SEOM-GECP-GETTHI Clinical Guidelines for the treatment of patients with thymic epithelial tumours (2021)

Chemotherapy; Lenvatinib; Thymic epithelial tumoursQuimioterapia; lenvatinib; Tumores epiteliales tímicosQuimioteràpia; Lenvatinib; Tumors epitelials tímicsThymic epithelial tumours (TET) represent a heterogeneous group of rare malignancies that include thymomas and thymic carcinoma. Treatment of TET is based on the resectability of the tumour. If this is considered achievable upfront, surgical resection is the cornerstone of treatment. Platinum-based chemotherapy is the standard regimen for advanced TET. Due to the rarity of this disease, treatment decisions should be discussed in specific multidisciplinary tumour boards, and there are few prospective clinical studies with new strategies. However, several pathways involved in TET have been explored as potential targets for new therapies in previously treated patients, such as multi-tyrosine kinase inhibitors with antiangiogenic properties and immune checkpoint inhibitors (ICI). One third of patient with thymoma present an autoimmune disorders, increasing the risk of immune-related adverse events and autoimmune flares under ICIs. In these guidelines, we summarize the current evidence for the therapeutic approach in patients with TET and define levels of evidence for these decisions

Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in advanced non-small cell lung cancer

Antibody-drug conjugates, Immune-checkpoint inhibitors; Non-small cell lung cancerConjugats de fàrmac-anticòs; Inhibidors de punts de control immunitaris; Càncer de pulmó de cèl·lules no petitesConjugados de fármaco-anticuerpo; Inhibidores de puntos de control inmunitarios; Cáncer de pulmón de células no pequeñasIntroduction Advanced non-small cell lung cancer (aNSCLC) is an incurable disease. The effort to develop treatments with more effective systemic agents continues. This has led to the FDA approval of one antibody–drug conjugate (ADC) and eight immune checkpoint inhibitors (ICIs) for patients with aNSCLC. Areas covered Due to the demonstrated efficacy of ADCs and ICIs in aNSCLC, treatment combining both agents merits attention. This article, therefore, explores the use of ADCs and ICIs in patients with NSCLC, assesses the scientific rationale for combination treatment, and provides an overview of ongoing trials. It also presents some early efficacy and safety results of such combination use. Expert opinion It is not clear whether ADC-immunotherapy has a significant impact on those with a targetable oncogenic driver alteration since targeted therapies are effective. However, in aNSCLC without a targetable oncogenic driver alteration, the combination of ADCs and ICIs has potential and remains an area of active clinical research

Immunotherapy in small cell lung cancer:One step at a time: A narrative review

Chemotherapy with or without radiotherapy has been the standard of care for many years for patients with small cell lung cancer (SCLC). Despite exceptionally high responses (up to 80%) with chemotherapy, the majority of patients relapse rapidly within weeks to months after treatment completion. Therefore, new and better treatment options are necessary. Recently, synergistic activity has been reported for the addition of immune checkpoint inhibitors (ICI) to standard platinum-based chemotherapy in the therapeutic strategy of advanced SCLC. For the first time after several decades, a significant survival improvement was achieved for this population. However, the overwhelming majority of patients do not respond to ICI, or relapse rapidly. There is need for better knowledge about the biology, histopathologic features, and molecular pathways of SCLC. This can probably help to identify the optimal predictive biomarkers, which are warranted to develop an individual therapeutic strategy including the rational use of a combination of immunotherapeutic agents. Here, we provide an overview of the rationale for and clinical results of the completed and ongoing trials using different strategies of immunotherapy in SCLC. In addition, opportunities for further improvement of therapies will be discussed, including the addition of radiotherapy, co-stimulatory antibodies, and other immune modifying agents.</p

A Delphi consensus panel about clinical management of early-stage EGFR-mutated non-small cell lung cancer (NSCLC) in Spain: a Delphi consensus panel study

Delphi method; Non-small cell lung cancer; OsimertinibMétodo Delphi; Cáncer de pulmón de células no pequeñas; OsimertinibMètode Delphi; Càncer de pulmó de cèl·lules no petites; OsimertinibPurpose This Delphi panel study assessed the level of consensus between medical oncologists on the clinical management of patients with early-stage EGFR-mutated non-small cell lung cancer (NSCLC). Methods A modified two-round Delphi approach was used. A scientific committee comprised of medical oncologists developed an online questionnaire. Delphi panel experts rated their level of agreement with each questionnaire statement on a 9-point Likert scale. The questionnaire included 36 statements from 3 domains (clinical management of early-stage NSCLC: 15 statements; role of adjuvant therapy in early-stage NSCLC: 9 statements; and role of adjuvant therapy in early-stage NSCLC with sensitizing EGFR mutation: 12 statements). Results In round 1, consensus was reached for 24/36 statements (66.7%). Nine statements that did not achieve consensus after the first round were evaluated in round 2, and none of them reached consensus. Overall, 84.4% of the panelists agreed that EGFR mutation testing should be done after surgery. Consensus was not achieved on whether the implementation of EGFR mutation testing in resected early-stage NSCLC could limit the use of adjuvant osimertinib. The panelists recognized the rationale for the use of osimertinib in the adjuvant scenario (88%) and 72% agreed that it may change the treatment paradigm in stage IB–IIIA EGFR-mutated NSCLC. Consensus was not reached on the inconvenience of prolonged duration of osimertinib. Conclusions This Delphi study provides valuable insights into relevant questions in the management of early-stage EGFR-mutated NSCLC. However, specific issues remain unresolved. The expert consensus emphasizes the role of adjuvant treatment with osimertinib in this scenario.The project was funded by ICAPEM (for its acronym in Spanish of Asociación para la Investigación de Cáncer de Pulmón en Mujeres). The opinions expressed are those of the authors. The funding party did not influence any aspect of the study design, collection, analysis or interpretation of data, or decision to submit the manuscript for publication

Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases

International audienc

ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer:ANSELMA

BACKGROUND: Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT. METHODS: Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, main end-point), progression-free survival (PFS) and subgroup analyses. RESULTS: Sixteen trials were available (8,629 patients, 64% adenocarcinoma). AA significantly prolonged OS (HR = 0.93 [95% confidence interval {CI}: 0.89; 0.98], p = 0.005) and PFS (0.80 [0.77; 0.84], p < 0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.8% [-0.4; +4.0] and +3.5% [+1.9; +5.1], respectively. The OS benefit of AA was higher in younger patients (HR = 0.87 [95% CI: 0.76; 1.00], 0.89 [0.81; 0.97], 0.94 [0.87; 1.02] and 1,04 [0.93; 1.17] for patients <50, 50-59, 60-69 and ≥ 70 years old, respectively; trend test: p = 0.02) and in patients who started AA within 9 months after starting the first-line therapy (0.88 [0.82; 0.99]) than in patients who started AA later (0.99 [0.91; 1.08]) (interaction: p = 0.03). Results were similar for PFS. AA increased the risk of hypertension (p < 0.0001), but not the risk of pulmonary thromboembolic events (p = 0.21). CONCLUSIONS: In the 2LT of advanced NSCLC, adding AA significantly prolongs OS and PFS, but the benefit is clinically limited, mainly observed in younger patients and after shorter time since the start of first-line therapy