Lung immune prognostic index (LIPI) as a prognostic factor in patients with extensive-stage small cell lung cancer treated with first-line chemoimmunotherapy.

INTRODUCTION: The lung immune prognostic index (LIPI) is a biomarker that combines the lactate dehydrogenase (LDH) value and the derived neutrophil/lymphocyte ratio (dNLR). Its prognostic ability has been reported in non-small cell lung cancer (NSCLC) with immunotherapy. In the context of extensive-stage small cell lung cancer (ES-SCLC) with chemoimmunotherapy, its role remains to be determined. METHODS: A retrospective, multicenter study of patients with ES-SCLC who received atezolizumab plus chemotherapy as first-line treatment was conducted. 101 patients were divided into three groups: LIPI good (n = 33), LIPI intermediate (n = 41), and LIPI poor (n = 27). The Kaplan-Meier method was used for analysis of overall survival (OS) and progression-free survival (PFS), using the log-rank test for comparisons. Univariate and multivariate Cox models were developed to assess the LIPI as an independent predictor of survival. RESULTS: The good LIPI group had a significantly longer median PFS than the intermediate and poor LIPI groups: 9.6 vs 5.4 vs 5.2 months, respectively (p < 0.001). Significant differences in OS between good, intermediate, and poor LIPI were also observed, with median OS of 23.4 vs 9.8 vs 6.0 months, respectively (p < 0.001). Multivariate Cox regression analysis for PFS identified liver metastases and intermediate and poor LIPI as worse prognostic factors (p < 0.050). For OS, a worse prognosis was confirmed in both the intermediate LIPI group (HR: 2.18, 95% CI: 1.07-4.41, p = 0.031) and the poor LIPI group (HR: 5.40, 95% CI: 2.64-11.07, p < 0.001). CONCLUSIONS: In patients with ES-SCLC treated with chemoimmunotherapy, an intermediate and poor pretreatment LIPI score was associated with worse PFS and OS prognosis.

Analysis of first-line treatment in older patients with metastasic colorectal cancer.

OBJECTIVE: The purpose of this study was to analyse the effectiveness and safety of first-line treatment of metastatic colorectal cancer (CRCm) in older patients treated in a tertiary hospital. MATERIAL AND METHODS: This was an observational and retrospective study, including patients aged 75 years or older, with CRCm, who received chemotherapy treatment in 2017. The main variables studied were type of treatment, Progression-Free Survival (PFS), Overall Survival (OS), dose reductions, and treatment delays due to adverse events. RESULTS: A total of 59 patients (71.2% men) with a median age of 76 years were enrolled in this study. About 70% presented colon cancer, with the left colon being the most frequent location. They were treated with 9 different schemes, in most cases using polychemotherapy and biological agents. The median PFS and OS was 12 and 30 months, respectively. A total of 23/59 of patients started treatment at doses lower than recommended in the clinical practice guidelines. In terms of safety, 34/59 of patients had at least one dose reduction, and 30/59 suffered one treatment delay. The most frequent adverse reactions were asthenia, peripheral neuropathy, diarrhoea, and palmoplantar erythrodysesthesia. CONCLUSION: Our patients presented baseline clinical characteristics similar to the general adult population, with no tumour characteristics associated with advanced age. The efficacy and toxicity were similar to those in the clinical trials, although our patients had more dose reductions. Considering the heterogeneity of patients and in the absence of clinical trials in the older population, real-life studies can be very useful.

Olaparib as first line in BRCA-mutated advanced ovarian carcinoma: Is it cost-effective in Spain?

OBJECTIVE: To estimate the cost-effectiveness of olaparib after being funded by the Spanish National Health Service (SNHS) as first-line monotherapy maintenance treatment in patients with advanced high-grade serous ovarian carcinoma (HGSOC) and BRCA mutations in Spain. METHODS: A semi-Markov model with one-month cycles was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a time horizon of 50 years. Two scenarios were compared: receiving olaparib vs. no maintenance treatment. The model comprised four health states and included the clinical results of the SOLO1 study, along with the direct healthcare costs associated with the use of first-line and subsequent treatment resources (2020 €). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was also carried out and a cost-effectiveness threshold of €25,000 per quality adjusted life year (QALY) was considered. RESULTS: The introduction of olaparib as a first-line maintenance treatment for advanced HGSOC patients with BRCA mutations implied a cost of €131,614.98 compared to €102,369.54 without olaparib (difference: €29,245.44), with an improvement of 2.00 QALYs (5.56 and 3.57, respectively). Therefore, olaparib is cost-effective for advanced HGSOC patients with BRCA mutations, with an incremental cost-effectiveness ratio of €14,653.2/QALY. The results from the PSA showed that 92.1% of the simulations fell below the €25,000/QALY threshold. The model showed that olaparib could improve the overall survival by 2 years, vs. no maintenance treatment. CONCLUSIONS: Olaparib as first-line maintenance treatment is cost-effective in advanced HGSOC patients with BRCA mutations in Spain.

Dacomitinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: To assess the cost-effectiveness of first-line treatment with dacomitinib compared with gefitinib in patients newly diagnosed with advanced NSCLC EGFR-positive in the context of Spain. Materials & methods: A partitioned survival model was developed including costs, utilities and disutilities to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with dacomitinib versus gefitinib. Results: Dacomitinib presented higher QALYs (0.51) compared with gefitinib (0.45). Dacomitinib costs were €33,061 in comparison with €26,692 for gefitinib arm. An incremental cost-effectiveness ratio of €111,048 was obtained for dacomitinib. Conclusion: Dacomitinib was more effective in terms of QALYs gained than gefitinib. However, to obtain a cost-effectiveness alternative, a discount greater than 25% in dacomitinib acquisition cost is required.

Network meta-analysis of first-line treatments in transplant-ineligible multiple myeloma patients.

OBJECTIVES: Multiple myeloma (MM) is a complex disease. Lack of direct comparisons among treatments and incorporation of new alternatives make it necessary to perform studies that allow for clinical decision-making. A network meta-analysis (NMA) was developed to evaluate the comparative efficacy among different therapeutic alternatives in newly diagnosed transplant-ineligible MM patients. METHODS: MEDLINE® and EMBASE® were systematically searched up for these drugs: lenalidomide, thalidomide, bortezomib, and daratumumab. Comparative phase II-III randomized clinical trials (RCTs) were included. Progression-free survival (PFS) was selected as efficacy outcome. The NMA was developed using Bayesian methods. Fixed- and random-effects models were assessed using deviance information criteria. RESULTS: The systematic search yielded 593 results. Ten RCTs were included. No differences were observed between fixed- and random-effects models. The combination of daratumumab, bortezomib, melphalan, and prednisone showed the best HR in PFS (reference treatment). Along with this scheme, the best PFS results were obtained by combination of daratumumab, lenalidomide, and dexamethasone (HR 1.2, 95% CrI 0.64-2.4) and bortezomib with lenalidomide and dexamethasone (HR 1.6, 95% CrI 0.81-3.0). CONCLUSIONS: Schemes with the best PFS results were daratumumab treatments and combination of bortezomib, lenalidomide, and dexamethasone, although the latter scheme has been analyzed in heterogeneous populations.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: Osimertinib improves progression-free survival in first-line EGFR mutation-positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR-TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR-TKIs. An incremental cost-effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimertinib was more effective in terms of QALYs gained than comparators (erlotinib-gefitinib). However, to obtain a cost-effectiveness alternative, a discount greater than 60% in osimertinib acquisition cost is required.

Cost-effectiveness of lenalidomide maintenance in patients with multiple myeloma who have undergone autologous transplant of hematopoietic progenitor cells.

The objective of this article is to analyze the ratio of cost-effectiveness and budgetary impact of lenalidomide treatment in patients with multiple myeloma who have undergone autologous transplant in Spain. The analyses were based on clinical trials CALGB 100104 and IFM 2005-02, from the perspective of the National Health System. The alternatives compared were the treatment with lenalidomide against maintenance without treatment (MwT). Efficiency measures used were years of life gained (YGs) and quality-adjusted life years (QALYs). According to the CALGB 100104 trial data, the average health costs of patients who were treated with lenalidomide for 120 months was €836,534.31 and without treatment was €528,963.63. The effectiveness of the lenalidomide group was 7.59YGs (5.72 QALY) against 6.58 of MwT (4.61 QALY). The incremental cost-utility ratio (ICUR) was €277,456.72/QALY and the incremental cost-effectiveness ratio was €303,191.05/YGs. From the analysis, the IFM2005-02 trial obtained 5.13 QALY in the lenalidomide group against the 4.98 QALY in the MwT group, with an ICUR of €1,502,780.55/QALY. In terms of budgetary impact, a range between 799 and 1452 patients susceptible to receive treatment with lenalidomide was assumed in Spain. In conclusion, the results show a high ICUR and budgetary impact, which adds uncertainty about the maximum prudent duration of the treatment.

Trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel in the neoadjuvant setting of HER-2 positive breast cancer.

BACKGROUD: Neoadjuvant treatment based on the combination of trastuzumab plus chemotherapy is the standard of care in patients with HER2-positive early or locally advanced breast cancer. The concurrent use of trastuzumab, anthracyclines and taxanes is frequently used in this setting despite the potential cardiotoxicity of both anthracyclines and trastuzumab. However, not much information is available about this chemotherapy scheme. OBJECTIVE: We wanted to evaluate the efficacy and safety profile of the combination of trastuzumab, liposome-encapsulated doxorubicin and paclitaxel as neoadjuvant scheme. We also tried to establish predictive factors of pathologic complete response. SETTING: The study was carried out in a tertiary University Hospital of Spain. METHOD: This is a descriptive study of the clinical practice performed in our hospital. MAIN OUTCOME MEASURE: Efficacy was measured in terms of pathologic complete response, which was defined as the absence of invasive cancer cells in the breast and the axilla after neoadjuvant treatment. RESULTS: Thirty patients were included, the median age was 48. Seventeen (56.7 %) were hormonal receptor (HR) positive, 14 (46.6 %) had IIIa-b clinical stage and one of them had inflammatory breast cancer. 12 patients (40 %) achieved pCR. Patients with HR-negative BC achieved a higher pCR rate than those ones with HR-positive BC (61.5 % and 23.5 %, respectively; p value = 0.035). 21 patients (70 %) underwent breast conservative surgery. The treatment was in general well tolerated, most frequent grade 3-4 adverse events were neutropenia (20 %), asthenia and liver enzyme alteration (10 %) and febrile neutropenia (6.7 %). No patient developed heart failure, but one (3.3 %) presented a 10 % asymptomatic absolute reduction in left ventricular fraction ejection. CONCLUSIONS: The studied treatment for the neoadjuvant setting of HER2 positive breast cancer seems to be an effective therapeutic option. Despite the expected high rate of cardiotoxicity of this regimen, the study results shows that this treatment regimen appears to be safe. The combination of trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel should be considered for the treatment of HER2-overexpressing breast cancer.