Manuel David Gil-Sierra

Objective: Patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon 20 insertion mutations have a poor prognosis and few therapeutic alternatives. We conducted a review of scientific evidence about therapies in NSCLC with EGFR exon 20 insertion mutations. Data Sources: A systematic review in PubMed® database was performed up to November 19, 2022. Clinical trials (CTs) about treatments of patients diagnosed with advanced or metastatic NSCLC harbouring EGFR exon 20 insertions who had previously received platinum-based chemotherapy were selected. CTs with a sample size of less than 10 patients were discarded. Efficacy results were used to determine the most interesting drugs. Subsequently, a more exhaustive analysis of the design of the CTs and safety of the most interesting schemes was conducted. Comparisons were attempted to develop. Data Summary: A total of 40 records were found in the systematic search. Twelve selected CTs included the following therapies: poziotinib, osimertinib, pertuzumab–trastuzumab–docetaxel scheme, mobocertinib, amivantamab, erlotinib–onalespib regimen, luminespib, ado-trastuzumab emtansine and dacomitinib. Mobocertinib, amivantamab and poziotinib were determined as the most interesting treatments according to efficacy data. Gastrointestinal and dermatological adverse reactions were relevant in these regimens. All CTs presented a non-randomised design. No reliable comparisons could be developed. Conclusions: The efficacy of mobocertinib, amivantamab and poziotinib in NSCLC with EGFR exon 20 insertion mutations is promising. However, therapies were assessed in single-arm CTs with low-quality evidence. Comparative studies with more extensive patient follow-up, larger sample size and better design are needed to reliably quantify the effect of these drugs.

Patient empowerment is one of the main pillars of humanisation. Therefore, consideration of patients' preferences and expectations should be taken into account during the practice of any healthcare professional. Improving overall survival and quality of life are the main wishes of patients. Indeed, the recent emergence of Patient Reported Outcomes has become an important focus for healthcare providers. The hospital pharmacist specialised in drug evaluation is a professional who evaluates the efficacy, safety, appropriateness and efficiency of treatments prescribed by physicians, and decision- making must be based on both technical factors and the four principles of bioethics. The correct application of evidence-based clinical practice allows to provide patients with increases in survival and/or quality of life, adapting the convenience and costs to the current situation. With this in mind, it could be said that the evaluation of medicines involves a strong commitment to humanisation. On the other hand, organisations that promote the rigorous evaluation and selection of medicines stand as allies of patients, as they have a direct impact on them and an indirect impact on society. Regulatory agencies in charge of approving and financing medicines in healthcare systems play a key role in the process of humanising clinical decision-making and empowering patients. If these agencies approve the use of new medicines based on data that do not measure quality of life or survival of patients when there are already other therapeutic alternatives for these pathologies, they are indirectly failing to meet patients' expectations and are infringing bioethical principles. This can have a considerable influence on the benefit-risk ratio of drugs, and patients may be treated with regimens that do not provide benefit, or may even harm them. Therefore, where should the process of humanisation be oriented? It seems reasonable that the benefit of the patient should be the fundamental objective of the process of humanisation of healthcare, evidently.

Belantamab mafodotin (BLMF) is an interesting therapeutic alternative for multiple myeloma (MM) patients pretreated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Scientific evidence on BLMF provides immature data about progression-free survival and overall survival by short follow-up of patients with poor prognoses. Cases with long follow-ups could provide additional information about BLMF. This case reports a patient with MM treated with BLMF who had received nine previous lines of therapy with a follow-up of 11 months. No complete response was obtained. However, no disease progression was observed and the patient was still alive at the end of this work. BLMF showed manageable adverse effects. Our patient presented advanced disease, good functional status at the beginning of BLMF treatment, and elevated levels of lactate dehydrogenase during BLMF therapy. The influence of these last two factors was not evaluated in clinical trials. This relationship should be assessed more deeply in future studies.

Objective: The European Medicines Agency's marketing authorisation criteria for drugs are reflected in the European Public Assessment Reports. The objective is to describe the expectations and preferences of our onco-hematological outpatients with respect to their oral treatments, and to evaluate the concordance with the results of European Public Assessment Reports.Method: A survey of onco-hematological patients' expectations and preferences about overall survival and quality of life was developed, with three items: expectations on treatment, preferences of benefit and willing-ness to receive novel treatments with non-definitive results. European Public Assessment Reports of the indicated drugs were reviewed. Kappa index (kappa) was used to assess the agreement between patients' expectations and preferences respect to the benefit in overall survival and quality of life described in the corresponding European Public Assessment Report. Con-cordance between willingness of patients to receive novel treatments and European Public Assessment Reports results was evaluated by absolute agreement (Ao). Results: There were 29 participants, and 19 different European Public Assessment Reports were consulted. Patients' expectations about their treatment: 82.1% expected improvement in overall survival and quality of life; the kappa value between expectations and results of European Public Assessment Reports was 0.091 (confidence interval 95%: -0.025 to 0.207). Patients' preferences about benefit of their treatment: 92.6% pre-ferred quality of life; the kappa value was 0.016 (confidence interval 95%: -0.127 to 0.160). Willingness to receive novel treatments: 82.1% parti-cipants demanded benefit in overall survival or quality of life; exigences were met in Ao = 53.6% of patients.Conclusions: Little agreement was observed between expectations and preferences of our onco-hematological patients and European Public Assessment Reports, according to overall survival and quality of life. Most patients preferred an improvement in quality of life, but also expected an increase in overall survival with their treatment. Almost half of patients would not meet their requirements to receive their drug when it was autho-rized.

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Objective: Refractory multiple myeloma (MM) presents poor responses to therapies. New drugs for highly pretreated MM are a hope for this clinical context with limited treatment options. We developed a comparative commentary on the evidence about the use of belantamab mafodotin in heavily pretreated relapsed or refractory MM with respect to other therapies. Data sources: Regimen data were extracted from pivotal clinical trials. Data summary: Response rates were the main efficacy outcomes reported in trials. Overall response was achieved by approximately 30% of patients trated with belantamab mafodotin. Response rates of different regimens must be supported by more relevant data, such as overall survival or progression-free survival. Subgroups of patients with extramedullary disease and revised International Staging System III should be thoroughly evaluated in phase III comparative clinical trials with larger sample sizes. Belantamab mafodotin presented specific adverse events (visual disturbances and kerathopathies). Grade 3–4 adverse events involved high percentages of patients treated with the different schemes. The budgetary impact of different treatments for heavily pretreated refractory MM would be very high. Literature suggested increased efficiency of belantamab mafodotin versus chimeric antigen receptor T-cell therapies. Conclusions: Belantamab mafodotin and other regimens are promising drugs for MM, especially for triple-class refractory patients. Comparative studies are necessary to perform a reliable therapeutic positioning.

Introduction. A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19. Methods. A search in Pubmed (R) database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability. Results. A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution. Conclusions. We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.