1.65; P=0.05). TTNT was significantly higher with comorbid CVD+RI (adjusted HR: 1.50; 95% CI: 1.11, 2.02; P<0.01). Age≥75years, RI, CVD, and CVD+RI were associated with increased mortality risk from 2LT initiation; adjusted HR: 1.66 (95% CI: 1.19, 2.33; P<0.01), 1.51 (95% CI: 1.01, 2.26; P=0.04), 1.75 (95% CI: 1.03, 2.96; P=0.04), and 1.95 (95% CI: 1.29, 2.93; P<0.01), respectively. CONCLUSION: Despite treatment with novel agents for RRMM in 86% of patients, an outcome gap persists for older patients and those with RI and/or CVD. Personalized treatment approaches that account for age and comorbidities, and further evaluation of innovative regimens and dosing schedules, are needed to improve outcomes for these patients.

A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis.

BACKGROUND: Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is associated with significant toxicities, leading to a high rate of drug discontinuation. We implemented a modified regimen of gemcitabine and nab-paclitaxel (mGNabP) in an attempt to minimize toxicities while maintaining efficacy. METHODS: A total of 79 evaluable patients with metastatic pancreatic adenocarcinoma (mPC) treated with a modified regimen of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 15 of every 28-day cycle were identified from our prospective database. A total of 57 patients received this regimen as first-line treatment and were evaluated for toxicities, progression-free survival (PFS), and overall survival (OS). Overall, 22 patients with advanced or metastatic PC treated with the modified regimen outside the first-line setting were only evaluated for toxicities. RESULTS: The median OS and PFS were 10 months [95% confidence interval (CI) 5.9-13 months] and 5.4 months (95% CI 4.1-7.4 months) for patients that received the modified regimen as first-line therapy. Neurotoxicity occurred in 27% with only 1.6% of patients experiencing grade ⩾3 toxicity. The incidence of grade ⩾3 neutropenia was 19%, resulting in growth factor support in 12% of patients. This rate was similar in patients who received the modified regimen for first-line treatment of mPC versus the overall group. CONCLUSIONS: A modified regimen of biweekly nab-paclitaxel with gemcitabine is associated with a lower cost, acceptable toxicity profile and appears to be relatively effective in pancreatic cancer. Prospective randomized studies confirming its potential benefits compared with standard weekly mGNabP are warranted.

Unintended Consequences in Cancer Care Delivery Created by the Medicare Part B Proposal: Is the Clinical Rationale for the Experiment Flawed?

PURPOSE: Medicare currently enrolls ≥ 45 million adults, and by 2030 this is projected to increase to ≥ 80 million beneficiaries. With this growth, the Centers for Medicare & Medicaid Services (CMS) issued a proposal, the Medicare Part B Drug Payment Model, to shrink drug expenditures, a major contributor to overall health care costs. For this to not adversely affect patient outcomes, lower-cost alternative medications with equivalent efficacy and no increased toxicity must be available. This is often not true in the treatment of cancer. Herein, we examine the flaws in the rationale of the CMS and the potential unintended consequences of this experiment. METHODS: We identified the top three oncology expenditures (rituximab, bevacizumab, and trastuzumab) and their vetted alternatives (per the National Comprehensive Cancer Network guidelines) to ascertain whether lower-cost equivalent alternatives are available. Drug cost was based on April 2016 average sale price. We explored both efficacy of the agents and, when applicable, toxicity to compare alternatives to these high-dollar medications. RESULTS: For the largest Medicare oncology drug expenditures, there is not a lower-cost option with equal efficacy for their primary indications. Without lower-cost alternatives, the unintended consequence of this CMS experiment may include curtailing access to care or an increase in patient/program costs. CONCLUSION: The CMS proposal, by simply lowering reimbursement for drugs, does not acknowledge the value of these agents and could unintentionally reduce quality of care. Alternative approaches to value-based care, such as the Oncology Care Model and similar frameworks, should be explored.

Biweekly gemcitabine and low-dose cisplatin in the treatment of locally advanced or metastatic pancreatic cancer patients: a single institute experience.

Gemcitabine in combination with low-dose cisplatin has shown promising activity in pancreatic cancer with manageable toxicities. The purpose of this study is to assess the activity of a combination of gemcitabine and low-dose cisplatin in the first-line treatment of metastatic and locally advanced pancreatic cancer patients. We conducted a retrospective analysis of all patients diagnosed with metastatic and locally advanced pancreatic cancer who received a combination of gemcitabine and cisplatin in the first-line setting. Patients with baseline cytopenias and elevated liver function tests were included. Patients received cisplatin at 20 mg per square meter followed by gemcitabine at a dose of 1000 mg per square meter at fixed dose rate every 2 weeks. Patients were treated until disease progression or unacceptable toxicities. A total of 58 patients were included in the analysis. The median progression-free survival was 4.4 months [95 % confidence interval (CI) 3.6-6.4], and median overall survival was 6.7 months (95 % CI 4.4-10.9). Thirty-eight patients (66 %) experienced at least one grade 3 or 4 toxicity. The most common grade 3 or 4 toxicity was hematologic toxicity (25 patients, 43 %). Biweekly fixed dose rate gemcitabine combined with low-dose cisplatin shows interesting activity in advanced pancreatic cancer. This regimen is an acceptable alternative for patients ineligible for gemcitabine plus nab-paclitaxel (i.e., those with elevated bilirubin at baseline) or clinical trials. Additionally, this regimen should be considered as a first-line option for those patients with breast cancer susceptibility gene mutations (BRCA1 and/or BRCA2).

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas.

BACKGROUND: For patients with metastatic pancreatic cancer, FOLFIRINOX (fluorouracil [5-FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) has shown improved survival rates compared with gemcitabine but with significant toxicity, particularly in patients with a high tumor burden. Because of reported response rates exceeding 30 %, the authors began to use a modified (m) FOLFIRINOX regimen for patients with advanced nonmetastatic disease aimed at downstaging for resection. This report describes their experience with mFOLFIRINOX and aggressive surgical resection. METHODS: Between January 2011 and August of 2013, 43 patients with borderline resectable pancreatic cancer (BRPC, n = 18) or locally advanced pancreatic cancer (LAPC, n = 25) were treated with mFOLFIRINOX (no bolus 5-FU, no LV, and decreased IRI). Radiation was used based on response and intended surgery. Charts were retrospectively reviewed to assess response, toxicities, and extent of resection when possible. RESULTS: The most common grade 3/4 toxicity was diarrhea in six patients (14 %) with no grade 3/4 neutropenia or thrombocytopenia. Resection was attempted in 31 cases (72 %) and accomplished in 22 cases (51.1 %) including 11 of 25 LAPC cases (44 %). Vascular resection was required in 4 cases (18 %), with R0 resection in 86.4 % of the resections. Complications occurred in 6 cases (27 %), with no perioperative deaths. The median progression-free survival period was 18 months if the resection was achieved compared with 8 months if no resection was performed (p < 0.001). CONCLUSION: Neoadjuvant mFOLFIRINOX is an effective, well-tolerated regimen for patients with advanced nonmetastatic pancreatic cancer. When mFOLFIRINOX is coupled with aggressive surgery, high resection rates are possible even when the initial imaging shows locally advanced disease. Although data are still maturing, resection appears to offer at least a progression-free survival advantage.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting (CINV) remains both a feared side effect of cancer treatment and a focus of many supportive care initiatives/guidelines. The class of medications known as serotonin receptor antagonists (5-HT3RAs) are integral in the prevention of CINV from both moderately and highly emetogenic chemotherapy. Palonosetron (ALOXI(®)), a second-generation 5-HT3RA, has a higher affinity for the 5-HT3 receptor, has a longer half-life and has unique interactions with the 5-HT3 receptor compared with the current first-generation 5-HT3RA such as ondansetron, granisetron, dolasetron and tropisetron. This may allow palonosetron an advantage in control of CINV. This review article examines the available evidence, the pharmacokinetics and the safety and tolerability of palonosetron in the prevention of CINV.

Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy.

PURPOSE: Nausea and vomiting are among the most feared complications of chemotherapy reported by patients. The objective of this study was to establish the overall complete response (CR; no emesis or use of rescue medication 0-120 h after chemotherapy) with either ondansetron- or palonosetron-containing antiemetic regimens in patients receiving highly emetogenic chemotherapy (HEC). METHODS: This was a prospective, open-label, randomized, single-center, pilot study that enrolled patients receiving their first cycle of HEC. Patients were randomized to receive either palonosetron 0.25 mg IV (PAD) or ondansetron 24 mg orally (OAD) on day 1 prior to HEC. All patients received oral aprepitant 125 mg on day 1, then 80 mg on days 2 and 3, and oral dexamethasone 12 mg on day 1, then 8 mg on days 2, 3, and 4. Descriptive statistics were used to summarize the data. RESULTS: A total of 40 patients were enrolled, 20 in each arm. All patients were female, and 39 received doxorubicin/cyclophosphamide chemotherapy for breast cancer. For the primary endpoint, 65 % (95 % CI, 40.8-84.6 %) of patients in the PAD arm and 40 % (95 % CI, 19.1-63.9 %) of patients in the OAD arm achieved an overall CR. CONCLUSIONS: While CR rates for aprepitant and dexamethasone plus palonosetron or ondansetron-containing regimens have been published previously, this is the first documentation of CR rates with these regimens in the same patient population. These results may be used to design a larger, adequately powered, prospective study comparing these regimens.