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Supplements Managed Care Considerations in Meeting Complex Needs of Patients With Pancreatic Cancer
Current Treatment Landscape and Emerging Therapies for Pancreatic Cancer
Nelly Adel, PharmD, BCOP, BCPS
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Managing the Economic Impact of Advanced Pancreatic Cancer
Scott A. Soefje, PharmD, MBA, BCOP, FCCP
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Managing the Economic Impact of Advanced Pancreatic Cancer

Scott A. Soefje, PharmD, MBA, BCOP, FCCP
Pancreatic cancer is typically diagnosed in the late stage of the disease, making it the fourth leading cause of cancer-related death in the United States. It is also one of the few cancers with an increasing incidence, particularly in the younger population. By 2030, it is expected to become the second leading cause of cancer-related death. Patients with pancreatic cancer encounter monthly medical costs 15 times higher than those without, with costs highest in the later stages of the disease. Treatments for pancreatic cancer include surgery (available to fewer than 20% of newly diagnosed patients) and, for advanced disease, chemotherapy with gemcitabine with nab-paclitaxel or FOLFIRINOX, which can increase overall survival (OS) by a few months. Economic and outcome analyses of clinical data find no significant difference in OS between the 2 regimens, although FOLFIRINOX carries a much higher rate of serious adverse effects, limiting its use to patients with good performance status. In 2017, the FDA approved immunotherapy for patients with microsatellite instability–high or mismatch repair-deficient solid tumors, which occurs in approximately 1% of pancreatic cancer diagnoses. Several immunotherapies and targeted therapies are currently in clinical trials and may significantly alter the trajectory of the disease. However, they typically cost more than $100,000 per year, putting significant strain on payers. Thus, it is important that payers plan now for the potential arsenal of new treatments and identify opportunities to manage their utilization as well as patients with the disease to contain costs.
Am J Manag Care. 2019;25:-S0
Pancreatic cancer is the tenth leading cancer in the United States but the fourth leading cause of cancer-related mortality. With an estimated 44,330 deaths in 2018, the ranking will likely change to the third leading cause of deaths due to cancer, slightly above breast cancer.1 Diagnosis is typically made late in the disease, when the cancer is advanced or has spread to distant parts of the body. Thus, fewer than 20% of patients are eligible for curative surgical treatment.2 Instead, the primary treatment is chemotherapy with or without radiation and, on the horizon, targeted therapy or immunotherapy. Given its late diagnosis, individuals with advanced pancreatic cancer have a very poor prognosis, with a relative 5-year survival rate of 8.5% overall. Even patients diagnosed with local disease (10%) have a 5-year survival rate of just 34.3%.3

Pancreatic cancer is one of the few cancers whose incidence is increasing. Between 2004 and 2013, the incidence rate increased about 1% in whites, although it remained stable in blacks.2 The increase is particularly evident in younger people. An analysis of the National Inpatient Sample database found a 75% increase in the rate of pancreatic cancer discharges between 1997 and 2012 in those aged 18 to 44 years, with an overall increase of 55% in women and 31% in men.4 By 2030, pancreatic cancer is expected to become the second leading cause of cancer-related death in the United States.5

Economic Costs

The most recent analysis of direct medical costs related to the total care of pancreatic cancer is based on 5262 patients with pancreatic cancer in a managed care population matched to 15,786 controls between 2001 and 2010. Mean total all-cause healthcare costs per-member, per-month (PMPM), including office visits, inpatient visits, emergency department (ED) visits, and inpatient stays, were $15,480 versus $1001 for the control group (all P <.001), with inpatient stays the highest cost driver ($9917 PMPM). In addition, costs were significantly higher during treatment for metastatic and advanced cancer compared with the initial treatment phase of nonmetastatic disease ($21,637 vs $10,358; P <.001).6

Inpatient costs, which drive overall costs for treatment, are rising. An analysis of data from 1997 to 2012 in the National Inpatient Sample database found total costs nearly tripled during that time, from $24,000 per hospitalization to $68,000, even as the mean length of stay dropped by 19% (from 9.6 to 7.8 days; P <.001) along with a decrease in inpatient mortality by 6%. The number of hospital discharges also increased (28,862 in 1997 to 36,625 in 2012; P <.001). Surgical treatment was the main driver of cost for locoregional disease, whereas chemotherapy and radiation therapy were the main costs for metastatic disease. Inflation could also account for some of the cost increases. The authors hypothesize that improved care and availability of resources or earlier involvement of palliative care and a quicker transition to hospice in patients with widespread disease could help lower cost.4 However, there is no evidence that patients are transitioning more quickly to palliative care or hospice.

Cost-Effectiveness of Current Therapies

In addition to clinical considerations, oncologists are increasingly faced with considering the cost and cost-effectiveness of available treatments to payers and patients. Thus, understanding the economic impact of current and novel therapies in relation to their clinical efficacy and impact on the patient’s health-related quality of life (QOL) is important.

Gemcitabine (GEM) was approved in 1996 for the treatment of late-stage (III and IV) pancreatic cancer, based on data showing improved survival and clinical benefit as compared with fluorouracil, and it has remained the mainstay of treatment.7 The majority of patients receive first-line treatment with nab-paclitaxel plus GEM,8 which demonstrated a 1.8-month median increase in overall survival (OS) compared with GEM monotherapy in patients with metastatic pancreatic cancer9; or FOLFIRINOX, a cocktail of oxaliplatin, irinotecan, 5FU, and leucovorin, which demonstrated a 4.3-month median increase in OS for patients with metastatic pancreatic cancer compared with GEM monotherapy.10 Patients with BRCA1/2 mutated tumors may benefit from treatment with GEM/cisplatin, and a small number of patients with epidermal growth factor receptor (EGFR) positive tumors may benefit from GEM/erlotinib.11,12 

The choice of primary systemic chemotherapy is based, in part, on the patient’s performance and clinical status given that there have been no head-to-head trials between the 2 regimens. In addition, the major trials for each were conducted in different populations, further limiting any comparisons.9,10

Three small retrospective reviews of real-world patient populations reported differing outcomes. One review of 85 patients with metastatic pancreatic cancer found an increased OS in patients treated with FOLFIRINOX compared with those receiving nab-paclitaxel + GEM, with similar toxicity (FOLFIRINOX 14 months vs 7 months; P <.02). In the nab-paclitaxel + GEM cohort, 48% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 1 or higher compared with 4% of those treated with FOLFIRINOX (P = .01), suggesting, the authors noted, the importance of “appropriately selecting patients with poor ECOG PS who can benefit from GEM plus nab-paclitaxel for an adequate control of disease.”13 A second review of 75 patients, most of whom had ECOG 1 when starting first-line treatment with either FOLFIRINOX or nab-paclitaxel + GEM, found similar progression-free survival (PFS), OS, adverse effects, and treatment-related discontinuation rates between the 2 groups.14

A third analysis of 38 patients with unresectable locally advanced or metastatic pancreatic cancer who received FOLFIRINOX or nab-paclitaxel + GEM as first-line chemotherapy found a significantly higher response rate (RR) and PFS in the nab-paclitaxel + GEM group compared with the FOLFIRINOX cohort (40.9% vs 6.3%, P = .025; 6.5 months vs 3.7 months, P = .031, respectively), with lower rates of drug toxicity in the nab-paclitaxel + GEM group.15

Several economic analyses comparing the 2 have recently been published. In one, a Bucher indirect comparison method was used to estimate the comparative efficacy of each regimen. With no significant difference in OS, total treatment costs were 3.6 times higher with FOLFIRINOX ($116,087 vs $49,007), primarily due to higher rates of adverse effects. The FOLFIRINOX regimen, however, demonstrated a significantly higher PFS compared with nab-paclitaxel + GEM (hazard ratio [HR], 40.68; 95% CI, 40.51-0.91). The nab-paclitaxel + GEM combination also demonstrated superior incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR), leading the authors to conclude greater economic value for nab-paclitaxel + GEM.16

However, a Markov model based on published clinical trials simulated the total costs and health outcomes of the 2 regimens, including direct medical costs of treatment, management of treatment-related costs, and provision of supportive care. It also found no significant difference in OS between the 2 regimens. The Table17 shows the ICER and ICUR of the 2 regimens compared with each other and with GEM monotherapy.17 Another economic analysis comparing the costs of FOLFIRINOX to nab-paclitaxel + GEM in a large insured US population found similar healthcare costs ($17,394 and $17,737) for first-line treatment in patients with metastatic pancreatic cancer, but higher supportive care costs, including antiemetics, hydration, and granulocyte colony-stimulating factor, for FOLFIRINOX.18

A 3-stage Markov analysis (PFS, progressed disease, and death) found that FOLFIRINOX was the most expensive regimen at an annual cost of $83,835, followed by nab-paclitaxel + GEM at $54,842. However, both yielded the highest nominal gains in life-years and QOL years compared with GEM monotherapy or GEM combined with cisplatin, oxaliplatin, or capecitabine.19 An analysis of survival gains in patients with metastatic pancreatic cancer after the introduction of GEM, FOLFIRINOX, and nab-paclitaxel + GEM found that the cumulative value of survival gains attributable to GEM and nab-paclitaxel + GEM would exceed the cost of therapy by up to $47.6 billion and $39 billion, respectively, for patients with metastatic pancreatic cancer diagnosed in 2015 or later, whereas the lifetime value of survival gains in patients who can tolerate the FOLFIRINOX regimen would reach up to $26.3 billion.20

Targeted Therapies and Immunotherapies

Immunotherapy has not yet proven to be beneficial in pancreatic cancer. A unique tumor microenvironment, low levels of tumor-infiltrating T lymphocytes, and lower levels of antigens to target allow pancreatic cancer to be resistant to immunotherapy. Studies to date with single-agent immunotherapy have not been successful; however, there are multiple clinical trials examining different combinations of immunotherapy agents. Thus, the potential exists for immunotherapy in some form to play a role in pancreatic cancer.21

The FDA approved pembrolizumab in 2017 for patients with advanced solid tumors that have microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) markers that have progressed following prior treatment and have no satisfactory alternative treatment options.22,23 Although this represents a small fraction of patients with pancreatic cancer, the potential exists for immunotherapy to play a role in pancreatic cancer.24 To date, there are no published studies on the cost-effectiveness of immunotherapy in the pancreatic cancer setting.

The only targeted agent shown to be effective in the small number of EGFR-positive tumors is erlotinib, and, even though there was a survival advantage when erlotinib was combined with GEM, the benefit was actually small, suggesting a subset of patient benefit.25 One study evaluated the budget impact of adding erlotinib to GEM for the treatment of locally advanced, nonresectable, or metastatic pancreatic cancer in a hypothetical model of 43 newly diagnosed patients in a 500,000-member managed care plan. The model estimated that 56% of the patients would be treated with GEM alone and 40% with combination therapy for 15.7 weeks per patient. The expected 1-year cost of $466,700 in the combination group was compared with $346,700 in the GEM-only group (2006 USD) translated to $0.020 PMPM.26

Cost-Containment Approaches for Managed Care

 
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