Cost-minimization analysis of panitumumab compared with cetuximab for first-line treatment of patients with wild-type RAS metastatic colorectal cancer

Abstract

Objective:

To compare the costs of first-line treatment with panitumumab + FOLFOX in comparison to cetuximab + FOLFIRI among patients with wild-type (WT) RAS metastatic colorectal cancer (mCRC) in the US.

Methods:

A cost-minimization model was developed assuming similar treatment efficacy between both regimens. The model estimated the costs associated with drug acquisition, treatment administration frequency (every 2 weeks for panitumumab, weekly for cetuximab), and incidence of infusion reactions. Average anti-EGFR doses were calculated from the ASPECCT clinical trial, and average doses of chemotherapy regimens were based on product labels. Using the medical component of the consumer price index, adverse event costs were inflated to 2014 US dollars, and all other costs were reported in 2014 US dollars. The time horizon for the model was based on average first-line progression-free survival of a WT RAS patient, estimated from parametric survival analyses of PRIME clinical trial data.

Results:

Relative to cetuximab + FOLFIRI in the first-line treatment of WT RAS mCRC, the cost-minimization model demonstrated lower projected drug acquisition, administration, and adverse event costs for patients who received panitumumab + FOLFOX. The overall cost per patient for first-line treatment was $179,219 for panitumumab + FOLFOX vs $202,344 for cetuximab + FOLFIRI, resulting in a per-patient saving of $23,125 (11.4%) in favor of panitumumab + FOLFOX.

Conclusions:

From a value perspective, the cost-minimization model supports panitumumab + FOLFOX instead of cetuximab + FOLFIRI as the preferred first-line treatment of WT RAS mCRC patients requiring systemic therapy.

Keywords::

• Cost-minimization – Panitumumab – Cetuximab – FOLFOX – FOLFIRI – Colorectal cancer – First-line

Introduction

Overview of mCRC

In the US, colorectal cancer is the third most common cancer in both men and women, and the second leading cause of cancer death1. Incidence rates have been decreasing for most of the past 2 decades; however, an estimated 93,090 cases of colon cancer and 39,610 cases of rectal cancer are expected to be diagnosed in 20152. Patients with metastatic colorectal cancer (mCRC) experience significant morbidity and diminished quality-of-life. The 5-year relative survival rate is estimated to be less than 13% in patients with mCRC in the US, indicating a continued need to improve treatment outcomes1. Surgical resection of the liver is curative in only a very small proportion of patients; therefore, the goal of treatment for most patients with mCRC is to prolong survival for as long as possible while maintaining quality-of-life.

Current treatments and RAS status

According to the National Comprehensive Cancer Network (NCCN) guidelines for the first-line treatment of patients with mCRC, recommended chemotherapy regimens include FOLFIRI (5-fluorouracil + leucovorin + irinotecan), FOLFOX (5-fluorouracil + leucovorin + oxaliplatin), CapeOX (capecitabine + oxaliplatin), 5-FU/LV (5-fluorouracil + leucovorin) or capecitabine, or FOLFOXIRI (5-fluorouracil + leucovorin + oxaliplatin + irinotecan). In selected patients with mCRC, some of these chemotherapy regimens can be combined with epidermal growth factor receptor (EGFR) inhibitors, such as panitumumab or cetuximab, or the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, as part of first-line treatment3^,4.

EGFR-targeted therapies have been shown to be ineffective in tumors expressing mutations in KRAS exons 25–9. Identification of additional RAS mutations beyond KRAS exon 2 (i.e., mutations in KRAS exons 3 and 4 and NRAS exons 2, 3, and 4) predicts a lack of response to panitumumab10^,11 and cetuximab12–14 in combination with oxaliplatin-based chemotherapy. Therefore, patients with known RAS (KRAS and NRAS) mutations should not be treated with an anti-EGFR agent3^,4.

RAS genetic testing has indicated that ∼50% of patients with mCRC have RAS mutations10. Identification of RAS mutation status may reduce mCRC treatment costs by allowing physicians to target patients who are likely to benefit from treatment with EGFR inhibitors and to minimize the number of patients receiving anti-EGFR agents who are unlikely to respond favorably.

Head-to-head clinical trials

Several clinical trials have been conducted to compare targeted biologic treatments in patients with mCRC. ASPECCT was a head-to-head study comparing panitumumab to cetuximab in chemorefractory patients. This phase 3, open-label, randomized, non-inferiority, multi-center clinical study was designed to compare the efficacy and safety of treatment with panitumumab (n = 499) and with cetuximab (n = 500) in patients previously treated wild-type (WT) KRAS mCRC. The estimated median progression-free survival (PFS) was 4.1 months (95% confidence interval [CI] = 3.2–4.8) in the panitumumab arm and 4.4 months (95% CI = 3.2–4.8) in the cetuximab arm. The estimated median overall survival (OS) was 10.4 months (95% CI = 9.4–11.6) in the panitumumab arm and 10.0 months (95% CI = 9.3–11.0) in the cetuximab arm15. These findings demonstrate that panitumumab is non-inferior to cetuximab and that both agents provide similar OS benefit in this population. Although the ASPECCT trial was not conducted in a first-line setting, it is the only head-to-head trial that has compared cetuximab with panitumumab.

Model overview

To our knowledge, the economic value of panitumumab relative to cetuximab has not been assessed in patients with WT RAS mCRC. Assuming similar first-line efficacy between panitumumab and cetuximab based on the ASPECCT head-to-head study, we conducted a cost-minimization analysis comparing panitumumab + FOLFOX and cetuximab + FOLFIRI in the first-line treatment of patients with WT RAS mCRC with the aim to determine the least costly alternative. RAS PFS data from the first-line PRIME trial comparing panitumumab + FOLFOX vs FOLFOX alone was used. The respective chemotherapy backbones used in combination with panitumumab and cetuximab in the cost-minimization analysis were selected in accordance with approved prescribing information in the US16^,17. The analysis was performed from a third-party payer perspective in the US and compared the direct medical care costs of treatment with panitumumab (intravenous [IV] infusion: 6 mg/kg every 2 weeks until disease progression) + FOLFOX relative to cetuximab (IV infusion: loading dose of 400 mg/m² and weekly maintenance doses of 250 mg/m² until disease progression) + FOLFIRI in the first-line setting.

Patients and methods

Model population, WT RAS

The model population was assumed to be similar to the patient population that was included in the first-line PRIME clinical trial for panitumumab in the treatment of mCRC. This population was defined as adults (aged ≥18 years) with non-mutated WT RAS and a diagnosis of mCRC who had not undergone prior therapies, including chemotherapy, oxaliplatin, EGFR inhibitors, radiotherapy (≤14 days before randomization) or other investigational therapies (≤30 days before randomization). Additionally, enrolled patients had an Eastern Cooperative Oncology Group (ECOG) status of 0, 1 or 2 and at least one unidimensionally measurable lesion of at least 20 mm per modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.

Model structure

By definition, a cost-minimization model assumes that the treatments being compared have similar efficacy. The differences in costs between the treatments are estimated to determine the least costly treatment. In this case, we assumed equal PFS for panitumumab + FOLFOX and cetuximab + FOLFIRI, and we estimated the costs associated with drug acquisition, treatment administration frequency (every 2 weeks for panitumumab, weekly for cetuximab), and incidence of infusion reactions. A cost-minimization model was selected as an appropriate way to evaluate the cost of panitumumab + FOLFOX vs cetuximab + FOLFIRI in the first-line treatment of patients with WT RAS mCRC, because trial results from ASPECCT demonstrated similar efficacy for patients treated with panitumumab and cetuximab15. The time horizon of the model is that of average first-line PFS of a patient with WT RAS mCRC treated with an EGFR inhibitor. Figure 1 provides a graphical representation of how costs for each treatment are estimated in the model.

Figure 1. Model structure.

Survival estimation

PFS is used in combination with the administration schedule of each treatment and the percentage of doses administered to estimate the number of infusions for panitumumab + FOLFOX and cetuximab + FOLFIRI. In clinical trials of oncology treatments, PFS is often reported as the median PFS. The mean PFS is a better estimate of the expected duration of treatment, but is not directly calculable from clinical trial data due to censoring of patient data. To estimate the mean, parametric survival analysis can be used to extrapolate beyond the data collection period.

Using data from the first-line PRIME clinical trial, we conducted parametric survival analyses on the PFS of patients with WT RAS mCRC treated with panitumumab + FOLFOX. Three parametric models were tested, based on the intrinsic assumptions they make regarding changes to the hazard rate over time. Specifically, these were exponential (constant hazard rate), Weibull (hazard rate either increases or decreases [monotonic]) and log-logistic (hazard rate either increases and then decreases or vice versa [non-monotonic]).

The best-fit survival curve was the Weibull, which was selected as the base-case estimate of mean PFS. Best-fit was determined through the use of a statistical goodness-of-fit test (Akaike information criterion), overlay of the fitted curves on the PFS Kaplan-Meier plots, and graphical diagnostic tests18. Figure 2 displays the PFS Kaplan-Meier plot and the fitted Weibull curve for panitumumab + FOLFOX.

Figure 2. Panitumumab + FOLFOX (5-fluorouracil + leucovorin + oxaliplatin) progression-free survival Kaplan-Meier plot and fitted Weibull Curve.

Model inputs

Drug acquisition costs in the base-case analysis were modeled using Medicare average sales prices from the Payment Allowance Limits for Medicare Part B Drugs19. Wholesale acquisition costs from Red Book20 were examined in scenario analyses (not shown here). Product exposure was defined as the average dose delivered (every 2 weeks for panitumumab and weekly for cetuximab) and the percentage of doses administered. For direct treatment comparison, average anti-EGFR doses were calculated from the ASPECCT clinical trial, and average doses of chemotherapy regimens were based on product labels. Assuming similar values between panitumumab + FOLFOX and cetuximab + FOLFIRI, PRIME data were used to calculate the percentage of doses administered. Except for infusion reactions, the model assumed that all adverse events were similar between panitumumab and cetuximab and that the adverse event was managed by delaying or stopping mCRC treatment15. Table 1 presents all drug acquisition, administration, RAS mutation testing, and adverse event-related input values, sources, and assumptions considered by the model.

Table 1. Model input parameters.

Input parameter	Input value			Source
Progression-free survival				Mean of Weibull progression-free survival curve from parametric survival analysis of PRIME updated final data cut for patients with WT RAS; assumed cetuximab would have same PFS
Panitumumab + FOLFOX	69.27 weeks
Cetuximab + FOLFIRI	69.27 weeks
Patient characteristics	Mean (SD)
Weight (kg) (n = 5537)	81.59 (20.802)			Data from NHANES21. Due to small sample sizes of US patients in ASPECCT, we used the general population NHANES values for the base case
Body surface area (m^2) (n = 5525)	1.91 (0.249)
Drug acquisition costs: Average sales price	Dose		Payment limit
Panitumumab	10 mg		$91.231	HCPCS code J9303 from Payment Allowance Limits for Medicare Part B Drugs19
Cetuximab	10 mg		$52.520	HCPCS code J9055 from Payment Allowance Limits for Medicare Part B Drugs19
5-FU	500 mg		$2.123	HCPCS code J9190 from Payment Allowance Limits for Medicare Part B Drugs19
Irinotecan	20 mg		$4.539	HCPCS code J9206 from Payment Allowance Limits for Medicare Part B Drugs19
Oxaliplatin	0.5 mg		$0.269	HCPCS code J9263 from Payment Allowance Limits for Medicare Part B Drugs19
Leucovorin	50 mg		$4.308	HCPCS code J0640 from Payment Allowance Limits for Medicare Part B Drugs19
Drug acquisition costs: Wholesale acquisition cost	Vial strength	Vial size	Cost per vial
Panitumumab	20 mg/mL	5 mL	$926.50	WAC for NDC 55513-0954-01 from the Red Book20
Cetuximab	2 mg/mL	50 mL	$514.55	WAC for NDC 66733-0948-23 from the Red Book20
5-FU	50 mg/mL	10 mL	$2.75	WAC for NDC 10139-0063-11 from the Red Book20
Irinotecan	20 mg/mL	2 mL	$12.34	WAC for NDC 61703-0349-16 from the Red Book20
Oxaliplatin	5 mg/mL	10 mL	$86.63	WAC for NDC 61703-0363-18 from the Red Book20
Leucovorin	50 mg	–	$4.40	WAC for NDC 25021-0813-66 from the Red Book20
Average dose	Input value
Panitumumab	5.98 mg/kg			ASPECCT Clinical Study Report Table 14-05.002.001
Cetuximab
Loading dose	394.10 mg/m^2			ASPECCT Ad Hoc Analysis Table us-2.5.800.001
Maintenance doses	247.52 mg/m^2			ASPECCT Ad Hoc Analysis Table us-2.5.800.001
Oxaliplatin	85.00 mg/m^2			Recommended dose from oxaliplatin prescribing information22
Irinotecan	180.00 mg/m^2			Recommended dose from irinotecan prescribing information23
5-FU
Day 1	400.00 mg/m^2			Recommended dose from oxaliplatin prescribing information22
Day 2	600.00 mg/m^2			Recommended dose from oxaliplatin prescribing information22
Leucovorin
Day 1	200.00 mg/m^2			Recommended dose from leucovorin prescribing information24
Day 2	200.00 mg/m^2			Recommended dose from leucovorin prescribing information23
Percentage of doses administered^a	Input value
Panitumumab + FOLFOX	94.8%			PRIME trial data on file Assumed cetuximab would have same ratio
Cetuximab + FOLFIRI	94.8%
RAS testing	Input value
Percentage of patients tested before starting first-line treatment	0.0%			Assumed no patients had prior RAS testing in the base-case analysis
Cost of RAS genetic testing	$345.52			CMS final 2014 National Limit Amount for CPT code 81275 and CPT code 8140425 (KRAS and NRAS genetic tests)
Administration costs	Panitumumab		Cetuximab
Anti-EGFR + FOLFOX/FOLFIRI				Estimated from billing components for anti-EGFR + FOLFOX/FOLFIRI and CMS costs26 for anti-EGFR + FOLFOX/FOLFIRI
Loading dose	$801.35		$829.29
Maintenance doses	$801.35		$801.35
Cetuximab alone			$133.26	CPT code 9641327
Hospitalization for first administration of anti-EGFR therapy	Panitumumab		Cetuximab
Percentage requiring hospitalization	0.0%		0.0%	The base-case analysis assumed that no patients on either treatment require hospitalization for the first administration
Cost of hospitalization	$0.0			Base case assumed no inpatient hospitalization
Pre-medication costs for anti-EGFR therapy	Dose		Cost per dose
Diphenhydramine drug cost
Average sales price	50 mg		$0.68	HCPCS code J1200 from Payment Allowance Limits for Medicare Part B Drugs19
WAC	50 mg		$0.82	WAC for NDC 00641-0376-21 from the Red Book20
Administration cost	$30.09		CPT Code 9636728
Percentage of doses requiring pre-medication	Panitumumab		Cetuximab	Assumption
First dose	0.0%		100.0%	Minimum pre-medication from cetuximab prescribing information17 is an H1 antagonist (e.g., 50 mg of diphenhydramine or equivalent) IV 30–60 min prior to first dose. Pre-medication for subsequent infusions is based upon clinical judgment and presence/severity of prior infusions. Pre-medication for panitumumab is not required, but can be administered if a patient has had an infusion reaction. We assumed no panitumumab-treated patients and all cetuximab-treated patients would be given pre-medication for the first infusion. We assumed the percentage of patients observed to have an infusion reaction in ASPECCT (Grade 1, 2, 3, or 4) would require pre-medication for the maintenance doses.
Maintenance doses	2.8%		12.5%
Adverse event incidence	Panitumumab		Cetuximab	Source
Infusion reactions				Table 12-8. Overall Subject Incidence of Adverse Events of Interest (Safety Analysis Set) from the ASPECCT Clinical Study Report
Grades 1 and 2	2.6%		10.7%
Grades 3 and 4	0.2%		1.8%
Adverse event cost	Input value
Infusion reactions				Costs for infusion reaction extracted from Foley et al.29, with Grade 1 and 2 reactions assumed to be handled in the outpatient setting and Grade 3 and 4 reactions assumed to be handled via an emergency department visit or inpatient hospitalization. Both costs were calculated as the incremental cost of having the reaction vs not having a reaction (i.e., total costs for those with reaction minus total costs for those without reaction).
Grades 1 and 2	$3,387
Grades 3 and 4	$14,454

^aPercentage doses administered refers to the expected number of doses divided by the observed number of doses in the trial. These values are multiplied by the progression-free survival time divided by cycle frequency to estimate the number of administrations for each regimen.

5-FU, 5-fluorouracil; CMS, Centers for Medicare and Medicaid Services; CPT, Current Procedural Terminology; EGFR, epidermal growth factor receptor; FOLFIRI, 5-fluorouracil + leucovorin + irinotecan; FOLFOX, 5-fluorouracil + leucovorin + oxaliplatin; HCPCS, Healthcare Common Procedure Coding System; IV, intravenous; NDC, National Drug Code; NHANES, National Health and Nutrition Examination Survey; SD, standard deviation; US, United States; WAC, wholesale acquisition cost.

Analyses conducted

The outcomes calculated by the model for panitumumab + FOLFOX and cetuximab + FOLFIRI included the cost per one treated patient, the cost per 100 treated patients, the cost savings per one treated patient, and the cost savings per 100 treated patients receiving panitumumab + FOLFOX relative to cetuximab + FOLFIRI. All costs were reported in 2014 US dollars or inflated to 2014 US dollars using the medical component of the consumer price index30.

Results

Base-case results

The cost-minimization model demonstrated lower projected drug acquisition, administration, and adverse event costs for patients who received panitumumab + FOLFOX relative to cetuximab + FOLFIRI in the first-line treatment of WT RAS mCRC. Table 2 summarizes the cost-minimization results of the deterministic (base-case) analysis.

Table 2. Model results.

	Cost per one treated patient			Cost per 100 treated patients
	Panitumumab  + FOLFOX	Cetuximab  + FOLFIRI	Savings per patient	Panitumumab  + FOLFOX	Cetuximab  + FOLFIRI	Savings per patient
RAS test	$346	$346	–	$34,552	$34,552	–
Drug acquisition	$152,425	$170,404	−$17,979	$15,242,526	$17,040,431	−$1,797,904
Anti-EGFR	$146,988	$165,528	−$18,539	$14,698,816	$16,552,762	−$1,853,946
FOLFOX/FOLFIRI	$5,436	$4,870	$566	$543,649	$487,047	$56,601
Pre-medication	$0.61	$6.21	−$5.60	$61	$621	−$560
Administration	$26,330	$30,972	−$4,642	$2,633,032	$3,097,188	−$464,156
Outpatient	$26,330	$30,972	−$4,642	$2,633,032	$3,097,188	−$464,156
Hospitalization	–	–	–	–	–	–
Adverse event	$118	$622	−$504	$11,790	$62,220	−$50,430
Infusion reactions, Grades 1 and 2	$89	$364	−$275	$8,876	$36,358	−$27,481
Infusion reactions, Grades 3 and 4	$29	$259	−$229	$2,914	$25,862	−$22,948
Grand total	$179,219	$202,344	−$23,125	$17,921,900	$20,234,390	−$2,312,490

EGFR, epidermal growth factor receptor; FOLFIRI, 5-fluorouracil + leucovorin + irinotecan; FOLFOX, 5-fluorouracil + leucovorin + oxaliplatin.

The results presented in Figure 3 show the component costs that are included in the total cost per patient treated for each of the regimens modeled. The model projected a total cost savings of $23,125 (11.4%) per patient treated with panitumumab + FOLFOX (Figure 4).

Figure 3. Total cost per treated patient. FOLFOX = 5-fluorouracil + leucovorin + oxaliplatin. FOLFIRI = 5-fluorouracil + leucovorin + irinotecan.

Figure 4. Cost savings per patient with panitumumab + FOLFOX (5-fluorouracil + leucovorin + oxaliplatin).

Discussion

Summary of results

We developed a cost-minimization model to compare the costs of administering either panitumumab or cetuximab combined with chemotherapy in the first-line setting of WT RAS mCRC. Although no head-to-head trials have been conducted in first line comparing these treatments, the analysis assumed similar clinical efficacy based on third-line results from the ASPECCT trial. Base-case assumptions included, in particular, the acquisition cost of panitumumab + FOLFOX compared with cetuximab + FOLFIRI with all patients with mCRC tested for RAS mutations. The time horizon was based on mean progression free survival calculated using best fit Weibull model survival curves derived from the PRIME trial testing panitumumab in the first-line setting.

The results of this model revealed cost reductions favoring panitumumab in all cost categories, including drug acquisition, drug administration, and adverse events treatment. The overall cost per patient for first-line treatment was $179,219 for panitumumab + FOLFOX vs $202,344 for FOLFIRI + cetuximab, resulting in a per-patient savings of $23,125 (11.4%). The majority of the cost savings in the panitumumab treatment ($17,979 [10.6%]) came from lower anti-EGFR drug acquisition costs, even in the face of higher drug acquisition costs of FOLFOX compared with FOLFIRI. Both administration costs and adverse event management costs were lower with panitumumab + FOLFOX. From a value perspective, this model supports panitumumab as a preferred approach for patients with WT RAS mCRC requiring systemic therapy.

Limitations

As with any model, there are several limitations to this cost-minimization analysis. In the absence of first-line studies directly comparing EGFR antibodies to each other with chemotherapy, mean PFS was set to identical values for both regimens. An assumption was also made that the percentage of doses of panitumumab and cetuximab given over the first-line period would be identical. It is entirely possible that drug exposure might be variable based on adverse events, acute and chronic toxicity, and interactions with chemotherapy. It was further assumed that chemotherapy would be delivered without alteration through the entire first line, an assumption that is unlikely to be completely accurate as cumulative toxicity often limits one or more components31. The model also does not take into account dose reductions and modifications that are more heterogeneous in actual clinical practice compared with those observed during clinical trial management.

Additionally, the model assumed no hospitalization in either arm. However, patients with severe (Grade ≥ 3) infusion reactions often are hospitalized for observation and/or treatment. Given a higher infusion reaction rate for cetuximab compared with panitumumab, the model may under-estimate savings for Grade 3/4 reactions. Moreover, the rate of infusion reactions varies by geography, with the southern US much more likely to have a higher incidence of serious reactions32^,33. In this model, we have assumed a similar rate of infusion reactions in the US, as seen in the ASPECCT trial conducted in other countries, which may under-estimate the incidence.

An additional limitation was that the model was not constructed using the alternative chemotherapy regimens with the EGFR antibody. However, similar clinical outcomes have been seen with the FOLFOX and FOLFIRI chemotherapy regimens3^,4^,34. Indeed, current NCCN guidelines recommend either regimen with either biologic agent in the first-line WT RAS setting3^,4.

Patient-level data from the ASPECCT clinical trial were chosen instead of data from the FIRE-3, CALGB/SWOG 80405, or the PEAK clinical trials, because comparisons in those three studies were cetuximab vs bevacizumab in the first two and panitumumab vs bevacizumab in the last one, while the comparison of interest in this model is panitumumab vs cetuximab11^,12^,15^,35.

Comparison with other published models

We compared our analysis to a similar cost-minimization analysis published in Greece comparing panitumumab with cetuximab in the first-line treatment of patients with EGFR-expressing mCRC with non-mutated WT KRAS36. The results of their analysis found panitumumab monotherapy to be a potentially cost-saving option (vs cetuximab monotherapy) in the management of patients with WT KRAS mCRC36. These results were similar to the findings in our analysis demonstrating cost savings in patients with WT RAS mCRC treated with panitumumab.

Suggestions for future research

Future research can refine the cost-minimization model presented herein by addressing clinical practice effectiveness, drug use (infusions), and withdrawal rates from population-based data sets. Therefore, this cost-minimization model could evolve and continue being a useful tool in assessing value-based approaches to effective cancer interventions for patients suffering from WT RAS mCRC.

Conclusion

Our analysis demonstrates that using panitumumab + FOLFOX compared with cetuximab + FOLFIRI would result in $23,125 (11.4%) of savings per-patient over the course of first-line therapy until progression of disease. In the US, it is estimated that ∼132,700 newly diagnosed cases of colon and rectal cancer are expected to occur in 2015, with metastatic disease presenting at diagnosis in 20% of these cases1^,2. Of these 26,540 patients that are candidates for first-line therapy of mCRC, ∼50% have non-mutated WT RAS tumors1^,2^,10. Assuming all 13,270 eligible WT RAS patients were to receive an anti-EGFR antibody + chemotherapy, the model predicts a net saving of ∼$306 million dollars annually if patients received panitumumab + FOLFOX rather than cetuximab + FOLFIRI. Indirect costs, not addressed by the cost-minimization model, also favor panitumumab due to its biweekly schedule of administration compared with weekly cetuximab. Less frequent administration reduces caregiver costs and increases productivity of both patients and caregivers.

Transparency

Declaration of funding

This study was conducted by RTI Health Solutions under the direction of Amgen and was funded by Amgen. Amgen employees made clinical trial data available for analysis, and offered analytical suggestions. The sponsored research did not put limits on freedom to publish or the content of publication.

Declaration of financial/other relationships

CG and HK are employees of RTI Health Solutions, a consultancy firm that received compensation for the overall economic study design, the analysis, and preparation of this manuscript. GH, JH, GM, and BB are employees of Amgen. They also contributed to the analysis and manuscript preparation. MF, an employee of City of Hope Comprehensive Cancer Center, and LS, an employee of The West Clinic, have previously served as consultants to Amgen and received honoraria from Amgen for speaking engagements; however, they did not receive compensation for their contributions to the study design, data analysis, or preparation of this manuscript. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.