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Among patients with limited-stage small-cell lung cancer, overall and progression-free survival were significantly longer with durvalumab adjuvant therapy added to standard concurrent chemoradiotherapy.

In patients with lung cancer, neoadjuvant treatment with nivolumab and chemotherapy resulted in a significantly higher percentage of patients with a pathological complete response than chemotherapy alone.

Patients with advanced non–small-cell lung cancer with a PD-L1 expression level of 1% or more of tumor cells were randomly assigned to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Overall survival was significantly longer among the patients who received nivolumab plus ipilimumab than among those who received chemotherapy.

No standard treatment exists for patients with platinum-refractory advanced type B3 thymoma and thymic carcinoma. In the PECATI trial, we sought to assess the antitumour activity and safety of lenvatinib plus pembrolizumab in this population. In this single-arm phase 2 trial, we recruited participants from 11 hospitals in France, Italy, and Spain. Eligible participants were adults (aged ≥18 years), with an Eastern Cooperative Oncology Group performance status of 0–1, and with relapsed or recurrent histologically confirmed type B3 thymoma or thymic carcinoma, at a metastatic stage of disease, who had received at least one line of platinum-based chemotherapy and had progressed during or after the previous line of chemotherapy, and did not have an autoimmune disorder. Participants received lenvatinib (20 mg orally once a day) combined with pembrolizumab (200 mg intravenously, infused over 30 min on day one of each cycle) in 3-week cycles for a maximum of 35 cycles (2 years), with treatment discontinued for reasons including confirmed clinical or radiological disease progression or unacceptable toxicity. The primary endpoint was 5-month progression-free survival (null hypothesis: 5-month progression-free survival of ≤50%; alternative hypothesis: 5-month progression-free survival of ≥68·6%) assessed by the investigators in the full analysis set. Safety was assessed in all participants who received at least one dose of study treatment. The data cutoff date for the current analyses was July 1, 2024. The trial was registered on ClinicalTrials.gov, NCT04710628, and is ongoing. From May 13, 2022, to Feb 1, 2024, 43 participants were enrolled and started study treatment (18 [42%] female and 25 [58%] male; 27 [63%] White, four [9%] Arabic or North African, one [2%] Albanian, one [2%] Black, and ten [23%] ethnicity missing). Median age was 57 years (IQR 45–66). 36 (84%) participants had thymic carcinoma and seven (16%) had B3 thymoma. Masaoka–Koga stage IVA disease was recorded in 15 (35%) participants and stage IVB in 28 (65%), including 16 (37%) participants with liver metastases. 23 (53%) participants had three or more metastatic sites. 20 (47%) participants had received two or more previous lines of therapy. After a median follow-up of 10·6 months (IQR 7·8–14·7), the study met its primary endpoint, with 5-month progression-free survival of 88·4% (90% CI 79·8–96·7). Treatment-emergent adverse events were reported in 42 (98%) of 43 participants, the most common being hypothyroidism (27 [63%] participants) and fatigue (25 [58%]). Grade 3 or worse treatment-related adverse events were reported in 16 (37%) participants. Serious treatment-emergent adverse events occurred in 17 (40%) participants. Grade 3 or worse immune-related adverse events occurred in six (14%) participants, namely hepatic cytolysis (two [5%] participants), colitis, pneumonitis, and cardiac dysfunction (one [2%] participant each), and myocarditis and encephalitis (one [2%] participant). No treatment-related deaths were reported. Lenvatinib combined with pembrolizumab showed potential as a standard treatment for pretreated advanced B3 thymoma and thymic carcinoma. Although the toxicity profile appeared manageable, close monitoring for toxicity is advised. Investigator-Initiated Studies Program of Merck Sharp & Dohme.

BackgroundNeoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC) has improved pathological responses and survival rates compared with chemotherapy alone, leading to Food and Drug Administration (FDA) approval of nivolumab plus chemotherapy for resectable stage IB-IIIA NSCLC (AJCC 7th edition) without ALK or EGFR alterations. Unfortunately, a considerable percentage of tumors do not completely respond to therapy, which has been associated with early disease progression. So far, it is impossible to predict these events due to lack of knowledge. In this study, we characterized the gene expression profile of tumor samples to identify new biomarkers and mechanisms behind tumor responses to neoadjuvant chemoimmunotherapy and disease recurrence after surgery.MethodsTumor bulk RNA sequencing was performed in 16 pretreatment and 36 post-treatment tissue samples from 41 patients with resectable stage IIIA NSCLC treated with neoadjuvant chemoimmunotherapy from NADIM trial. A panel targeting 395 genes related to immunological processes was used. Tumors were classified as complete pathological response (CPR) and non-CPR, based on the total absence of viable tumor cells in tumor bed and lymph nodes tested at surgery. Differential-expressed genes between groups and pathway enrichment analysis were assessed using DESeq2 and gene set enrichment analysis. CIBERSORTx was used to estimate the proportions of immune cell subtypes.ResultsCPR tumors had a stronger pre-established immune infiltrate at baseline than non-CPR, characterized by higher levels of IFNG, GZMB, NKG7, and M1 macrophages, all with a significant area under the receiver operating characteristic curve (ROC) >0.9 for CPR prediction. A greater effect of neoadjuvant therapy was also seen in CPR tumors with a reduction of tumor markers and IFNγ signaling after treatment. Additionally, the higher expression of several genes, including AKT1, BST2, OAS3, or CD8B; or higher dendritic cells and neutrophils proportions in post-treatment non-CPR samples, were associated with relapse after surgery. Also, high pretreatment PD-L1 and tumor mutational burden levels influenced the post-treatment immune landscape with the downregulation of proliferation markers and type I interferon signaling molecules in surgery samples.ConclusionsOur results reinforce the differences between CPR and non-CPR responses, describing possible response and relapse immune mechanisms, opening the possibility of therapy personalization of immunotherapy-based regimens in the neoadjuvant setting of NSCLC.

The RAS-RAF-MEK-ERK pathway regulates processes involved in the proliferation and survival of cells. mutations, prevalent in approximately 30% of patients with non-small-cell lung cancer (NSCLC), result in constitutive activation of the pathway. Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with mutant pretreated advanced NSCLC. Several trials in combination with other chemotherapy and targeted therapy regimens in lung cancer are ongoing. We review the development of selumetinib in patients with NSCLC, summarize the pharmacodynamic, pharmacokinetic and tolerability characteristics, and the available clinical trial data to understand the role of selumetinib in the treatment of NSCLC.

Introduction: There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the results obtained during pivotal trials, especially regarding patient subgroups. Methods: Nominal group and Delphi techniques were used. Eight Spanish experts in lung cancer (the scientific committee of the project) analyzed the use of immunotherapy monotherapy as first-line treatment in patients with NSCLC and high PD-L1 expression. The expert scientific committee formulated several statements based on a scientific review and their own clinical experience. Subsequently, 17 additional Spanish lung cancer experts were selected to appraise the committee’s statements through two Delphi rounds. They completed a Delphi round via an online platform and voted according to a scale from 1 (strongly disagree) to 10 (strongly agree). The statements were approved if ≥70% of experts voted 7 or more. Results: A total of 20 statements were proposed covering the following areas: (1) general characteristics of pivotal clinical trials; (2) overall main outcomes of pivotal clinical trials; and (3) subgroup analysis. All statements reached consensus in the first round. Conclusions: AT, CEMI, and PEMBRO as monotherapy can be considered the standard of care in patients with advanced NSCLC and high PD-L1 expression (≥50%). Moreover, some differences noted among the drugs analyzed in this document might facilitate treatment decision-making, especially in clinically relevant patient subgroups, when using PD-1/PD-L1 inhibitors. The high level of agreement reached among experts supports the proposed statements.

•Sex is a major factor in disease, but it is seldom taken into account for survival estimations.•Using RWD we confirm that NSCLC females had a significantly better prognosis than NSCLC males.•The effect size of sex on survival is high supporting sex-based medicine as a new paradigm in medical practice. Biological differences between the sexes have a major impact on disease and treatment outcome. In this paper, we evaluate the prognostic value of sex in stage IV non-small-cell lung cancer (NSCLC) in the context of routine clinical data, and compare this information with other external datasets. Clinical data from stage IV NSCLC patients from Hospital Puerta de Hierro (HPH) were retrieved from electronic health records using big data analytics (N = 397). In addition, data from the Spanish Lung Cancer Group (GECP) Tumor Registry (N = 1382) and from a published study available from the cBioPortal (MSK) (N = 601) were analyzed. Survival curves were estimated using the Kaplan–Meier method. A Cox proportional hazards regression model was used to assess the prognostic value of sex. A meta-analysis to compare the outcome for males and females in terms of overall survival (OS) and progression free survival (PFS) was performed. The median OS time was 12 months for males and 19 months for females (overall HR = 0.77; 95% CI: 0.68–0.87; P < 0.001). Similarly, females with stage IV NSCLC harboring an EGFR-sensitizing mutation lived significantly longer than males (median OS: males, 19 months; females, 32 months) with a lower risk of death compared with males (overall HR = 0.75; 95% CI: 0.67–0.84). In addition, female patients benefited more from EGFR inhibitors in terms of PFS and OS (overall HR = 0.45; 95% CI: 0.32–0.64, and HR = 0.62; 95% CI: 0.48–0.80, respectively). Median PFS was 21 months in females and 12 months in males (P < 0.001). Using routine clinical data we confirmed the previous finding that among stage IV NSCLC patients, females had a significantly better prognosis than males. The effect size of the sex was notable, highlighting the fact that survival rates are usually estimated and patients are generally managed without considering the sexes separately, which may lead to suboptimal results.

Background Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). Objective Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. Design A retrospective, cross-sectional, descriptive analysis. Methods We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. Results One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations ( p  < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy ( p  = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. Conclusions This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

Background The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. Patients and methods The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. Results Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours ( p -value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. Conclusions Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.