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Treatment For Lung Cancer
Treating lung cancer used to be simpler — because there simply were not as many treatments available. Today, people facing this disease have more options, and significantly higher survival rates, than they did even a few years ago.
Recent advances allow us to precisely tailor your treatment based on the particular features of your cancer. Newer options mean increased complexity, which is why it's essential to receive care from physicians who specialize in this disease.
At Fred Hutchinson Cancer Center, we have been personalizing lung cancer care for decades. Our experts offer comprehensive care — from prevention, screening and diagnosis to treatment and surveillance.
A diagnosis of cancer can feel overwhelming. We have an experienced, compassionate team ready to help.
Dr. Michael Mulligan discusses lung cancer treatment at Fred Hutch.
Lung Cancer Expertise at Fred Hutch Treatment TypesTreatment looks different for different people depending on your diagnosis. We tailor your treatment plan to you. Learn more about the treatment types offered at Fred Hutch.
ChemotherapyDepending on the type and stage of your cancer, your medical oncologist may recommend chemotherapy:
Lung cancer chemotherapy is generally given every three to four weeks in cycles, either in pill form or through an intravenous (IV) line in the hand or arm or a port in the chest.
Your Fred Hutch team will talk with you about the specific medicines we recommend for you, how you'll receive them, your treatment schedule and what to expect. We'll also explain how to take the best possible care of yourself during treatment and after, and we'll connect you with medical and support resources throughout Fred Hutch.
ImmunotherapyOne of the major changes in lung cancer treatment recently is the introduction of immunotherapies. These medicines harness your immune system to fight your cancer. They may be used alone or with chemotherapy or, in clinical trials, with other treatments.
Most lung cancer immunotherapy relies on medicines called checkpoint inhibitors. Fred Hutch physicians and researchers are exploring additional types of immunotherapy for lung cancer.
Learn more about Immunotherapy
Proton TherapyProton therapy is a form of radiation therapy that, for some lung cancer patients, allows for greater sparing of their organs from the effects of radiation exposure.
Proton Therapy Offers:
Too much radiation to the healthy tissue surrounding the tumor can increase the risk of side effects. This is a major concern when it comes to radiation treatment for lung cancer because the cancer may be close to your heart, healthy lung and other critical organs. The unique properties of protons allow proton radiation to better conform to your cancer, reducing excess radiation to the healthy tissues and organs around it.
A large clinical trial in lung cancer treatment recently showed that a patient's survival after lung cancer treatment is closely related to the amount of radiation the patient's heart received, and the amount of esophagus toxicity (swallowing difficulty) patients developed during radiation treatment (trial RTOG 0617). Proton therapy can decrease the radiation dose to the heart and the esophagus, as well as normal lung.
Types of Lung and Thoracic Cancers Treated With Proton TherapyBelow is a list of lung and thoracic cancers that can benefit from proton therapy. Our radiation oncologists use other forms of radiation to treat cancers, so they will provide you with an expert recommendation for your consideration.
You should consider proton therapy if you have lung cancer that has not spread outside your chest, especially along with one of the following:
Learn more about Proton Therapy
Radiation TreatmentMany people with lung cancer have radiation therapy alone or along with other treatments. It is painless and noninvasive, and each treatment lasts only minutes.
Radiation therapy may be used:
Different types of radiation treatments are used for different situations. A few examples of the types used for lung cancer are:
Fred Hutch patients have surgery at UW Medical Center - Montlake with thoracic surgeons who are among the best in the country. Surgeons at UW Medical Center do more lung operations than anywhere else in the Pacific Northwest. They also help diagnose and stage lung cancer and relieve symptoms of advanced disease.
Our surgeons have some of the most extensive experience in the world taking on the most complex cases, including patients who might be told elsewhere that they cannot have surgery or surgery is too risky.
Any surgery your team recommends will depend on the type and stage of your disease, your general health and your lung function. Your surgeon will probably remove lymph nodes too to check them for signs of cancer.
Targeted TherapyTargeted therapies are newer cancer treatments that work more selectively than standard chemotherapy. These medicines are used most often in people with advanced and recurrent lung cancer and are effective in patients with specific changes in their tumor genes.
The current standard of care is to test for changes in the genes EGFR, ALK, ROS1 and BRAF, which we can do using UW-OncoPlex, a diagnostic tool developed by researchers at UW Medicine. Treatments are being developed to target other genetic changes as well.
For lung cancer, targeted therapies called small molecules are used to block specific growth-factor receptors involved in cancer cell proliferation (growth and division of cancer cells). Examples include erlotinib (Tarceva), gefitinib (Iressa), crizotinib (Xalkori), alectinib (Alecensa) and others.
At Fred Hutch, patients have access to newer targeted therapies in clinical studies that aren't available otherwise. This is a very active area of research.
Stage 4 Neuroendocrine Small Cell Lung Cancer
Neuroendocrine small cell lung cancer (SCLC) occurs when neuroendocrine tumors develop as a result of overactive, cancerous neuroendocrine cells. Stage 4 is extensive stage SCLC.
Neuroendocrine cells are specialized cells found in many parts of the body, including the gastrointestinal (GI) tract, gallbladder, and lungs.
These cells receive signals from the brain to produce and release certain hormones that control many bodily functions.
Neuroendocrine tumors (NETs) develop when neuroendocrine cells become overactive and cancerous. NETs typically involve the GI tract and the lungs.
Small cell lung cancer (SCLC), also called oat cell cancer, accounts for 10–15% of all lung cancers. It is also the most prevalent type of neuroendocrine lung tumor.
Once a doctor makes a diagnosis, they determine how much the cancer has spread through staging.
Most doctors use a two-stage system for SCLC, dividing it into limited and extensive disease. Generally, extensive disease is the same as stage 4.
Stage 4 cancer means that cancer cells have spread from an original tumor to other parts of the body.
TNM stagingSome doctors may use the TNM staging system, though this is uncommon. TNM stands for tumor, node, and metastasis.
Stage 4, also called the advanced stage, means that cancer has spread. At stage 4, the tumor can be any size and may or may not have spread to nearby lymph nodes.
Neuroendocrine lung tumors are a family of tumors that arise from the cells that line the bronchi and other parts of the lung.
This disease group has distinct clinical and pathological characteristics. It varies in cell structure, features, appearance, presence of dead cells (necrosis), and the number of dividing cells (mitotic index).
Typical carcinoid (TC)TCs are low grade, slow-growing tumors that rarely spread (metastasize) outside the lungs. This type of tumor has a good outlook. Management and treatment typically involve surgery. Smoking is not associated with TCs.
Atypical carcinoid (AC)ACs are intermediate grade tumors that commonly affect people who smoke. They grow faster and tend to spread to the bones and liver.
SCLCSCLC is the most common NET of the lungs. It is also the most aggressive. In 70% of people with SCLC, the cancer has already spread to other areas by the time they receive a diagnosis. Smoking is the most significant risk factor for developing SCLC.
Large cell neuroendocrine carcinoma (LCNEC)Similar to SCLC, LCNEC is also a fast-growing tumor. However, it is not as common as SCLC. Smoking is also a major risk factor for developing LCNEC. LCNECs have cancerous cells that look similar to SCLC, though they are larger.
A 2021 article in the Annals of Oncology explains that people with carcinoids have a better outlook compared with those with SCLC and LCNEC. People who have carcinoids are also generally younger, and the disease is not strongly associated with smoking.
The 5-year relative survival rate for people with SCLC is 7%, compared with a 25% survival rate for those with non-small cell lung cancer.
Most people receive an SCLC diagnosis when their cancer has already spread extensively. A 2020 review notes that while SCLC tends to initially respond to chemotherapy, it is likely that people with it will go on to experience relapse or the disease will progress.
A person with SCLC may have symptoms related to a localized lesion (in the lung or lungs) or distant metastases (cancer that has spread to other parts of the body). Symptoms of localized lesions typically involve airway obstruction. This is because the cancer is in one or both lungs, meaning it will affect a person's airway.
Symptoms may include:
As the disease progresses and spreads, people may experience other symptoms, such as:
SCLC may also cause:
Endocrine involvement may include:
The majority of people with SCLC contact to their doctor because they experience symptoms of the disease. Before doctors ask people to undergo tests, they will first perform a thorough physical exam and take a medical history.
BiopsyIf results suggest the possibility of lung cancer, doctors may ask a person to undergo several tests. To make a diagnosis, specialists extract lung cell samples and examine them in a lab.
These tests include:
A pathologist will evaluate the samples and examine them under a microscope to check for the cell structure and appearance unique to SCLC.
Imaging techniquesDoctors can use several imaging techniques to help diagnose and monitor SCLC and other lung cancers. These include chest X-rays, CT scans, MRIs, bone scans, and PET scans.
The imaging techniques help identify suspicious masses or tumors that may be cancerous. They also help monitor cancer spread, its response to treatment, relapse, and whether it has returned.
Treatment for SCLC depends on the cancer's aggressiveness and a person's health status.
People with limited stage SCLC typically receive a combination of chemotherapy and chest radiation therapy. Surgery may also be an option for otherwise well individuals if the tumor is limited to one area. A person also receives chemotherapy after surgery.
Since brain metastasis is common, many people also receive radiation therapy to the head, called prophylactic cranial irradiation.
Surgery and radiation are not useful as initial treatments for extensive stage SCLC. The standard of care for this condition is radiation and a combination of the chemotherapy drugs etoposide and either cisplatin or carboplatin.
A 2020 review mentions that immunotherapy combined with chemotherapy is the new frontline treatment for SCLC. This combination may significantly improve the overall outlook for people with extensive stage SCLC.
Radiation therapy can also relieve symptoms caused by cancer growth in the lungs or when cancer has spread to other areas. People with additional health problems may benefit from low chemotherapy doses or supportive care to address complications and keep them as comfortable as possible.
Stage 4 neuroendocrine SCLC is the most common NET of the lung. Doctors often diagnose it when it has already spread.
Compared with other lung cancers, it has a poorer outlook. It is likely that a person will experience relapse even after their condition responds well to initial treatments.
Better Together? Costs Of First-line Chemoimmunotherapy For Advanced Non–Small Cell Lung Cancer
Compared with first-line immunotherapy or chemotherapy alone, combination chemoimmunotherapy for advanced/metastatic non–small cell lung cancer has significantly higher antineoplastic drug and associated medical costs.
ABSTRACT
Objectives: Recent advances have created options for first-line (1L) treatment of advanced/metastatic non–small cell lung cancer (aNSCLC). The study objectives were to describe the utilization of 3 classes of 1L treatment—chemotherapy (CT), immunotherapy (IO), and chemoimmunotherapy (IO+CT)—and the total, third-party payer, direct health care costs.
Study Design: Retrospective, administrative claims database analysis of patients with aNSCLC who initiated 1L treatment between January 1, 2017, and May 31, 2019, with IO, CT, or IO+CT.
Methods: Microcosting enumerated health care resource utilization, including antineoplastic drug costs, using standardized costs. Generalized linear models estimated per-patient per-month (PPPM) costs during 1L treatment, and adjusted cost differences in 1L among treatment cohorts were calculated using recycled predictions.
Results: A total of 1317 IO-, 5315 CT-, and 1522 IO+CT-treated patients were identified. Utilization of CT declined from 72.3% to 47.6% between 2017 and 2019, replaced by use of IO+CT, which increased from 1.8% to 29.8%. Total PPPM costs in 1L were highest with IO+CT at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT vs IO cohort (P < .001) and IO costs were $1024 (95% CI, $67-$1980) lower than CT (P = .04).
Conclusions: IO+CT accounts for almost one-third of 1L aNSCLC treatment modalities, coinciding with a reduction in treatment with CT. Costs for patients treated with IO were lower than those for patients treated with both IO+CT and CT alone, driven primarily by antineoplastic drug and associated medical costs.
Am J Manag Care. 2023;29(5):e129-e135. Https://doi.Org/10.37765/ajmc.2023.89360
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Takeaway Points
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Lung cancer is the second most common cancer and the leading cause of cancer death for men and women in the United States.1,2 In 2018, deaths from lung cancer nearly outnumbered those from breast, prostate, colorectal, and brain cancers combined.3 In 2021, more than 235,000 Americans received lung cancer diagnoses and 131,880 died from the disease.2
Although reductions in smoking, along with diagnostic and therapeutic advances, have resulted in a recent decline of lung cancer mortality rates of 5%, the 5-year survival rate among patients with newly diagnosed disease remains around 20%.2 In 2015, the approval of the first immunotherapy (IO) drug, nivolumab, ushered in a new era of treatment for advanced non–small cell lung cancer (aNSCLC) with its indication as a second-line treatment.3 This approval was shortly followed by the approval of pembrolizumab, which in October 2016 became the first IO agent approved in the first-line (1L) therapeutic setting for patients with a PD-L1 expression level of 50% or more.4 Less than a year later in May 2017, the chemoimmunotherapy (IO+CT) regimen of pembrolizumab plus chemotherapy (CT) was approved for the 1L setting regardless of PD-L1 expression level.5 Today, the landscape continues to evolve, including novel approved IO agents and combination IO therapies with and without a CT component.6,7 In May 2020, nivolumab plus ipilimumab became the first combination IO+IO treatment approved for aNSCLC.8
The US health care system has historically imposed no restrictions on the reimbursement of cancer therapies based on cost-effectiveness. However, growing attention is being paid to treatment costs as a result of value-based care (VBC) initiatives such as the Oncology Care Model (OCM) and its replacement initiative, the Enhanced Oncology Model (EOM), which impose shared financial risk between providers and payers.9 Moreover, the rapid expansion of high-cost, novel agents such as IO into the 1L setting for aNSCLC raises concerns about affordability, especially given the trend toward combination therapy. Drug price is typically the most important factor in sensitivity analyses of cost-effectiveness, yet other aspects of care such as office visits, infused drug administration, supportive care agents, and emergency and hospital care for adverse events (AEs) may contribute substantially to the economic burden of particular therapies.
Few studies have examined the differences in health care resource utilization (HCRU) or the total costs to third-party payers since the introduction of combination pembrolizumab plus CT in 2017.10 It was our intent to focus on the cost impact of treatment preference for the vast majority of patients, in whom a driver mutation is not identified and for whom clinical practice guidelines support the use of varied therapeutic approaches. As such, drugs targeting the major genetic pathways involved (eg, EGFR, ALK, ROS1) were excluded from this study. Additionally, combination IO+IO therapies were excluded because the FDA approval was outside the designated study period, making any observed use off-label or within the context of a clinical trial. Therefore, the objectives of this study were to describe the treatment patterns, HCRU, and costs associated with adoption of 1L IO and IO+CT regimens since January 2017. We compared the adjusted differences in total all-cause costs during 1L therapy for patients treated with IO+CT vs IO monotherapy vs CT alone.
METHODS
Data Source
Medical and pharmacy claims from the Ability Patient Complete (APC) database were used to identify US patients 18 years or older who received aNSCLC diagnoses and initiated 1L systemic therapy with IO monotherapy, CT alone, or IO+CT agents between January 1, 2017, and May 31, 2019. The APC database is nationally representative, including claims during the past 5 years on 160 million covered patients from more than 150 payers across all states representing commercial health plan (~50%), Medicaid (~40%), and Medicare Advantage/supplemental sources. Claims-based selection criteria are described in Figure 1. Patients were required to have had a lung cancer diagnosis, have received a diagnosis of advanced/metastatic disease, and have initiated 1L systemic therapy with any IO monotherapy, CT alone, IO+CT, or targeted regimen approved for treatment of aNSCLC on or after January 1, 2017. Although patients who received a targeted treatment (eg, VEGF inhibitor, monoclonal antibody) were initially selected, only the frequency of use over time was reported for these agents, and this study did not specify HCRU or cost-of-care analyses for them. Patients were identified as having aNSCLC if any claim included a diagnosis code for a distant lymph node or distant metastatic site. The database included the patients' full claims history through May 30, 2019.
Line of Therapy and Study Cohorts
Line of therapy (LOT) assignment was made by grouping agents that were administered within 30 days of each other. Use of a new or additional agent, discontinuation of an agent for at least 120 days, or a gap in the administration of an agent for more than 120 days formed a new LOT. Maintenance therapy was defined as the continuation of an IO agent (eg, pembrolizumab) following combination IO+CT, provided that the last claim for CT occurred within 120 days of the next claim for the IO agent. As such, maintenance therapy was not considered a new LOT, but a continuation of 1L therapy. Following LOT assignment, patients were categorized into 4 mutually exclusive cohorts based on the 1L treatment regimen received: (1) IO monotherapy, (2) IO+CT, (3) CT only, and (4) all other regimens (including targeted therapy).
HCRU and Costs
The study objectives were to estimate and compare the total costs of care during 1L therapy for patients by treatment cohort. Only patients treated with IO monotherapy, IO+CT, or CT alone were included in this portion of the analysis, as it was assumed that many patients treated with other regimens likely had ALK or EGFR mutations, and therefore their disease was not comparable with that of patients treated with IO or CT. For the 3 cohorts of interest, HCRU was first estimated per 1L therapy cohort based on the Current Procedural Terminology codes listed in the claims, which indicated the site of care where services were rendered. First, all hospital stays were identified, followed by emergency department (ED) visits, and the remainder of care was assigned to the outpatient/office setting. Next, a microcosting approach was taken to enumerate the per-patient costs of each medical or pharmaceutical service or product rendered in each setting during 1L therapy. Standardized unit costs from CMS fee schedules for medical services and average wholesale price (AWP) for pharmaceutical agents, including antineoplastics, were applied to each service.11-13 Because units (ie, dose administered in mg/kg) were not uniformly available from the claims for IO therapies and other infused drugs, a standard dosage was applied to each antineoplastic drug claim (ie, mg/kg or mg/m2 per schedule of administration using the average weight/height of US men/women). The cost was calculated as the standard dosage multiplied by the AWP. All costs were adjusted to an average of the Consumer Price Index for the United States in 2020.
Statistical Analysis
Patient demographics and clinical characteristics were estimated in each cohort using descriptive statistical techniques including mean, SD, and median for continuous variables and counts and proportions for categorical variables. Statistical comparisons of demographics and clinical characteristics were not made among the cohorts, as it was not an objective of this research. Due to the potential variability in follow-up time (no minimum was required), exposure-adjusted estimates of HCRU and costs in the 1L setting were calculated as per-patient per-month (PPPM). For HCRU and costs, the numbers of events (eg, inpatient admissions) or total dollars were divided by the total days of therapy and then multiplied by 30. Given that a cycle of systemic therapy (IO or CT) is 1 infusion every 2, 3, or 4 weeks, the total days of therapy value for patients with less than 1 month of follow-up was extrapolated to 30 in order to not artificially inflate PPPM estimates in cases where a patient had only 1 claim for systemic therapy.
Using the PPPM approach, 2 estimates of costs were calculated: (1) mean unadjusted PPPM, and (2) mean adjusted difference in costs among the 3 cohorts. First, the adjusted PPPM costs were estimated using a generalized linear model (GLM) with γ distribution and log-link function based on goodness-of-fit testing adjusted for sex, age at 1L initiation, insurance payer type, US geographical region, time from first diagnosis to 1L initiation, and Charlson Comorbidity Index (CCI) score. Next, the incremental adjusted mean differences in PPPM total health care costs and the respective individual component costs (eg, inpatient hospitalization, ED visit, office visit, and pharmacy) among the cohorts were calculated (ie, IO monotherapy vs IO+CT, IO monotherapy vs CT, and IO+CT vs CT) using the recycled predictions method.14 Briefly, it isolates the effect of the treatment class on the outcome by holding constant the values for all other covariates, which in this case were sex, age at 1L therapy initiation, payer, US region of residence, and CCI score. To obtain the mean values for the covariates, a probabilistic sampling technique was repeated 100 times in the patient population and a GLM was used to predict the PPPM costs. Next, the mean estimates were used as covariate parameters to calculate the incremental cost differences among the cohorts.
RESULTS
Overall, 125,269 individuals were initially selected and 9062 (7.2%) met the study inclusion/exclusion criteria (Figure 1). The 1L therapy distribution of patients during the entire period was 14.5% receiving IO (n = 1317), 16.8% receiving IO+CT (n = 1522), 58.7% receiving CT (n = 5315), and 10.0% receiving other therapies (n = 908). The proportion of patients receiving CT declined from 72.3% in January through May 2017 to 47.6% during the corresponding months of 2019 (Figure 2). Use of IO+CT increased from 1.8% to 29.8% over the same interval, whereas use of IO therapies declined from 16.4% to 12.0% and use of other 1L therapies increased from 9.5% to 10.7%.
Patient characteristics were similar among those who received IO, IO+CT, and CT in 1L (Table 1). A slightly higher proportion of patients treated with IO+CT were male (54.7% vs 51.5% for IO and 50.9% for CT), whereas patients receiving IO were slightly older (median, 64 years) compared with those receiving IO+CT (62 years), and CT (63 years). Patients who received IO+CT had a lower CCI score (mean of 1.8) compared with those who received IO or CT (mean of 2.1 for each).
The mean (SD) duration of 1L treatment (Table 1) was longest for IO-treated patients at 6.5 (7.3) months compared with IO+CT-treated patients at 5.6 (5.1) months and CT-treated patients at 3.0 (1.6) months. Treatment duration did vary according to the time of initiation (as follow-up time varied) but did so consistently across cohorts. Mean PPPM inpatient hospital admission and ED visit rates during 1L therapy were similar across the cohorts, at 0.23 and 0.34, respectively, for IO-treated patients, 0.24 and 0.37 for IO+CT–treated patients, and 0.23 and 0.35 for CT-treated patients. Mean PPPM outpatient physician office visits were 2.1 for the IO cohort, 2.5 for the IO+CT cohort, and 2.6 for the CT cohort (Table 1).
The mean unadjusted total health care PPPM costs during 1L therapy are shown in Figure 3 (including estimates for medical, pharmacy, and antineoplastic drug costs). The highest PPPM costs during 1L therapy were in the IO+CT cohort at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Mean PPPM antineoplastic drug costs were highest in the IO+CT cohort at $20,234, compared with $2040 in the CT cohort and $12,116 in the IO cohort. Associated medical costs (eg, office visits, hospitalizations, supportive care) were highest in the CT cohort at $13,178 and lowest in the IO cohort at $2743.
Cost differences comparing each cohort are shown in Table 2. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT cohort vs the IO cohort (P < .0001). Further, PPPM medical costs were $5876 higher and antineoplastic drug costs were $7596 higher. Compared with CT costs, IO costs were $1024 lower (95% CI, $67-$1980) (P = .04), driven by substantially ($10,265) lower medical costs notwithstanding substantially ($10,025) higher antineoplastic drug costs for IO. As such, total health care PPPM costs in the IO+CT cohort were also higher by $13,131 (95% CI, $11,286-$14,437) compared with those in the CT cohort.
DISCUSSION
The last 5 years have seen expansive growth in the approved indications for IO in aNSCLC, which has led to meaningful improvements in clinical outcomes for patients. However, these improvements impose a cost on health care payers, patients, and society through government-subsidized health care plans. Research has demonstrated that at locally relevant willingness-to-pay thresholds, IO agents are cost-effective.10 Studies comparing IO+CT regimens with CT alone have reported similar findings and conclusions (albeit at varying levels of willingness-to-pay thresholds and quality-adjusted life-years),4,15,16 but as far as we are aware, this research represents the first nationally representative real-world data study to estimate and compare the direct total health care costs to payers among IO, CT, and IO+CT regimens for 1L treatment of aNSCLC since the approval of IO in the 1L therapeutic setting.
We observed the direct impact of the introduction of IO therapy by first assessing its rate of adoption. Although the use of IO monotherapy in the 1L setting has remained relatively constant, the use of IO+CT has increased at a rate of more than 5% every 6 months between 2018 and 2019. Our data mirror the timing of the August 2018 approval of pembrolizumab plus CT for 1L treatment of aNSCLC, with a near doubling of the proportion of patients initiating 1L IO+CT between the first and second half of 2018 (99% of patients in the study sample had received pembrolizumab-containing regimens).4 The observation that IO monotherapy use remained relatively constant may be explained by its preferred use in patients with high PD-L1 expression (although PD-L1 data were not available for analysis in this study), cost concerns for combination therapy (especially among providers participating in VBC initiatives such as OCM), and/or the inability of certain patients to tolerate CT. Consequently, IO monotherapy remains a relevant treatment approach for appropriate patients with aNSCLC (eg, those with ≥ 50% PD-L1 expression).
Next, we found that IO+CT–treated patients had the highest total PPPM health care costs in the 1L setting, which were significantly higher than those of patients treated with IO or CT. These findings were not explained by HCRU differences, as no statistically significant differences in hospitalizations or ED visits were found among the 3 cohorts. Instead, higher antineoplastic drug costs likely explain a large proportion of this difference, a phenomenon that has previously been reported with novel aNSCLC agents such as osimertinib, which was adopted into routine clinical practice and led to a 100% increase in total health care costs.17 In addition, a possible explanation for the greater antineoplastic drug costs for the IO+CT cohort compared with IO monotherapy or CT alone may be driven by the use of pemetrexed, which remains unavailable in generic formulation in the United States. In the IO+CT cohort, more than 80% of individuals received pembrolizumab in combination with pemetrexed, compared with less than 25% of patients in the CT cohort. In addition to the higher drug costs of pembrolizumab and pemetrexed, substantially ($8860) higher PPPM medical costs for IO+CT were observed compared with the total PPPM medical costs for IO of $2743. The difference may result at least in part from the association of CT with costs for the management of AEs, which may require supportive care interventions. The declining duration of 1L therapy over time in all cohorts may have been associated with fewer patients in each category over time, shortened length of follow-up, or switches to different types of therapy if the current therapy was not efficacious as time continued.
Finally, we observed significantly higher medical costs for patients who received CT alone vs either IO or IO+CT. Further research is warranted to examine whether higher medical costs of CT alone may be related to inferior clinical outcomes for patients or whether these differences could be explained by systematic clinical differences among the cohorts. Patients in the end-of-life phase of cancer care, during which treatment with CT alone may be more frequent, incur direct medical costs substantially higher than those of patients in the continuing phase of treatment.18
Limitations
There are several limitations to the current study specifically and inherent to administrative claims–based analyses. First, HCRU and total PPPM cost estimates may be prone to error due to lack of complete follow-up. Second, paid costs were not available, and drug reimbursement rates may vary by payer. Third, LOT assignment was based on an algorithm, and as such may be subject to misclassification. Strengths of this study include the large sample size and the representation of Medicaid patients in the APC database, which is higher than in other commercial claims-based databases.
CONCLUSIONS
IO+CT in the 1L therapeutic setting now accounts for nearly a third of 1L aNSCLC treatment modalities, a shift that has coincided with a 25% reduction in the proportion of patients treated with 1L CT from 2017 to 2019. Additionally, the use of IO monotherapy has remained relatively constant at 12% to 16% during this interval. Patients treated with IO monotherapy had fewer outpatient visits PPPM, but no differences in hospital admissions or ED visits were observed among the 1L therapy cohorts. Further, CT-containing regimens were associated with higher nonantineoplastic health care costs than were IO monotherapy regimens. The transition to a VBC framework and shared financial risk payment models such as OCM warrants continued analyses of cost-effectiveness to provide patients, providers, payers, and policymakers the data needed to inform the design of benefit plans, shared decision-making, and optimized health care outcomes, both clinically and financially. Further research will help to stratify cost-effectiveness of the increasingly myriad therapeutic options for aNSCLC, which include CT, IO, and targeted therapies alone and in combination.
Acknowledgments
The authors would like to acknowledge Alexandrina Balanean and Danielle Gentile of Cardinal Health for manuscript editing.
Author Affiliations: Cardinal Health (JK, DL, DC, BF), Dublin, OH; Bristol Myers Squibb (JH, SJL), Lawrenceville, NJ.
Source of Funding: This research was sponsored by Bristol Myers Squibb.
Author Disclosures: Dr Kish reports former employment and stock ownership in Cardinal Health. Mr Liassou reports employment at Cardinal Health. Dr Hartman reports employment and stock ownership in Bristol Myers Squibb, which is the manufacturer and patent owner of a competitor regimen. Dr Lubinga reports employment and stock ownership in Bristol Myers Squibb. Mr Chopra reports employment at Cardinal Health. Dr Feinberg reports employment and stock ownership in Cardinal Health.
Authorship Information: Concept and design (JK, JDH, SJL, DC, BF); acquisition of data (JK, DC); analysis and interpretation of data (JK, DL, JDH, SJL, DC, BF); drafting of the manuscript (JK, BF); critical revision of the manuscript for important intellectual content (JK, DL, JDH, SJL, BF); statistical analysis (JK, DL); obtaining funding (JDH); administrative, technical, or logistic support (SJL); and supervision (JK, JDH).
Address Correspondence to: Bruce Feinberg, DO, Cardinal Health, 7000 Cardinal Pl, Dublin, OH 43017. Email: bruce.Feinberg@cardinalhealth.Com.
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