Adverse Event Management Costs Research Articles

Healthcare Resource Utilization and Economic Burden of Cytokine Release Syndrome and Neurotoxicity in Patients with Relapsed and Refractory Multiple Myeloma (RRMM) Receiving Idecabtagene Vicleucel in Earlier-Line Settings in the KarMMa-3 Clinical Trial

Introduction: Adverse events (AE), such as cytokine release syndrome (CRS) and neurological toxicity (NT), have been associated with chimeric antigen receptor (CAR) T cell therapies. Idecabtagene vicleucel (ide-cel, bb2121), a B-cell maturation antigen-directed CAR T cell therapy, demonstrated deep and durable responses in triple-class exposed (TCE) patients (pts) with RRMM in the pivotal, single-arm, open-label phase 2 KarMMa (3 prior lines of therapy [LOTs]; NCT03361748) (Munshi NC, et al. NEJM 2021;384:705-716) and superior progression-free survival with ide-cel vs standard regimens in the phase 3 KarMMa-3 trial (2-4 prior LOTS; NCT03651128) (Rodríguez-Otero P, et al. NEJM 2023;388:1002-1014). Healthcare resource utilization (HCRU) and costs associated with CRS/NT management were estimated previously for pts receiving ide-cel in the KarMMa trial (McGarvey N, et al. Value Health 2023;26:S89) and suggested low rates of severe (grade ≥ 3) CRS/NT following ide-cel infusion and higher HCRU and costs with increasing AE severity. To further assess resource and economic burden associated with care of treatment-emergent AEs, this analysis evaluated HCRU and estimated cost of CRS/NT management among pts treated with ide-cel in earlier-line settings in the KarMMa-3 study. Methods: In this retrospective study, case report forms from the KarMMa-3 clinical trial database among pts experiencing a CRS and/or NT event that initiated within 90 days post ide-cel infusion were assessed. Pt-level HCRU data, including hospitalizations and length of hospital stay (LOS) (standard inpatient [IP], intensive care unit [ICU] days), diagnostics (eg, lab work, imaging), procedures (eg, dialysis, intubation), and medications (eg, oncology supportive care, prophylactics, other AE management) were identified from CRS/NT onset through resolution. AE management costs were estimated using a micro-costing methodology in which unit costs sourced from public databases or literature (eg, United States Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, IBM ® Micromedex ® RED BOOK ®) were adjusted to 2022 US dollars (USD) using the Consumer Price Index and applied to each HCRU identified. Results: Of 225 pts treated with ide-cel in the KarMMa-3 trial, 203 (90.2%) experienced any grade CRS and/or NT event. Pts experiencing a CRS/NT event had a mean (standard deviation [SD]) age of 61.9 (8.9) years and most were male (123/203 [60.6%]), White (138/203 [68.0%]), and non-Hispanic or Latino (138/203 [68.0%]). The majority (187/203 [92.1%]) of pts experienced less severe CRS/NT events (grade ≤ 2), which resolved quicker and relatively few pts (16/203 [7.9%]) had a more severe (grade ≥ 3) event, which took longer to resolve. Among pts who received ide-cel, the estimated median cost of AE management ranged from USD 17,124 (CRS only grade 1) to USD 181,552 (nonconcurrent CRS or NT grade ≥ 3) (Figure 1). Additional median costs for a pt with a grade ≥ 3 CRS/NT event was USD 31,045 higher than a grade ≤ 2 CRS/NT event. Across AE categories, the main contributors to CRS/NT management were facility costs, namely standard IP hospitalizations and ICU stays. Almost all pts (202/203 [99.5%]) had a standard IP hospitalization; 3.9% (8/203) had an ICU stay (Table 1). The trial protocol required a stay of ≥ 15 days post infusion unless admitted to the ICU; some hospitalization days recorded during the AE overlapped with the protocol-required stay. ICU admissions were more common among pts with CRS/NT grade ≥ 3 (7/16 [43.8%]) than those with grade ≤ 2 (1/187 [0.5%]). Median (range) total LOS was 10 days longer among pts with grade ≥ 3 (14.5 [2-84] days) than those with grade ≤ 2 (4 [1-34] days) CRS/NT. Pts with grade ≥ 3 CRS/NT had higher rates of HCRU than those with grade ≤ 2 for several interventions, such as medications (eg, tocilizumab + corticosteroids: 13/16 [81.3%] vs 63/187 [33.7%]), diagnostics (eg, imaging: 14/16 [87.5%] vs 48/187 [25.7%]), and procedures (eg, dialysis:3/16 [18.8%] vs 0/187 [0%]). Conclusions: Most pts with RRMM treated with ide-cel in the KarMMa-3 trial experienced a CRS and/or NT event, however, few were of high severity (grade ≥ 3). HCRU and costs for CRS/NT increased with AE severity and management. CAR T cell therapies associated with lower-severity AEs and planned interventions to prevent higher-grade AEs may provide an opportunity to better manage HCRU and costs.

Healthcare costs associated with first-line (1L) treatment of patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States (US).

11 Background: In 2023 in the US, 82,290 new cases of bladder cancer and 16,670 related deaths were estimated. Prior analyses assessing the economic burden of la/mUC in the current and evolving treatment landscape have been limited. This study aimed to estimate the direct medical costs of treating patients with la/mUC, from US Medicare and commercial perspectives. Methods: A cost model was developed to estimate annual direct medical care costs in patients with la/mUC eligible for 1L platinum-based chemotherapy (PBC) in 2023. Costs (2023 USD)—including drug acquisition and administration, disease management and adverse event (AE) management—were calculated, including subsequent therapy costs. Inputs included estimated number of treated patients per year, treatment duration, progression-free survival and overall survival with various therapies, AEs incidence, and market shares. Efficacy and safety data were sourced from product prescribing information, epidemiology data from Surveillance, Epidemiology, and End Results (SEER) database and published literature. Market share assumptions were based on market research data. Results: For a hypothetical health plan with 1,000,000 members, 108 and 22 patients with la/mUC from Medicare and commercial perspectives, respectively, were estimated to be eligible for 1L PBC in 2023. Estimated total annual costs per treated patient are shown in the Table below. With market share data comprising 1L PBC, with and without avelumab (AVE) 1L maintenance (61% and 25%) and enfortumab vedotin (EV) + pembrolizumab (PEM) (for cisplatin-ineligible patients, 14%), annual costs of $16,673,645 ($12,861 per treated member per month) and $4,637,226 ($17,852 per treated member per month) were estimated for Medicare and commercial perspectives, respectively. Drug acquisition costs in 1L represented most of the total costs (Medicare, 75%; commercial, 64%). Conclusions: Understanding the economic burden associated with la/mUC treatments may facilitate informed decision making on treatment choice and optimal sequencing. Further real-world studies are needed to assess the impact of these innovative treatments on disease and AE management costs of la/mUC. [Table: see text]

Adverse event costs associated with first-line therapy for advanced non-small cell lung cancer in the United States: An analysis of clinical trials of immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors, such as pembrolizumab, nivolumab, and atezolizumab, have demonstrated substantial survival benefits in patients with advanced non-small cell lung cancer (NSCLC). However, there is limited evidence on their relative safety profiles and adverse event (AE)-related cost burden. OBJECTIVE: To compare the AE management costs of nivolumab plus ipilimumab with and without limited chemotherapy with those of chemotherapy, pembrolizumab plus chemotherapy, and atezolizumab plus chemotherapy in a first-line setting among patients with advanced NSCLC. METHODS: The mean per-patient AE costs were estimated using the incidence of all-cause grade 3/4 AEs with any-grade incidence greater than or equal to 15% and the corresponding costs of AE management in the inpatient setting. AE rates were obtained from individual patient data from the CheckMate 227 and CheckMate 9LA trials for nivolumab plus ipilimumab with/without limited chemotherapy and aggregated data from the KEYNOTE-189 and KEYNOTE-407 trials for pembrolizumab plus chemotherapy and the IMpower130 trial for atezolizumab plus chemotherapy. AE management costs from the third-party payer perspective were estimated based on inpatient medical costs from the 2016 United States Healthcare Cost and Utilization Project National Inpatient Sample. All costs were inflated to 2020 US dollars. RESULTS: Nivolumab plus ipilimumab and nivolumab plus ipilimumab plus limited chemotherapy were associated with lower per-patient grade 3/4 AE costs compared with chemotherapy ($1,708 and $624 lower over the treatment course, respectively). Compared with pembrolizumab plus chemotherapy, nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs in patients with nonsquamous histology (difference: -$4,866) and squamous histology (difference: -$3,795), and nivolumab plus ipilimumab with limited chemotherapy also had lower AE costs for both nonsquamous (difference: -$2,800) and squamous (difference: -$2,753) disease. Similarly, nivolumab plus ipilimumab and nivolumab plus ipilimumab plus limited chemotherapy were also associated with lower AE costs ($11,400 and $8,809 lower, respectively) compared with atezolizumab plus chemotherapy among patients with nonsquamous disease. In particular, nivolumab plus ipilimumab without or with limited chemotherapy were associated with much lower AE costs of hematological AEs compared with chemotherapy and other immune checkpoint inhibitor-based treatments in combination with a full course of chemotherapy. CONCLUSIONS: Nivolumab plus ipilimumab with/without limited chemotherapy was associated with lower AE management costs compared with chemotherapy, pembrolizumab plus chemotherapy, and atezolizumab plus chemotherapy as first-line treatment for advanced NSCLC. The AE cost benefits were largely driven by the lower cost burden for hematological AEs for nivolumab plus ipilimumab with/without limited chemotherapy. DISCLOSURES This study was supported by Bristol-Myers Squibb. The sponsor was involved in all aspects of the work and in the decision to submit the manuscript for publication. Dr Stenehjem has received consulting fees from Bristol-Myers Squibb. Dr Lubinga was an employee of Bristol-Myers Squibb at the time of the study's conduct and holds stock/options. Drs Betts and Wu are employees of Analysis Group, Inc., a consulting company that has received funding from Bristol-Myers Squibb for this research.

Economic Evaluation of Nivolumab Versus Docetaxel for the Treatment of Advanced Squamous and Non-squamous Non-small Cell Lung Cancer After Prior Chemotherapy in China.

To evaluate the economic value of nivolumab versus docetaxel for advanced non-small cell lung cancer (aNSCLC) treatment after platinum-based chemotherapy in adults without epidermal growth factor receptor/anaplastic lymphoma kinase aberrations in China. Partitioned survival models evaluated lifetime costs and benefits of nivolumab versus docetaxel by squamous and non-squamous histologies from a Chinese healthcare payer perspective. Progression-free disease, progressed disease, and death health states were considered over a 20-year time horizon. Clinical data were derived from the CheckMate pivotal Phase III trials (ClinicalTrials.gov identifiers: NCT01642004, NCT01673867, NCT02613507); patient-level survival data were extrapolated using parametric functions. China-specific health state utilities, healthcare resource utilisation, and unit costs were applied. Sensitivity analyses explored uncertainty. Nivolumab resulted in extended survival (1.489 and 1.228 life-years [1.226 and 0.995 discounted]) and quality-adjusted survival benefits (1.034 and 0.833 quality-adjusted life-years) at additional costs of ¥214,353 (US$31,829) and ¥158,993 (US$23,608) versus docetaxel in squamous and non-squamous aNSCLC, respectively. Nivolumab was associated with higher acquisition costs, lower subsequent treatment costs, and lower adverse event management costs than docetaxel in both histologies. Drug acquisition costs, discount rate for outcomes, and average body weight were key model drivers. Stochastic results aligned with the deterministic results. Nivolumab yielded survival and quality-adjusted survival benefits at incremental cost versus docetaxel in aNSCLC. As a traditional healthcare payer perspective was applied, the true economic benefit of nivolumab may be underestimated as not all treatment benefits and costs of relevance to society were considered.

Estimated cost of adverse event (AE) management for patients (pts) with metastatic renal cell carcinoma (mRCC) treated with a VEGFR TKI.

629 Background: Nearly all mRCC pts will be treated with one or more VEGFR TKI, alone or in combination with an immunotherapy (IO) or mTOR-inhibitor, during their therapeutic journey and may experience associated AEs. Evidence from the tivozanib (tivo) TIVO-3 trial suggests that median duration of clinically relevant VEGFR TKI class effect AEs is ≤90 days (range 14-90). Cost of AE management has not been clearly quantified to date. This study aimed to estimate how differences in TKI AE profile may impact treatment cost efficiency, particularly in later line (3L+) settings. Methods: iKnowMed EMR was used to identify mRCC pts from USON or Onmark Network, with matched 3rd party insurance claims, that initiated VEGFR TKI treatment between Jan 2015 and Mar 2021. First occurrence of each VEGFR TKI class effect AE was indexed, and associated costs for 90-day (longest median AE duration) follow-up was captured. To assess burden across different TKIs, average per-patient AE management cost was calculated using incidence data from trials supporting FDA approvals, and weight-adjusted to estimated number of commercially insured 3L/4L pts in a 1,000,000-member plan. Results: 5,958 mRCC pts were identified, of which 4,464 were on at least one TKI regimen. Among those, 1,777 experienced an index AE; 1,072 successfully matched to claims data [median 69 years (range 25-94); 55% ECOG PS 0/1; 69% male], accounting for 1,667 unique index AE cases. Most were on cabozantinib (cabo), axitinib (axi), or pazopanib; lenvatinib (len), sunitinib (sun), and sorafenib were also represented. >80% were TKI only, with the rest TKI+IO (18%) or TKI+mTOR (6%). AE costs largely originated from outpatient visits (range 38-77%), excluding renal failure (58% inpatient). Mean cost per AE ranged from $76 (proteinuria) to $1,687 (mucositis/stomatitis). Overall, estimated costs of managing VEGFR TKI class effect AEs in 3L/4L showed lowest resource burden with tivo, and highest with len+everolimus (len+ev; Table). Conclusions: Average VEGFR TKI AE management costs derived from real-world mRCC pts demonstrated differences in healthcare resource burden, with overall anticipated cost dependent on TKI regimen utilized. [Table: see text]

ABCL-101 Cost-Effectiveness of Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

Polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly increased progression-free survival (PFS) (HR, 0.73; 95% CI: 0.57-0.95) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the POLARIX clinical trial (NCT03274492). The objective of this analysis was to evaluate the cost-effectiveness of Pola-R-CHP vs R-CHOP in frontline diffuse large B-Cell lymphoma (DLBCL). In our cost-effectiveness model, we derived PFS, overall survival (OS), drug utilization, adverse events (AE), and subsequent treatment from POLARIX, including higher utilization of chimeric antigen receptor-modified T-cell therapy (CAR-T) and stem-cell transplantation in the R-CHOP arm compared with Pola-R-CHP arm. Costs included drug acquisition, AE management, routine medical care, subsequent treatments, end-of-life care, and work productivity. A scenario analysis was conducted to assess the future impact of increased second-line CAR-T utilization. We estimated the life years, quality-adjusted life years (QALY), cost impacts, and incremental cost-effectiveness ratio (ICER) of Pola-R-CHP vs R-CHOP. Probabilistic sensitivity analyses (PSA) were performed to assess the impact of uncertainty on cost per QALY-gained outcomes. The ICER of Pola-R-CHP vs R-CHOP was $80,920/QALY gained from a societal perspective and $96,014/QALY gained from a payer perspective. From a societal perspective, the total cost of Pola-R-CHP was $41,159 higher than R-CHOP, primarily due to higher drug costs ($125,623 vs $34,034, respectively). Drug cost offsets for Pola-R-CHP included subsequent treatment costs (-$42,269), routine care (-$1,195), end-of-life care (-$393), and work productivity (-$7,677). AE management costs were $1,069 higher with Pola-R-CHP vs. R-CHOP. Pola-R-CHP resulted in an increase of 0.50 life years and 0.51 QALYs vs R-CHOP. PSA results demonstrated that Pola-R-CHP was cost-effective in 63.0% of simulations at a willingness-to-pay of $150,000/QALY gained from a societal perspective, and 60.8% of simulations from a payer perspective. In the increased CAR-T use scenario, the ICER was $61,220/QALY gained. Pola-R-CHP was projected to be cost-effective vs R-CHOP in previously untreated DLBCL. Our economic model demonstrates an improvement in QALYs with Pola-R-CHP vs R-CHOP and savings in costs relating to DLBCL progression. These cost-effectiveness results reinforce the clinical findings from POLARIX suggesting that Pola-R-CHP should be considered as a frontline standard of care.

Cost comparison of adverse event management among breast and ovarian cancer patients treated with poly (ADP-ribose) polymerase inhibitors: analysis based on phase 3 clinical trials

ABSTRACT Background The economic impact of adverse events (AEs) for poly (ADP-ribose) polymerase inhibitors (PARPis) in ovarian or breast cancer has not been widely evaluated. Objective Compare PARPi-related AE management costs from a US payer perspective. Methods The frequency of treatment-related grade 3–4 AEs was obtained from published clinical trials of PARPis for the treatment of advanced ovarian cancer (AOC), platinum-sensitive recurrent ovarian cancer (PSROC), and metastatic breast cancer (MBC). AE management costs per patient (2020 USD) per treatment course were calculated by multiplying the AE unit costs by the frequency of AEs for each arm of each trial. Sensitivity analyses were conducted according to the lower and upper limits of the 95% confidence interval for AE rates and unit costs, respectively. Scenarios were also performed to explore the uncertainty of outcomes. Results Total AE management costs in AOC were: $3,904, olaparib; $5,595, olaparib plus bevacizumab; and $12,215, niraparib. In PSROC, total costs were: $3,894, olaparib; $6,001, rucaparib; and $11,492, niraparib, and in MBC: $3,574, olaparib; and $9,489, talazoparib. Hematological toxicities were the key drivers of AE management costs for PARPis. Conclusions The main AEs among PARPis were hematological. Olaparib was associated with lower AE costs compared to other PARPis.

Budget Impact of Keytruda for the Treatment of Patients with Recurrent or Metastatic (R/M) and Locally Advanced (LA) Cutaneous Squamous Cell Carcinoma (cSCC) in the United States

<h3>Purpose/Objective(s)</h3> cSCC is a type of non-melanoma skin cancer and represents 20% of skin cancer deaths. When not cured by local therapy, cSCC is associated with mortality rates exceeding 70%. KEYTRUDA, an immuno-oncology therapy, was recently approved by the FDA for the treatment of patients with R/M and LA cSCC that is not curable by surgery or radiation. The objective of this study was to estimate the budget impact of adding KEYTRUDA to a US healthcare plan formulary as a therapy in advanced cSCC. <h3>Materials/Methods</h3> A budget impact model (3-year time horizon) was developed to compare the direct costs of treating R/M and LA cSCC patients with and without the introduction of KEYTRUDA. Comparators included commonly used systemic therapies (cemiplimab-rwlc, cetuximab, cisplatin + paclitaxel and cisplatin + 5-fluorouracilMT). Market shares were estimated from market research data for comparators, and assumed for KEYTRUDA as follows: 30%, 36%, 42% in R/M; and 13%, 15%, 18% in LA for years 1-3 respectively. Costs included drug Wholesale Acquisition Cost, administration, monitoring and Grade 3-5 adverse event management costs. A one-way sensitivity analysis and two scenario analyses (including Q6W schedule for KEYTRUDA, and equal KEYTRUDA and cemiplimab-rwlc treatment durations) were conducted. <h3>Results</h3> In a hypothetical 1 million member health plan, the number of R/M and LA cSCC patients were 60/60/61 and 52/52/53, respectively in years 1-3. Of these, 18/22/25 (R/M) and 7/8/9 (LA) patients receive KEYTRUDA in years 1-3. In R/M cSCC, KEYTRUDA was associated with cost savings of $1.967m over 3 years. In LA cSCC, KEYTRUDA resulted in a 3-year budget impact of $0.425m. In total, the adoption of KEYTRUDA in cSCC population was projected to lead to cost savings of $1.541m over 3 years (7% decrease). The cost saving was driven by the shorter treatment duration of KEYTRUDA versus cemiplimab-rwlc resulting in decreased drug acquisition, administration, and monitoring costs, and a less costly safety profile of KEYTRUDA versus chemotherapies. Sensitivity and scenario analyses indicate sensitivity to time on treatment assumptions. <h3>Conclusion</h3> The introduction of KEYTRUDA for R/M and LA cSCC patients in a hypothetical plan of 1 million members is projected to lead to budgetary savings of 7% over three years. Results are most sensitive to assumed time on treatment.

Adverse event management costs for first-line treatment with cetuximab or panitumumab of RAS wild-type metastatic colorectal cancer patients in Latin America.

203 Background: Anti-EGFR treatment of RAS wild-type metastatic colorectal cancer (mCRC) in Latin America includes cetuximab or panitumumab, added to chemotherapy (cet+CT and pan+CT, respectively). Adverse event (AE) profiles for each regimen may influence the treatment decision. This study aimed to estimate the associated financial impact of AE management in three countries: Argentina (AR), Brazil (BR) and Panama (PA) from a healthcare payer perspective. Methods: We revised a published Microsoft Excel-based economic model to calculate average patient- and population-level costs from a payer perspective of mCRC AE management for first-line cet+CT and pan+CT treatment, using AE frequency and severity data derived from the authorization relevant FDA prescribing information (PI), multiplied by the country-specific unit costs of managing AEs. Costs of AE management were obtained from publicly available sources in each country and converted to US dollars (USD). Country-specific market research data were applied to calculate costs at the eligible mCRC population level. The model structure and input parameters were endorsed by local practising oncologists. Results: A 17.5% (all-grade) and 31.6% (grade 3-4) lower average per patient AE frequency were estimated from the PI, for cet+CT vs pan+CT. Cost results are presented in the table. Projected AE management costs of cet+CT for the eligible mCRC population are $297,643 (AR), $124,981 (BR) and $65,895 (PA), annually, reducing current annual estimated AE costs by $42,181 (AR), $8,548 (BR) and $4,691 (PA). Conclusions: According to the average estimated AE frequencies, patients treated with cet+CT are expected to experience fewer AEs than with pan+CT. According to our analyses, the lower frequency rates could result in lower overall and severe AEs’ management costs, resulting in 12.4% (AR), 6.4% (BR) and 6.6% (PA) lower costs of AE management for cet+CT versus pan+CT.[Table: see text]

Cost-effectiveness analysis of carbetocin versus oxytocin for the prevention of postpartum hemorrhage following vaginal birth in the United Kingdom

Aims To assess the cost-effectiveness of carbetocin versus oxytocin for the prevention of postpartum hemorrhage (PPH) following vaginal birth from the perspective of the UK National Health Service (NHS). Materials and methods A decision tree model was designed to analyze the cost per PPH event avoided associated with utilizing carbetocin versus oxytocin for prophylactic treatment of PPH in women following vaginal birth from a UK perspective. It modelled the potential for women to require an additional uterotonic after prophylaxis, and to still experience a PPH event and receive associated treatment. Inpatient recovery and follow-up periods post-PPH were also included in the model. Costs associated with drug acquisition and administration, PPH management (i.e. additional staffing and possible operating theater and high dependency unit utilization), inpatient hospitalization, and follow-up visits were all considered. Adverse event management costs were not included. Resource utilization varied depending on the severity of the PPH event (as defined by the amount of blood lost). PPH events avoided were estimated. In an exploratory analysis, quality adjusted life years (QALYs) were estimated as well. Results In the deterministic base case, costs were £55 lower and PPH events were 0.0342 lower per woman with carbetocin use compared to oxytocin use. Across the cohort of 100 women the reduction in PPH events led to the largest cost savings (£4,233 saved) out of all cost categories, with total cost savings of £5,495. Carbetocin utilization amongst the entire cohort led to 3.42 avoided PPH events compared to oxytocin utilization, comprised of 3.03 fewer mild/moderate PPH events and 0.39 fewer severe PPH events. Carbetocin utilization led to 0.0001 additional QALYs per woman. Conclusion Carbetocin utilization leads to lower prophylactic treatment costs and less PPH events versus oxytocin when utilized for the prevention of PPH following vaginal birth in the UK.

Cost per Responder Analysis to Assess the Value of CAR-T Therapy for Relapsed or Refractory Multiple Myeloma

New classes of therapies have emerged for treating Relapsed or Refractory Multiple Myeloma (RRMM) patients, including chimeric antigen receptor T-cell (CAR-T) therapies targeting the B-cell maturation antigen. While CAR-T therapies are expected to be a more expensive class of treatment compared to chemotherapy, 1 they have been shown to have a high overall response rate (ORR) and progression-free survival (PFS). 2,3 As newer, more innovative RRMM therapies are developed and brought to market, payers will need to balance their higher efficacy and total treatment costs when assessing potential value. To assess the value of RRMM CAR-T therapies (ciltacabtagene autoleucel [cilta-cel] and idecabtagene vicleucel [ide-cel]), we developed a cost per responder (CPR) model that incorporates efficacy and total cost of treatment.In the absence of head-to-head trial data for CAR-T therapies, indirect treatment comparisons (ITCs) can be used to evaluate comparative efficacy, and the results can be used to inform a CPR model. Matching-adjusted indirect comparisons (MAIC) is a form of ITC that involves matching and adjusting a treatment group from a clinical study with individual patient-level data (IPD) available to a comparator for which only summary-level data are available. This method mitigates potential bias arising from differences in patient characteristics between trials and is widely used and accepted in comparative effectiveness research. Unanchored matching adjusted indirect comparison (MAIC) analyses were used to inform the comparative efficacy of cilta-cel versus ide-cel in our CPR model. MAIC results indicated that cilta-cel was associated with statistically significantly improved ORR (odds ratio [OR]: 87.99 [95% confidence interval [CI]: 20.32, 381.01; p < .0001]), complete response or better (≥CR) rate (OR: 5.96 [95% CI: 2.76, 12.88; p < .0001]) and PFS (hazard ratio [HR]: 0.36 [95% CI: 0.22, 0.59; p < .0001]) when compared with ide-cel. 4To adequately capture total treatment costs for each treatment of interest, CPR models should include all costs related to acquisition and delivery of treatment. Relevant costs of CAR-T therapy for RRMM include the cost of apheresis, bridging therapy, costs of CAR-T acquisition and administration, supportive care and monitoring costs, adverse event management costs, and any costs associated with delivery of inpatient or outpatient clinical services.Preliminary results of the CPR analysis indicate that ide-cel is associated with a cost per ORR of approximately $743,000, a cost per CR or better of $1.66 million and a cost per month in PFS of approximately $55,000. Corresponding results for cilta-cel will be generated after the PDUFA date (November 29, 2021), and presented at ASH 2021.In conclusion, CPR models have significant potential to assist payers in evaluating the value of newer, more innovative RRMM therapies by integrating information on both total costs and efficacy.References1 Pagliarulo N. FDA approves first CAR-T cell therapy for multiple myeloma. https://www.biopharmadive.com/news/fda-car-t-multiple-myeloma-approval-bristol-myersbluebird/597438/#:~:text=The%20pharma%2C%20which%20licensed%20the,other%20approve d%20CAR%2DT%20therapies. Published 27 March 2021. Accessed 22 June 2021.2 Munshi NC, Anderson Jr LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-16.3 Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, in relapsed/refractory multiple myeloma [abstract]. Blood. 2020;136(1 supplement). Abstract 177.4 Martin T, Usmani SZ, Schecter JM, Vogel M, Jackson CC et al. (2021) Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Curr Med Res Opin 1-10. DisclosuresMartin: Sanofi: Research Funding; Oncopeptides: Consultancy; Janssen: Research Funding; Amgen: Research Funding; GlaxoSmithKline: Consultancy. Usmani: Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding, Speakers Bureau; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau. Joseph: Johnson and Johnson: Current Employment, Current equity holder in publicly-traded company. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Valluri: Janssen: Current Employment, Current equity holder in publicly-traded company. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Cohen: Eversana Life Science Services: Current Employment, Other: Eversana Life Science Services was contracted by Janssen to work on this project.. Singh: Eversana Life Science Services: Current Employment, Other: Eversana Life Science Services was contracted by Janssen to work on this project..

The budget impact of adding pralsetinib to a US health plan formulary for treatment of non-small cell lung cancer and thyroid cancer with RET alterations.

BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancers. Thyroid cancer, while generally not as lethal as lung cancer, has a large prevalent population and a rapidly increasing incidence in the United States. Pralsetinib is a highly potent, selective rearranged during transfection (RET) inhibitor indicated for the treatment of RET-positive NSCLC and thyroid cancer tumors. OBJECTIVE: To estimate the budget impact of adding pralsetinib to a 1 million-member US health plan formulary for the treatment of patients with metastatic RET fusion-positive NSCLC, advanced or metastatic RET-mutant medullary thyroid cancer (MTC), or advanced or metastatic RET fusion-positive thyroid cancer (non-MTC). METHODS: A budget impact model with a 3-year time horizon was developed in Microsoft Excel to estimate the number of eligible RET-positive NSCLC and thyroid cancer patients in a plan and quantify associated treatment costs (2020 USD). Comparators in the analyses included pralsetinib, selpercatinib, and cabozantinib, as well as indication-specific use of pembrolizumab, pemetrexed/carboplatin combination, vandetanib, lenvatinib, and sorafenib. Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib. The number of treated patients was based on age- and sex-adjusted incidence of disease, the proportion of patients diagnosed with advanced or metastatic disease, and projected RET testing rates. Treatment duration was based on progression-free survival or duration of response data from clinical trials. Medical resources were monetized using standardized sources such as Medicare reimbursement and wholesale acquisition cost (WAC). RESULTS: The model estimated that there would be approximately 6 new treatment-eligible patients in a 1 million-member plan annually. Monthly WAC is $19,243 for pralsetinib and $20,600 for selpercatinib at the recommended starting dose. Adoption of pralsetinib, with corresponding increases in pralsetinib market share, would be slightly cost saving to a payer, decreasing the overall budget impact to the health plan by $49,985 in year 3 (-$0.0042 PMPM; -$0.0030, -$0.0006, and -$0.0005 for NSCLC, MTC, and thyroid cancer [non-MTC], respectively). In year 3, drug costs were the key driver of total costs (~80%-98%) and cost savings. All other medical resource categories were cost-neutral or nominally cost saving or additive in the budget impact analysis. CONCLUSIONS: Quantifying the budget impact associated with the adoption of new targeted precision therapies is an important consideration for payers. For eligible NSCLC and thyroid cancer patients, our analysis suggests that adoption of pralsetinib is expected to result in modest cost savings for US payers. DISCLOSURES: Support for this study was provided by Blueprint Medicines Corporation. This study was conducted by Veritas Health Economics Consulting, Inc., in collaboration with Blueprint Medicines, which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Duff is an employee of Veritas Health Economics Consulting, which received research funding from Blueprint Medicines to develop the budget impact model. Norregaard and Sullivan are employees of Blueprint Medicines. Bargiacchi and Brener were employees of Blueprint Medicines at the time of the research study. This study was presented as a poster at the AMCP Virtual Learning Event, April 2021.

PCN48 Cost-Benefit Analysis of Trilaciclib for the Prevention of Chemotherapy-Induced Myelosuppression in Extensive-Stage Small Cell Lung Cancer

Evaluate the net monetary benefit (NMB) of trilaciclib when used to prevent chemotherapy-induced myelosuppression (CIM) in patients with extensive-stage small cell lung cancer (ES-SCLC). A decision tree model was constructed to calculate the NMB associated with trilaciclib, a myelopreservation therapy. Health outcomes and related economic consequences were projected and compared for adult patients receiving trilaciclib or placebo prior to treatment with standard first-line (etoposide, carboplatin, and atezolizumab) or second-line (topotecan) anticancer regimens. Rates of hematologic adverse events (AEs) consequent to CIM and their reduction due to trilaciclib were imputed from trilaciclib clinical trials. Drug expenses were calculated from published wholesale acquisition costs at recommended dosing. AE management costs were obtained from published literature. Quality-of-life measures were derived from patient-reported outcomes data collected in trilaciclib clinical trials, and quality-adjusted-life-year (QALY) was transformed into a monetary value using willingness-to-pay thresholds. The time horizon was set to the duration of each chemotherapy-based regimen during which CIM events were observed. Assumptions and uncertainty in model parameters were tested using sensitivity analyses. Evaluations were undertaken from a US payer perspective and expressed in 2019 USD. Incremental budget expenses associated with add-on trilaciclib therapy were offset by savings attributed to a reduction in the incidence and costs of patients’ CIM-related AEs. Overall healthcare costs were estimated to be $15,014 and $19,642 lower for both first- and second-line recipient populations, respectively. In parallel, the NMB of trilaciclib was computed to be $15,244 and $21,081 for each corresponding cohort at a conservative $50,000/QALY willingness-to-pay when given as a preemptive intervention. Our model predicts the use of trilaciclib prior to chemotherapy leads to positive NMB in patients with ES-SCLC owing to downstream improvements in QALY and reduced healthcare costs. Economically, trilaciclib is a favorably valued innovation for preventing myelosuppression in patients with ES-SCLC.

Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland.

ObjectiveThe study aim was to evaluate the cost effectiveness and budget impact of siponimod compared to interferon beta-1a for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease, from a Swiss health insurance perspective.MethodsWe conducted an analysis using a Markov cohort model with a cycle length of 1 year, life-long time horizon, and discount rate of 3% for cost and health outcomes. We used a matching-adjusted indirect comparison to estimate clinical outcomes using data from the EXPAND randomised controlled trial of siponimod vs placebo and the Nordic SPMS randomised controlled trial of interferon beta-1a vs placebo as the basis for estimates of disability progression and relapse outcomes. We used 6-month confirmed disability progression results to estimate disability progression in the base-case analysis. We calculated quality-adjusted life-years (QALYs) based on an external study that administered the EQ-5D-3L questionnaire to European patients with multiple sclerosis. We included costs (Swiss Franc (CHF), year 2020) of drug acquisition/administration, adverse events and disease management. We also performed a budget impact analysis to estimate the cost over the first 3 years of introducing siponimod.ResultsFor the base case, siponimod resulted in mean incremental costs of CHF 84,901 (siponimod: CHF 567,838, interferon beta-1a: CHF 482,937) and mean incremental QALYs of 1.591 (siponimod: 7.495, interferon beta-1a: 5.905), leading to an incremental cost-effectiveness ratio of CHF 53,364 per QALY gained. In the probabilistic sensitivity analysis, the probability of the cost effectiveness of siponimod assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained was 90%. Siponimod was projected to result in drug administration costs for siponimod of CHF 23,817,856 in the first 3 years after introduction, accompanied by large cost offsets in drug acquisition of other multiple sclerosis drugs. Considering drug administration, monitoring and adverse event management costs, it was estimated to result in additional healthcare costs in Switzerland of CHF 2,177,021.ConclusionsIn the base-case analysis, we found that siponimod may be cost effective for treating Swiss adult patients with SPMS with active disease. The results of the cost-effectiveness analyses are valid under the assumption that the efficacy of siponimod and the comparators on disability progression for the overall SPMS population would be the same in the active SPMS population.Clinical Trial IdentifierNCT01665144. This economic evaluation was based on the EXPAND trial.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-021-01023-8.

Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel–treated patients in the TRANSCEND NHL 001 trial

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

Cost Effectiveness Analysis of Tisagenlecleucel for the Treatment of Adult Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma in Japan

There are limited treatment options and substantial unmet needs for adult patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) in Japan. In 2019, tisagenlecleucel, a CD19-directed chimeric antigen receptor T cell therapy, was approved for r/r DLBCL in Japan. The efficacy and safety of tisagenlecleucel were demonstrated in the pivotal phase II single-arm JULIET trial. The objective of the current study was to assess the cost-effectiveness of tisagenlecleucel treatment strategy versus current standard of care (salvage chemotherapy treatment strategy) for the treatment of patients with r/r DLBCL in Japan. A three-state partitioned survival model was constructed from a Japanese public healthcare payer's perspective, with the following three health states: progression-free survival, progressive/relapsed disease, and death. Because the tisagenlecleucel arm included patients who did or did not receive the infusion, a decision-tree structure was used to partition patients based on their infusion status. Treatment efficacy and costs were based on tisagenlecleucel-infused patients for those who received the infusion; for non-infused patients, they were based on standard salvage chemotherapy. The efficacy inputs for tisagenlecleucel-infused patients and salvage chemotherapy were based on observed data in the JULIET trial and the international SCHOLAR-1 meta-analysis, respectively, before year 3. Afterward, all patients were assumed to have no further progression and to incur the mortality risk of long-term DLBCL survivors. The base case analysis explored a lifetime horizon (44 years), with costs and effectiveness discounted 2.0% annually, and it used a monthly model cycle. Direct costs were considered in the base case, composed of pretreatment costs, treatment costs, adverse events management costs, follow-up costs before progression, subsequent SCT costs, post-progression costs, and terminal care costs. Total incremental costs, life years (LYs), and quality-adjusted life years (QALYs) were compared for tisagenlecleucel versus salvage chemotherapy. The incremental cost-effectiveness ratio (ICER) was estimated as the costs per QALY gained, and a threshold of ¥7.5 million was used to assess whether tisagenlecleucel is cost effective. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel and salvage chemotherapy were 7.24 and 4.35 years, respectively; the corresponding QALYs were 5.42 and 2.57 years, respectively. The discounted incremental LYs and QALYs comparing tisagenlecleucel to salvage chemotherapy were estimated as 2.89 and 2.85 years, respectively. Over a lifetime horizon, the model estimated that tisagenlecleucel had a total incremental cost of ¥15,590,335 (discounted) versus salvage chemotherapy. Tisagenlecleucel was associated with an ICER of ¥5,476,496 per QALY gained compared to salvage chemotherapy. Extensive sensitivity analyses supported the base-case findings. Tisagenlecleucel is a cost-effective treatment strategy for r/r DLBCL compared to salvage chemotherapy treatment strategy from a Japanese public healthcare payer's perspective.

Cost-effectiveness analysis of using innovative therapies for the management of moderate-to-severe ulcerative colitis in Spain

ABSTRACT Background To evaluate the cost-effectiveness of tofacitinib in comparison to vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC) after failure or intolerance to conventional therapy (bio-naive) or first-line biologic treatment (bio-experienced), from the Spanish National Health System (NHS) perspective. Methods A lifetime Markov model with eight-week cycles was developed including five health states: remission, response, active UC, remission after surgery, and death. Response and remission probabilities (for induction and maintenance periods) were obtained from a multinomial network meta-analysis. Drug acquisition – biosimilar prices included – (ex-factory price with mandatory deductions), administration, surgery, patient management, and adverse event management costs (€, year 2019) were considered. A 3% discount rate (cost/outcomes) was applied. Probabilistic and deterministic sensitivity analyses (PSA) were conducted. Results Tofacitinib was dominant versus vedolizumab (both in bio-naive and bio-experienced patients) entailing total cost savings of €23,816 (bio-naïve) and €11,438 (bio-experienced). Differences in quality-adjusted life-year (QALY) were smaller than 0.1 for both populations. PSA results showed that tofacitinib has a high probability of being cost-effective (bio-naïve: 82.5%; bio-experienced: 90.6%) versus vedolizumab. Conclusions From the Spanish NHS perspective, tofacitinib could be a dominant treatment (less costly and more effective) in comparison to vedolizumab, with relevant cost savings and similar QALY gains.

Budget impact analysis of the use of oral and intravenous therapy regimens for the treatment of relapsed or refractory multiple myeloma in Germany

BackgroundIn Germany, several triplet therapies for treating relapsed or refractory multiple myeloma (rrMM) patients have recently been approved. While most of them are administered intravenously, ixazomib-based combination is the only orally bioavailable regimen.ObjectiveTo conduct a 1-year and 3-year budget impact analysis (BIA) of different novel triplets to treat patients with rrMM in second or subsequent therapy lines accounting for costs covered by German statutory health insurance (SHI).MethodsA 3-state partitioned survival model (PSM) was developed to evaluate the budget impact of the following regimens: carfilzomib plus lenalidomide plus dexamethasone (KRd), elotuzumab plus lenalidomide plus dexamethasone (ERd), daratumumab plus lenalidomide plus dexamethasone (DRd), and ixazomib plus lenalidomide plus dexamethasone (IRd). The analysis included direct medical costs such as drug acquisition, comedication and preparation for parenteral solutions, drug administration and other 1-time costs, adverse event management costs and direct non-medical costs, such as transportation costs.ResultsBased on current drug market shares in German healthcare market, the estimated costs after 1 year of treatment was €551 million (KRd), €163 million (ERd), €584 million (DRd), and €95 million (IRd). The total budget impact of €1393 million is mainly driven by drug acquisition and subsequent therapy costs.ConclusionAmong the regimens of interest, the oral-based therapy regimens offered cost advantages over intravenous-based therapy regimens. The higher overall costs of intravenous therapy regimens were attributed primarily to higher drug acquisition costs.

Estimation of total costs in patients with relapsed or refractory diffuse large B-cell lymphoma receiving tisagenlecleucel from a US hospital’s perspective

Aims: This study estimated the total costs associated with tisagenlecleucel treatment in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) based on the JULIET trial from a United States hospital’s perspective.Methods: An economic model was developed to assess the total costs associated with tisagenlecleucel treatment (from leukapheresis to two months post-infusion) in adults (aged ≥18 years) with r/r DLBCL using a fee-for-service approach. Costs were considered during the pre-treatment, tisagenlecleucel infusion, and follow-up periods, and were estimated based on the health resource utilization and safety data from the JULIET trial. Cost components included leukapheresis, lymphodepleting chemotherapy, tisagenlecleucel infusion/administration, inpatient and intensive care unit (ICU) admission, medical professional visits, lab tests/procedures, and management of adverse events (AEs). The base-case model estimated the total costs using observed hospitalization, ICU, and AE data from JULIET, while scenario analyses varied key assumptions related to AEs and hospitalization.Results: The estimated overall cost associated with tisagenlecleucel treatment from leukapheresis to two months post-infusion was $437,927/patient, of which $64,784 (14.8%) was additional to tisagenlecleucel’s list price ($373,000) and the associated administration cost ($143). The top three key drivers of the additional cost were AE management ($30,594; 47.2%), inpatient/ICU not attributed to AEs ($24,285; 37.5%), and lab tests/procedures ($5,443; 8.4%). In the scenario analyses, total costs ranged from $382,702 (no AEs, no hospitalization) to $469,006 (cytokine release syndrome and B-cell aplasia, hospitalization).Limitations: This analysis was limited to two months of follow-up after tisagenlecleucel infusion, which cannot capture long-term safety outcomes associated with the treatment and may underestimate AE costs.Conclusions: The total cost of tisagenlecleucel administration from leukapheresis to two months was estimated at $437,927. In addition to tisagenlecleucel’s price, the main drivers were AE management costs and inpatient/ICU costs. Future studies based on real-world, long-term use of tisagenlecleucel are warranted.

596P - The cost of adverse event management in patients with RAS wild-type metastatic colorectal cancer treated with first-line cetuximab and panitumumab: An Italian healthcare payer perspective

BackgroundIn Italy, previously untreated patients with RAS wild-type metastatic colorectal cancer (mCRC) may receive an epidermal growth factor receptor (EGFR) inhibitor with a chemotherapy regimen (CT). The choice of anti-EGFR, either cetuximab (cet+CT) or panitumumab (pan+CT), depends on various factors, including adverse event (AE) profiles. Although AE profiles will evolve with increasing use and familiarity, the differences in AE profiles can be explored using literature and safety data from the summary of product characteristics (SmPC). The financial impact of these differences on the Italian National Health Service has yet to be estimated. MethodsWe developed a model to estimate costs of AE management. Frequencies of common and very common AEs associated with cet+CT or pan+CT were sourced from the respective SmPC.1,2 Applicable resource use costs were obtained from hospital services price lists from the Ministry of Health using the DRG outpatient tariff.3 The national-level financial impact was calculated from the number of cet+CT–eligible patients with mCRC treated in the first line based on published literature, national guidelines, and pan+CT market share. Inputs were validated by practicing Italian oncologists. ResultsAll-grade AEs were estimated to be 58.1% lower and grade 3/4 AEs were estimated to be 70.2% lower in patients receiving cet+CT than in those receiving pan+CT. Mean costs of AE management per patient treated with cet+CT and pan+CT were estimated at €1,194 and €2,951, respectively, resulting in average savings of €1,758 (59.6%) per patient. Differences are mainly driven by a lower frequency of AEs that are costly to manage, such as GI disorders. Annual savings could reach €2,191,839 for a population of 1,247 cet+CT–eligible patients with mCRC. ConclusionsFewer AEs for cet+CT may result in markedly lower AE management costs vs pan+CT. Although results should be considered together with overall costs and clinical outcomes, cet+CT could decrease cost burden on the Italian National Health Service and AE burden for patients with mCRC. Editorial acknowledgementClinicalThinking, Inc, Hamilton, NJ, USA (funded by Merck Healthcare KGaA, Darmstadt, Germany). Legal entity responsible for the studyMerck Healthcare KGaA. FundingMerck Healthcare KGaA. DisclosureN. Personeni: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono. V. Gebbia: Honoraria (self): Merck; Honoraria (self): Amgen; Honoraria (self): Roche. P. Novelli: Full / Part-time employment: Merck Serono S.p.A. S. Di Matteo: Research grant / Funding (institution): Merck. G. Colombo: Research grant / Funding (institution): Merck. C. Pescott: Full / Part-time employment: Merck Healthcare KGaA. All other authors have declared no conflicts of interest.