Data on treatment patterns and outcomes in patients with advanced gastroesophageal adenocarcinoma in daily clinical practice are scarce. Using real-world data from the Spanish AGAMENON-SEOM registry, this retrospective study assessed patient characteristics, treatment patterns, and outcomes for 1L advanced GC/GEJC/EAC.

Treatment patterns for surgically resected esophageal cancer (EC) and gastroesophageal junction cancer (GEJC) vary across Europe. This study describes real-world treatment patterns and outcomes for patients receiving surgery for stage II or III EC or GEJC. In this retrospective, non-interventional chart review, physicians in Europe (UK, France, Italy, Germany, Spain) were asked to provide clinical and treatment data about their EC and GEJC patients. Patients included were ≥18 years old and underwent surgical resection (index) of Stage II or III cancer between October 2017 and October 2018. Data were collected from medical records until death, loss to follow-up, or end of data collection (June 2020). 252 physicians reported data for 734 patients who received surgery for Stage II or III esophageal squamous cell carcinoma (ESCC) (21%), esophageal adenocarcinoma (EAC) (40%), or GEJC (39%). Patients had a mean age of 62.5 years, 80.4% were male, and 84.9% had an ECOG score of 0 or 1 at the time of diagnosis. Over two-thirds of patients received R0 resection (70.5%). For patients who received neoadjuvant therapy, 69.9% did not experience complete pathological response to treatment. The median (IQR) follow-up was 26.0 (18.0-31.0) months. Among the 734 patients, 66.3% (n=487) received neoadjuvant therapy, 31.5% (n=231) of which was neoadjuvant chemoradiotherapy (CRT), 28.3% (n=208) of which was neoadjuvant chemotherapy and 6.5% (n=48) of which was radiation alone. The most common neoadjuvant CRT regimens were cisplatin + 5-FU (26.4%) and carboplatin + paclitaxel (26.4%). The most common neoadjuvant chemotherapy regimens used were docetaxel + oxaliplatin + leucovorin + 5-FU (FLOT; 26%) and cisplatin + 5-FU (15.9). Cisplatin + 5-FU was more common in ESCC patients, while the FLOT regimen was more commonly used in GEJC and EAC patients. Following surgery, a majority of patients (54.1%) did not receive adjuvant therapy. For patients who received neoadjuvant CRT prior to surgery, less than 30 patients in each country received adjuvant treatment. For patients who received neoadjuvant chemotherapy prior to surgery, 50% also received chemotherapy after surgery. Of all included patients, 22.2% experienced locoregional or metastatic recurrence and 6.1% of patients died during the data collection period. Among those who recurred, the median time to recurrence was 6.0 (0.0-26.0) months. This real-world study showed that a majority of stage II/III EC/GEJC patients received neoadjuvant treatment prior to surgery, however, 69.9% still had residual disease (non-pathological complete response). After surgery, the majority of patients did not receive adjuvant treatment which is in line with clinical guidelines, and disease recurrence was common. These observations indicate a high unmet need in this patient population for more effective treatment options in the adjuvant setting.

Esophageal cancer is the 7th most common cancer in Spain, with an incidence of 2,383 cases per year. Patient with EC has significant unmet medical need, poor quality of life and low survival rates. A retrospective, non-interventional survey of 52 Spanish physicians was conducted between August-November 2018. Clinical data were collected from medical charts for patients aged ≥20 years who had initiated through completion or stopping 1/2 line treatment for ESCC and for esophageal adenocarcinoma or BSC at either line of therapy. Excluded were patients with adenosquamous carcinoma, or with Siewert type 1 gastroesophageal junction cancer . The 52 physicians surveyed were aged 46.5±11.44y , 71.2% male, 14.9±5.9y in practice, 93.4% hospital-based, and treated a median of 50 EC patients in the past 2 years. 149 patients were included, with mean age at 1L of 62.8±9.2y and 83.5% male. At diagnosis patients presented the following comorbidities: 28.9% hypertension, 27.5% hyperlipidemia, 23.5% diabetes, 14.8% dysphagia, and 14.1% chronic obstructive pulmonary disease. At 1L, 91.1% of EC patients received active systemic therapy (Cisplatin+5-FU=19.0%) and 8.1% received BSC (ESCC=5.1%; EAC=11.4%). In 2L (n=44), 81.8% (n=36) of EC patients received systemic treatment (docetaxel n=9; 25.0%) and 18.2% (n=8) received BSC (20.0% in EAC vs 16.7% in ESCC). Physician-reported treatment decisions based primarily on personal experience (35%) and side effects (65%). The main 2L treatment goals were extent patients' life (41.7%) and relieve symptoms (29.2%). For 2L ESCC patients, the most common grade 3 or 4 adverse events were fatigue (70%), neutropenia (55%) and anemia (50%). In this real-world survey of Spanish physicians, approximately 1/20 ESCC patients received BSC at 1L, whereas approximately 1/6 ESCC patients received BSC at 2L. Data indicated that physician treatment decision-making, treatment goals, and adverse events show a great unmet need for a more efficacious or a safer/better tolerated 2L ESCC treatment.

Several systemic therapy options are available for advanced renal cell carcinoma (aRCC) and physicians assess the appropriate regimen for each patient based on treatment characteristics. The aim of the study is to determine oncologists' preferences for the characteristics of aRCC treatment in Spain. Observational study based on a discrete choice experiment (DCE), developed in four phases: 1) setting up a scientific committee to lead the project; 2) literature review to identify treatment characteristics; 3) focus groups (5 patients, 8 oncologists) to prioritize characteristics; 4) survey development. Five treatment attributes, with three levels each, were included in the DCE: survival gain (6months, 1.5years, 3years), severe adverse effects (SAEs) (5%, 15%, 30%), health-related quality of life (HRQoL) (worse, maintained, improved), administration mode (oral 1-2/day, intravenous monthly, intravenous every 15 days) and monthly cost (€3000, €5000, €8000). Data were analyzed using a mixed logit model. Relative importance (RI) of attributes was calculated. Additionally, willingness to pay for the treatment (cost assumed by the health system) and maximum acceptable risk (MAR) of SAEs in exchange for clinical efficacy were estimated from the DCE. Sixty-seven oncologists participated in the study (52.2% men, mean age 41.9 years [standard deviation: 8.4]). All attributes/levels were significant (p<0.05), except for monthly intravenous administration and HRQoL maintenance. The highest RI was attributed to survival gain (54.7%), followed by HRQoL (18.0%), administration mode (11.1%), SAEs (10.8%), and treatment cost (5.5%). Higher cost would be accepted for extending survival by 1 month than for reducing SAEs risk by 1%. The MAR in exchange for extending survival by 1 month was 4.2%. From the oncologist’s perspective, survival gain is the primary goal of aRCC treatment. HRQoL, administration mode and SAEs are also important attributes to consider for decision-making, while treatment cost has low impact on treatment election.

Nivolumab (NIVO) and dabrafenib + trametinib (DAB+TRAM) are approved by the European Medicines Agency as adjuvant treatments for resected melanoma. This study compared the cost per recurrence-free survivor and cost per recurrence-free life-year (RFLY) of adjuvant NIVO vs. DAB+TRAM among patients with stage IIIB/C BRAF-mutant cutaneous melanoma in Spain. Recurrence-free survival (RFS) rates and RFLYs were estimated using a matching-adjusted indirect comparison of NIVO and DAB+TRAM based on the CheckMate 238 and COMBI-AD trials. The analysis was performed from the Spanish National Health System (SNHS) perspective. The total treatment costs at 12, 24, and 36 months were estimated based on drug acquisition cost for hospitals in SNHS. The cost per recurrence-free survivor and cost per RFLY were calculated by dividing the total treatment costs by RFS rates and RFLYs of treatment. All costs were presented in 2020 Euros. The RFS rates for NIVO and DAB+TRAM were 71% (95% CI, 64%–80%) and 86% (83%–90%) at 12 months, 64% (56%–73%) and 63% (58%–69%) at 24 months, and 59% (51%–69%) and 54% (49%–60%) at 36 months, respectively. At 12 months, the cost per recurrence-free survivor for NIVO (66,196€; 95% CI, 59,238€–73,971€) was lower than for DAB+TRAM (97,382€; 93,054€–100,902€); this difference increased at 24 months (73,884€ vs 132,934€, respectively) and at 36 months (79,608€ vs 155,090€). Similarly, the cost per RFLY was lower for NIVO than for DAB+TRAM at 12 months (56,805€ vs 88,029€), 24 months (31,446€ vs 49,746€), and 36 months (22,278€ vs 37,011€). The results indicate that NIVO is associated with a substantially lower cost per recurrence-free survival and cost per RFLY. By these measures, NIVO is more cost-effective than DAB+TRAM as adjuvant therapy for stage IIIB/C BRAF-mutant melanoma.

Lung cancer and its treatment may affect several aspects of patients’ lives. Nevertheless, while survival outcomes are frequently assessed, patient-centered outcomes are rarely collected during patient follow-up. Filling this gap, the International Consortium for Health Outcomes Measurement (ICHOM) developed a standard set of variables aimed at following-up of newly diagnosed lung cancer patients. This project aimed to validate and adapt this set of variables to the Spanish setting. Based on the ICHOM standard set and a literature review, the Scientific Committee (SC: 1 oncologist, 3 hospital pharmacists, 2 patients), proposed the main variables to be evaluated during 4 nominal groups (NG) in the Spanish context. The objective of NG (structured discussion) was to reach consensus on the variables (instrument and periodicity) to be included in the Spanish standard set. Overall, 14 hospital pharmacists, 13 oncologists, 4 hospital managers and 3 patients participated in the NGs. Consensus was achieved when ≥75% of participants agreed on the inclusion/exclusion of each variable. When consensus was not achieved among 4 GN, the SC determined its inclusion/exclusion. Selected case-mix variables (instrument) included: demographic [age, sex, education and social-family support], clinical [weight loss, smoking status, comorbidities (Charlson index), pulmonary function (Forced expiratory volume-FEV-1)], tumor [histology, clinical and pathological stage (Tumor node metastasis-TNM), EGFR, ALK, ROS-1, PD-L1] and treatment variables [intent and completion]. Outcomes variables were: degree of health [performance status (ECOG) and quality-of-life (EQ-5D, LCSS)], survival [overall survival and cause of death], quality of death [place of death, end-of-life care and palliative care, death aligned with living will], surgical and therapy acute complications, and others [date of diagnosis and treatment initiation, productivity loss (sick leave)]. Validation and adaptation of ICHOM standard set to the Spanish setting may facilitate its implementation in clinical practice, paving the way to standardize lung cancer variables collection.

The study aimed to assess, from the Spanish National Health System perspective, the incremental cost-effectiveness ratio (ICER) of nivolumab for the adjuvant treatment of adults with melanoma stage III-IV who have undergone complete resection compared to observation ipilimumab and high-dose interferon (HDI). In 28-day cycle length a partitioned survival model comprising recurrence-free, post-recurrence and death was used to estimate the lifetime accumulated cost and benefits in terms of quality-adjusted-life-years (QALYs). Recurrence-free survival (RFS) curves for nivolumab and ipilimumab derived from CheckMate-238. An indirect treatment comparison of CheckMate-238 and CA184-029 was used to estimate RFS for observation and a network meta-analysis (NMA) for HDI RFS. A correlation equation was used to generate nivolumab overall survival (OS) given RFS data. Observation and ipilimumab OS were taken from CA184-029 and HDI OS from the NMA. Subsequent treatments according to recurrence type and adjuvant treatment received were considered. Utilities reflected EQ-5D data from CheckMate-238. Total costs (expressed in €, year 2019 values) included drug cost (exfactory prices) and intravenous administration of adjuvant and subsequent treatments, health-state disease-management and end-of-life costs. A 3% annual discount rate was applied for cost and outcomes. Probabilistic sensitivity analyses (PSA) were performed. Nivolumab provided higher QALYs (11.38) than observation (7.70), ipilimumab (9.28) and HDI (8.21). The lifetime total costs accounted €143,051/patient with nivolumab, versus €98,663 with observation, €246,943 with ipilimumab and €134,621 with HDI. The ICER was €12,052/QALY gained with nivolumab versus observation, and €2,653/QALY versus HDI. Nivolumab resulted a dominant option compared to ipilimumab. In the PSA, 97% (vs observation) and 100% (vs ipilimumab and HDI) of the 1,000 simulations performed were below a €20,000/QALY gained willingness-to-pay-threshold. Nivolumab is a cost-effective option versus observation and HDI and a dominant option compared to ipilimumab for the adjuvant treatment of resected stage III-IV melanoma in Spain.

Nivolumab plus ipilimumab (nivolumab+ipilimumab) is the first immuno-oncology combination that has shown significant, long-term overall survival (OS) benefit for the first-line treatment of adult patients with intermediate- or poor-risk advanced renal cell carcinoma (1L RCC) compared with standard of care (sunitinib). This study assessed the cost-effectiveness of nivolumab+ipilimumab versus sunitinib in 1L RCC patients in Spain. A three-state partitioned survival model was developed (progression-free, progressed disease and death) with a lifetime horizon (40 years) and one-week cycle length. Progression-free survival, OS, time to treatment discontinuation, adverse event and treatment-specific utility data (EQ-5D-3L) was obtained from CheckMate-214 (NCT02231749; 30 months minimum follow-up). Spanish costs for adverse events and drug acquisition were obtained from Isla (2017) and CGCOF, respectively. Costs for drug administration, monitoring and subsequent therapies were taken from ESALUD (2018) ; associated resource use was based on CheckMate-214 and obtained through clinical expert input. An annual discount of 3.0% was applied to both costs and outcomes. Outcomes of interest were total costs, life years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-utility ratio (ICUR). Furthermore, deterministic and probabilistic sensitivity analyses (DSA and PSA) were assessed for robustness of the results. Nivolumab+ipilimumab was associated with higher QALYs versus sunitinib (4.86 versus 3.54, respectively) at increased total cost (€142,450 versus €104,085, respectively). This resulted in an ICUR of €29,146/QALY versus sunitinib. Based on the DSA, the key ICUR drivers were the proportion of patients receiving treatment after sunitinib and the maximum treatment duration for nivolumab+ipilimumab. The model’s robustness was further confirmed by the PSA; nivolumab+ipilimumab had a 54% and 95% probability of being cost-effective at willingness-to-pay thresholds of €30,000/QALY and €50,000/QALY, respectively. Driven by the increased and sustained OS benefit demonstrated in CheckMate-214, nivolumab+ipilimumab is a cost-effective treatment when compared to sunitinib for 1L RCC patients in Spain, considering a willingness-to-pay of €30,000/QALY.

To assess the estimated costs of managing grade 3-4 TRAEs requiring treatment in CheckMate-141. Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, is approved in the European Union for treatment of SCCHN progressing on or after platinum-based chemotherapy. In the phase 3 CheckMate 141 trial, nivolumab significantly improved overall survival vs investigator’s choice (IC) of standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab) in patients with R/M SCCHN. The frequency, grade, and attribution of TRAEs for which treatment was received were extracted from CheckMate 141 patient-level safety data. Grade 3-4 TRAE treatment costs were estimated mostly based on Spanish National Hospital Discharge Database (Conjunto mínimo básico de datos, CMBD) and some based on regional discharge database. Among the 347 patients in the safety population, 236 received nivolumab and 111 received IC. A total of 88 grade 3-4 TRAEs requiring treatment were observed: 28 among patients receiving nivolumab (11.8%) and 60 among patients receiving IC (54.0%). The mean cost of managing grade 3-4 TRAEs per treated patient was 4.15 times higher in the IC arm (1.967€) than in the nivolumab arm (473€) which corresponded to a total cost of managing grade 3-4 TRAE of 111.711,62€ receiving nivolumab and 218.284,66€ in the IC arm. Patients with platinum-refractory R/M SCCHN treated with nivolumab had fewer grade 3-4 TRAEs requiring treatment (11.8% vs 54.0%), lower estimated total costs of managing TRAEs (111.711,62€ vs 218.284,66€), and reduced TRAEs costs per treated patient compared with standard, single-agent systemic therapy (473€ vs 1.967€).

Nivolumab+ipilimumab (N+I) demonstrated superior efficacy and safety outcomes compared with sunitinib (S) as first-line treatment of intermediate-/poor-risk advanced or metastatic renal cell carcinoma (1L RCC) in the CheckMate 214 trial (CM-214; NCT02231749). This study estimated the number needed to treat (NNT) and number needed to harm (NNH) for N+I versus S in 1L RCC. Rates of overall survival (OS), objective response (ORR) per investigator, and treatment-related grade 3/4 adverse events (AEs) over 12, 24 and 36 months were calculated using patient-level data from CM-214 (minimum follow-up: 30 months). NNTs were calculated for OS and ORR as the inverse of the absolute risk reduction between N+I and S among all randomized patients (N+I: 425; S: 422). Similarly, the NNHs were calculated for grade 3/4 AEs among all treated patients (N+I: 423; S: 416). At 12 months, one death would be prevented if 12.67 (95% CI: 7.36-45.30) patients were treated with N+I instead of S, which reduced to 9.00 patients treated (95% CI: 5.55-23.83) at 36 months. The NNT to achieve one additional responder with N+I versus S was 7.06 (95%CI: 4.88-12.76) at month 12. For every 4.13 (95% CI: 3.14-6.05) patients treated with S instead of N+I, one additional patient would have experienced a treatment-related grade 3/4 AE over 12 months. In Spain and Portugal (PT), there are an estimated 2,582 and 526 patients with 1L RCC eligible for treatment with N+I, respectively. If all eligible patients in Spain (and PT) were treated with N+I instead of S, there would be 204 (PT=42) fewer deaths, 366 (PT=74) additional objective responders, and 624 (PT=127) fewer treatment-related grade 3/4 AEs by 12 months. The NNT/NNH analysis showed that N+I provides consistent improved clinical benefits and lower risks of grade 3/4 AEs compared with S among patients with 1L RCC.

HCC is the 9th most common cancer in Spain, with an incidence of 5,878 new cases per year. Patient with HCC has significant unmet medical need, poor quality of life and low survival rates. A retrospective, non-interventional survey of 52 Spanish physicians was conducted between February-March 2018. Clinical and treatment data were collected from medical charts for patients aged ≥18 (with Child-Pugh A/B status at 1L initiation), who initiated and completed systemic 1L treatment for HCC within 2y of data collection. Descriptive statistics compared 1L systemic therapy, sorafenib vs. other. The 52 physicians surveyed were aged.46.0±10.4y (mean±SD), 65.4% male, 14.3±5.6y in practice, 94.2% hospital-based, and treated a median of 30 aHCC patients in the past 2 years. 125 patients were included, with mean age at 1L of 65.3±10.4y and 84.0% male. Patients presented as follows at diagnosis: 62.4% portal vein invasion, 56.8% severe fibrosis or cirrhosis and 46.4% distant metastasis. Comorbidities: alcoholism (32.8%), Hepatitis C (16.0%), Hepatitis B (5.6%), nonalcoholic steatohepatitis or nonalcoholic fatty liver disease (7.4%). Physicians based HCC treatment decisions on: personal experience (38.5%), guidelines (78.9%), and over 90% believe there is a great unmet need for more efficacious aHCC treatment. Of these patients, 75.2% received with sorafenib and 24.8% were offered other treatments. Dose or schedule intensity was reduced significantly in 33.0% of patients receiving sorafenib vs. others 6.5% (p<0.001), and a difference was also shown for treatment duration (p=0.005). The most common grade 3 or 4 adverse events were fatigue (9.6%), hypertension (4.8%), and diarrhea (4.8%). In this Real World chart survey of Spanish physicians, sorafenib remains the most commonly used 1L systemic therapy for aHCC. Understanding determinants of 1L therapy is important as the treatment landscape of HCC is evolving to address unmet need.