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BackgroundNivolumab (NIV) is a monoclonal antibody for patients with pre-treated advanced nonsquamous non–small-cell lung cancer (NSCLC). It is necessary to evaluate the cost effectiveness of NIV versus docetaxel (DOC), taking into consideration the expression of programmed death ligand 1 (PD-L1).PurposeCost-effectiveness analysis from the payer’s perspective of NIV versus DOC in patient with nonsquamus NSCLC by expression of PD-L1 test (subgroups:<10% vs.≥10%).Material and methodsEfficacy data were obtained from the CheckMate-057 trial to model the incremental cost-effectiveness ratio (ICER) of NIV versus DOC:Difference of overall survival (OS) between NIV vs. DOC: PD-L1 expression ≥10%: 0.9 life years gained (LYG) and PDL1 expression <10%: −0.03 LYG.Drug costs were estimated considering manufacturing costs plus VAT (4%). NIV: mg/m2; DOC: mg/m2. An adult patient was considered (weight=70 kg; body surface: 1.7 m2) (total doses per administration: NIV: 210 mg; DOC: 127.5 mg). Total treatment costs were estimated with the median of the number of administrations received (NIV: six administrations; DOC: four administrations). Other costs were not considered.Time horizon considered: 1 year.Two different one-way sensitivity analyses were performed to test the robustness of the model. Scenario 1: Difference in OS variation was considered.Variations of ±20% OS were performed:PDL1 expression ≥10%. Interval considered: 0.792 LYG – 1.18 LYG.PDL1 expression <10%. Interval considered: −0.036 LYG – −0.024 LYG. Scenario 2: Cost mg variation was considered. Variations of ±25% were performed.Interval considered: €17.14/mg – €10.28/mg.ResultsTreatment total costs were: NIV: €17,274.60 and DOC: 1167.92€.The ICER observed in the subgroup with PD-L1 expression ≥10% was €16,269.37/LYG. Otherwise, the ICER estimated in patients with PDL1 expression <10% was €536,889.33/LYG.No relevant differences in ICER were observed after both one-way sensitivity analyses were performed (OS variation and cost mg variation).ConclusionNIV vs. DOC is cost effective in patients with non-squamous NSCLC with PD-L1 expression ≥10%, although ICER is high.NIV vs. DOC is not cost effective in patients with non-squamous NSCLC with PD-L1 expression <10%.Reference and/or Acknowledgements1. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med2015;373:1627–39.No conflict of interest

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BackgroundRegorafenib is the third line of treatment used in metastatic colon cancer. One of the most frequent adverse effects of regorafenib is thrombocytopenia that occurred as grade 4 in only 0.4% of patients treated in the CORRECT trial.PurposeTo describe the relationship between the occurrence of severe thrombocytopenia in a patient with metastatic colon cancer treated with regorafenib.Material and methodsThe physician reported to our pharmacy department a severe thrombocytopenia case in a patient treated with regorafenib. The medical history was reviewed to evaluate the possible causality by the Karch-Lasagna algorithm.ResultsA 62-year-old man, diagnosed with colorectal adenocarcinoma, was treated with firstline FOLFOX and bevacizumab and secondline FOLFIRI and aflibercept. Oxaliplatin and bevacizumab had to be discontinued due to feet and hand neuropathy and pulmonary embolism, respectively, and enoxaparin was added. In May 2015, adrenal and pulmonary nodules increased in size and the patient started treatment with regorafenib 120 mg/day for 3 weeks, in 28 day cycles. At this time, platelet count was normal (329 000 cells/µL). After 1 month the patient presented grade 1 diarrhoea, 5 kg of weight loss and 155 000 platelets/µL. 2 months later a control blood test showed severe thrombocytopenia (9000 platelets/μL) that was confirmed in two further analyses. Both regorafenib and enoxaparin were discontinued and a pool of platelets was administered. The clinicians prescribed prednisone 100 mg/24 h for 2 weeks continuing the downward pattern. Substantial improvement was observed 7 days later (38 000 platelets/µL) and in mid-August normal levels returned.The modified Karch-Lasagna algorithm established a ‘probable’ relationship between severe thrombocytopenia and regorafenib treatment in this patient due to the fact of the temporal relationship between the start of treatment with regorafenib and thrombocytopenia occurrence, as well as between treatment discontinuation and improvement in thrombocytopenia.ConclusionDespite being an adverse effect described in the data sheet and clinical trials, this episode of thrombocytopenia was very severe and forced discontinuation of regorafenib and change to another therapy. It was reversible and improved with prednisone. This reaction was reported to the Regional Pharmacovigilance Centre.References and/or AcknowledgementsGrothey A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomized, placebo-controlled, phase 3 trial. Lancet 2013;381:303-12.No conflict of interest.