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Background: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown., Materials and Methods: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing., Results: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001)., Conclusion: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Provencio declares consulting fees, payment for lectures, presentations or speakers bureaus and support for attending meetings and/or travel from BRISTOL-MYERS SQUIBB, Astra Zeneca, MSD, Roche, Takeda. This author has also declared that he have a pending patent (n° EP 22 382 701.5). R. Serna-Blasco declares to be in possession of a pending patent (n° EP 22 382 701.5). E. Nadal declares Grants or contracts from Roche, Pfizer, Bristol-Myers Squibb and Merck Serono; consulting fees from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Janssen, AMGEN, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; payment for lectures, presentations or speakers bureaus from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Janssen, Amgen, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre and Qiagen; support for attending meetings and/or travel from Roche, Takeda and Pfizer; and Participation on data safety Monitoring board or advisory board from Roche, Apollomics and MSD. M.P. Diz Taín declares Payment or honoraria for lectures, presentations or speakers bureaus from BRISTOL-MYERS SQUIBB, Astra-Zeneca, Roche, MSD, Takeda, Pfizer and Amgen; support for attending meetings and/or travel from BRISTOL-MYERS SQUIBB, Roche, MSD and Takeda; Participation on a Data Safety Monitoring Board or Advisory Board from BRISTOL-MYERS SQUIBB, Astra-Zeneca, and Boehringer Ingelheim; and other financial or non-financial interests from Astra-Zeneca, Roche, Mirati, and Pfizer. B. Massuti declares consulting fees and support for attending meetings and/or travel from Bristol-Myers Squibb, Takeda, Merck Sharpe and Dohme. J.L. González Larriba declares consulting fees from MSD, Janssen Cilag, Bristol Myers Squibb, Boehringer Ingelheim, and AMGEN; Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Astra Zeneca, Roche, Pfizer, Janssen-Cilag, Novartis, Astella Pharma, and Bristol-Myers Squibb; Support for attending meetings and/or travel from MSD, Takeda, Bristol-Myers Squibb, Roche, Pfizer, and Janssen-Cilag. A. Insa declares Payment or honoraria for lectures, presentations or speakers bureaus from AMGEN, Bristol-Myers Squibb, Roche, and Takeda; Support for attending meetings and/or travel from Roche, Pfizer, and MSD; Participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Sanofi, and Pfizer. A. Sánchez-Hernández declares Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Lilly, MSD, Sanofi, Astra Zeneca, Janssen, Takeda, Merck, Novartis, Pfizer, and Bristol-Myers Squibb; Support for attending meetings and/or travel from Roche, Sanofi, MSD Takeda, Janssen, Pfizer, and Bristol-Myers Squibb. R. García-Campelo declares Grants or contracts from Bristol-Myers Squibb, Astra Zeneca, and MSC; consulting fees from Roche, Bristol-Myers Squibb, MSD, Sanofi, Takeda, Pfizer, Regeneron, AMGEN, and Astra Zeneca. J. Rogado declares Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, MERCK, Ferrer, Persan Farma, Fresenius Kabi, and Sanofi; Support for attending meetings and/or travel from Roche, MSD, Bristol-Myers Squibb, Astra Zeneca, and Lilly; Participation on a Data Safety Monitoring Board or Advisory Board from Fresenius Kabi, MSD, Sanofi. A. Martínez-Martí declares consulting fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, and Pfizer; Payment or honoraria for lectures, presentations, speakers bureaus from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, MSD, and Pfizer; Payment for expert testimony from AstraZeneca/MedImmune; Support for attending meetings and/or travel from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, Pfizer, and Lilly; Participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca/MedImmune, MSD, F. Hoffmann La Roche, Bristol-Myers Squibb. J. Bosch-Barrera declares consulting fees from Sanofi and Roche; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Bristol-Myers Squibb, Astra Zeneca, and Pfizer; Support for attending meetings and/or travel from Takeda and MSD. R. Bernabé-Caro declares an investigational grant Roche; Payment or honoraria for lectures, presentations, speakers bureaus from Roche, Bristol-Myers Squibb, Pfizer, MSD, Amgen, Takeda, and Astra Zeneca; Participation on a Data Safety Monitoring Board or Advisory Board from Takeda, Roche, Bristol-Myers Squibb, and Astra Zeneca. J. de Castro Carpeño declares consulting from fees Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Boehringer Ingelheim, Janssen, Lilly, Sanofi, Takeda, Pfizer, and Glaxo; Payment or honoraria for lectures, presentations, speakers bureaus from Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Pfizer, Janssen, Takeda, and Sanofi; Support for attending meetings and/or travel from Astra Zaneca, MSD, and Hoffmann- La Roche; Participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Glaxo, Janssen, Gilead, and Sanofi. N. Reguart declares Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Guardant Health, Bayer, Merck, Pfizer, Takeda, Novartis, Astra-Zeneca, Janssen Oncology, Sanofi, Eli Lilly, and Amgen; Support for attending meetings and/or travel from Roche, Takeda, and MSD. M. Dómine declares consulting fees and Payment or honoraria for lectures, presentations or speakers bureaus from Astra Zeneca, Bristol-Myers Squibb, MSD, Pfizer, Roche, and Takeda; Support for attending meetings and/or travel from Astra Zeneca, MSD, Pfizer, and Takeda. M. Majem declares Grants or contracts from Roche and Astra Zeneca; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, Pfizer, Helsinn, Cassen, AMGEN, Janssen, Sanofi, Pierre Fabre, Bristol-Myers Squibb, and Takeda; Support for attending meetings and/or travel from Astra Zeneca, MSD, and Roche. A. Estival declares Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Pharmamar, Astra Zeneca, Takeda, Roche, and GSK; Support for attending meetings and/or travel from MSD, Boehringer Ingelheim, and Pharmamar; Participation on a Data Safety Monitoring Board or Advisory Board from Roche and MSD. A. López Martín declares Payment or honoraria for lectures, presentations, speakers bureaus from GSK, Bristol-Myers Squibb, and Astra Zeneca; Support for attending meetings and/or travel from Pfizer and Takeda. M. A. Sala González declares Payment or honoraria for lectures, presentations or speakers bureaus from Takeda and Roche; Support for attending meetings and/or travel from Roche and PharmaMar. M. Cobo declares consulting fees from Novartis, Roche, Astra Zeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, Lilly, Takeda, Pfizer, Kyowa, Sanofi, and Jansen. Payment or honoraria for lectures, presentations or speakers bureaus from Novartis, Astra Zeneca Boehringer-Ingelheim, Bristol-Myers Squibb, Roche, Lilly, MSD, Takeda, Kyowa, Pierre-Fabre, Novocure, Sanofi, and Jansen. I. Barneto declares Payment or honoraria for lectures, presentations or speakers bureaus from Bristol-Myers Squibb, Astra Zeneca, MSD, Takeda, AMGEN, and Novartis; Support for attending meetings and/or travel from MSD and Astra Zeneca; Participation on a Data Safety Monitoring Board or Advisory Board from Sanofi. V. Calvo declares consulting fees from Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Takeda, Sanofi, and AMGEN; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Takeda, Pfizer, and Janssen; Support for attending meetings and/or travel from Astra Zeneca, Roche, and Takeda. A. Collazo declares Payment or honoraria for lectures, presentations or speakers bureaus from Astra Zeneca and Janssen; Support for attending meetings and/or travel from MSD and Takeda. A. Romero declares consulting fees from Takeda; Payment or honoraria for lectures, presentations or speakers bureaus from Illumina, Health in code, and Thermofisher. Support for attending meetings and/or travel from Thermofisher Scientific. Bristol Myers Squibb Foundation, and Takeda; the author also declares a pending patent (n° EP 22 382 701.5). The rest of the authors declare no potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a systematic literature review to identify real-world evidence (RWE) studies and estimated the efficacy and safety of crizotinib using meta-analyses (MA) for objective response rate (ORR), real-world progression-free survival (PFS), and overall survival (OS)., Methods: We searched MEDLINE®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® for published single-arm or comparative RWE studies evaluating patients (N ≥ 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real-world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan-Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first-line crizotinib., Results: Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I 2  > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate)., Conclusion: The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real-world setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ernest Nadal is a consultant for and receives research funding from Pfizer. Nada Rifi and Hannah Le are employees of Pfizer and own Pfizer stock. Imtiaz A. Samjoo, Sarah Kane, Sokhna Mbacke, Lindsey Starkman, and Beatrice Suero are employees of EVERSANA, Canada, a paid consultant to Pfizer in connection with the development of this manuscript. EN is a consultant for and receives research funding from Pfizer. NR and HL are employees of Pfizer and own Pfizer stock. IAS, SK, SM, LS, and BS are employees of EVERSANA, Canada, a paid consultant to Pfizer in connection with the development of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Since specific data on immunotherapy in older adults with advanced non-small cell lung cancer (aNSCLC) are scarce, we designed this study to determine the overall survival (OS) at one year of first-line pembrolizumab in patients older than 70 years with aNSCLC expressing PD-L1. Secondary objectives included progression-free survival, disease-specific survival, response rate, tolerability, quality of life (QoL) changes, and geriatric assessments., Materials and Methods: A single-arm, open-label, phase II clinical trial was carried out by the Spanish Lung Cancer Group between February 2018 and November 2019 at ten active sites in Spain. We included patients 70 years old and older with histological or cytological documented stage IIIB or IV aNSCLC and PD-L1 expression ≥ 1%. Each subject received 200 mg of intravenous pembrolizumab every three weeks for a maximum of two years., Results: 83 patients were recruited for the study and 74 were finally analysed. Most were male (N = 64, 86.5%) and former smokers (N = 51, 68.9%). 24 patients (32.4%) completed at least one year of treatment, 62 (83.7%) discontinued treatment, and 30 (40.5%) experienced disease progression. The median follow-up of our cohort was 18.0 months [range: 0.1-47.7] and 46 patients (62.2%) died during the period of study. The estimated OS at one year was 61.7% (95% CI: 49.6-71.8%) and the median OS of our cohort was 19.2 months (95% CI: 11.3-25.5). QoL tended to improve throughout the study, although the differences were not statistically significant. The main geriatric scores remained stable, except for a worsening in nutritional status (P = 0.004) and an improvement in frailty (P = 0.028)., Conclusion: Our results support treating older adults with aNSCLC expressing PD-L1 with pembrolizumab in monotherapy. The stability of most geriatric scores and the positive trend on the patients' QoL should be highlighted, although our results did not reach statistical significance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Remei Blanco has been awarded grants from AstraZeneca, MSD, and Roche, and Sanofi, has received payment or honoraria from Amgen, AstraZeneca, Boehringer, Bristol-Myers Squibb (BMS), MSD, and Sanofi, has received financial support for attending meetings from Lilly, MSD, and Roche, and has served as a consultant in advisory boards organized by Amgen and Boehringer. Manuel Dómine has received consulting fees for advisory boards from AstraZeneca, BMS, MSD oncology, Pfizer, Roche, and Takeda, has received payment or honoraria from AstraZeneca, BMS, MSD oncology, Pfizer, Roche, and Takeda, and has received financial support for attending meetings from AstraZeneca, MSD oncology, and Takeda. José Luis González Larriba has received payment or honoraria from AstraZeneca, MSD, Novartis, Roche, and Sanofi, has received payment as an expert testimony from AstraZeneca, MSD, and Sanofi, has received financial support for attending meetings from MSD, Pfizer, and Sanofi, and has served as consultant in advisory boards of AstraZeneca, MSD, Sanofi, and Takeda. Juana Saldaña has received payment or honoraria from Roche. Begoña Campos has received payment or honoraria from AstraZeneca, Bayer, BMS, Leo Pharma, Novartis, Pierre Fabre, Roche, and Rovi, has received financial support for attending meetings from BMS, Leo Pharma, Lilly, Novartis, and Roche, and has received consulting fees for advisory boards of AstraZeneca, BMS, and Roche. Andrés Barba has received payment for speaker bureaus from AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, and Sanofi, has received financial support for attending meetings from AstraZeneca, BMS, MSD, Roche, and Novartis, and has served as consultant in advisory boards of BMS and Sanofi. Diego Márquez-Medina has received consulting fees, payment or honoraria, payment for expert testimony, and financial support for attending meetings from AstraZeneca, BMS, MSD, Pfizer, Roche, and Takeda. Ernest Nadal has been awarded grants from BMS, Merck-Serono, Nanostring, and Roche, has received consulting fees and payment or honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer, Janssen, Lilly, Merck-Serono, MSD, Pfizer, Roche, Sanofi, and Takeda, and has served as consultant in advisory boards organized by Apollomics and Roche. All other authors have declared no conflicts of interest related to the present study., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Chemotherapy plus immunotherapy is the standard of care for patients with metastatic NSCLC. No study has evaluated the outcomes of second-line chemotherapy treatments after progression following first-line chemo-immunotherapy., Method: This multicenter retrospective study evaluated the efficacy of second line (2L) chemotherapies after progression under first-line (1L) chemo-immunotherapy, measured by overall survival (2L-OS) and progression free survival (2L-PFS)., Results: A total of 124 patients were included. The mean age was 63.1 years, 30.6 % of the patients were female, 72.6 % had an adenocarcinoma and 43.5 % had a poor ECOG-performance status prior to 2L initiation. Sixty-four (52.0 %) patients were considered resistant to first line chemo-immunotherapy. (1L-PFS < 6 months). In 2L treatments, 57 (46.0 %) patients received taxane monotherapy, 25 (20.1 %) taxane plus anti-angiogenic, 12 (9.7 %) platinum-based chemotherapy and 30 (24.2 %) other chemotherapy. At a median follow-up of 8.3 months (95 %CI: 7.2-10.2), post initiation of 2L treatment, the median 2L-OS was 8.1 months (95 % CI: 6.4-12.7) and the median 2L-PFS was 2.9 months (95 %CI: 2.4-3.3). Overall, the 2L-objective response and 2L-disease control rates were 16.0 %, and 42.5 %, respectively. Taxane plus anti-angiogenic and platinum rechallenge achieved longest median 2L-OS: not reached (95 %CI: 5.8-NR) and 17.6 months (95 %CI 11.6-NR), respectively (p = 0.05). Patients resistant to the 1L treatment had inferior outcomes (2L-OS 5.1 months, 2L-PFS 2.3 months) compared with 1L responders (2L-OS 12.7 months, 2L-PFS 3.2 months)., Conclusion: In this real-life cohort, 2L chemotherapy achieved modest activity following progression under chemo-immunotherapy. 1L-resistant patients remained a refractory population, highlighting a need for new 2L strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Clinical and laboratory parameters associated with response for patients with advanced pre-treated malignant pleural mesothelioma (MPM) are lacking. We aimed to identify prognostic and predictive markers among patients with relapsed MPM who were randomised into the ETOP 9-15 PROMISE-meso phase III trial, evaluating pembrolizumab and chemotherapy., Methods: Baseline clinical and laboratory parameters were investigated for prognostic or predictive value on progression-free survival (PFS) and overall survival (OS) in a retrospective analysis, based on the full cohort of 144 MPM patients. These consisted of immune-inflammatory indexes (neutrophil-lymphocyte ratio [NLR], systemic immune-inflammatory index [SII], lactate dehydrogenase [LDH]) along with other already known prognostic baseline characteristics and laboratory values. Cut-offs were chosen independently of outcome. Based on Cox multivariable analysis for PFS in the whole cohort, a risk factor model was built to illustrate the prognostic stratification of patients by the combination of the derived independent prognostic factors, taking into account the EORTC score, a validated prognostic score in MPM. All models were stratified by histology and adjusted by treatment., Results: In the stratified multivariable analysis in the whole cohort, high SII (hazard ratio (HR) 2.06; 95%CI 1.39-3.05) and low haemoglobin (HR 1.62; 95%CI 1.06-2.50) were associated with worse PFS. Based on these two prognostic factors, a mesothelioma risk score (MRS) was constructed with three PFS risk prognosis categories: favourable, intermediate and poor with 0, 1 and 2 risk factors, respectively (corresponding percent of cohort: 24%, 34% and 42% and median PFS: 5.8, 4.2 and 2.1 months). The derived MRS stratified the prognosis for PFS and OS, overall and within each of the EORTC groups. No significant predictors of treatment benefit were identified., Conclusions: The proposed MRS is prognostic of patient outcome and it fine-tunes the prognosis of patients with pre-treated MPM alone or when used with the already established EORTC score., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRAS G12C , the most common mutation, is found in ~13% of patients. While KRAS was long considered 'undruggable', several novel direct KRAS G12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19., Methods: Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU)., Results: A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates., Conclusions: Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2., (Copyright © 2021. Published by Elsevier B.V.)

Background: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain., Material and Methods: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments., Results: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy., Conclusions: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Chemo-radiotherapy (CRT) and concurrent PD-1 inhibition has shown promising results in pre-clinical models. So far, the feasibility of delivering concurrent CRT and PD-1/PD-L1 inhibition has never been assessed in a clinical trial., Material and Methods: NICOLAS is a phase-II trial evaluating the safety and efficacy of nivolumab combined with CRT in stage III NSCLC. Patients received 3 cycles of platinum-based chemotherapy and concurrent RT (66 Gy/33fractions). Nivolumab started concurrently with RT. The primary endpoint was 6-month post-RT rate of grade-≥3-pneumonitis. A formal interim safety analysis (IA) was scheduled when the first 21 patients reached 3 months follow-up post-RT. An early positive safety conclusion would be reached at IA if there were no grade ≥3-pneumonitis in those patients. Efficacy evaluation was planned provided the safety conclusion was reached., Results and Conclusion: As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade-≥3-pneumonitis was observed by the end of the 3-month post-RT follow-up period. The early safety IA provides evidence that the addition of nivolumab to concurrent CRT is safe and tolerable regarding the 6-month rate of pneumonitis grade ≥3 at the one-sided significance level of 5%. Following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort. NICOLAS trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent CRT in larger prospective trials for locally advanced NSCLC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We present a 45-year-old patient diagnosed with anaplastic lymphoma kinase (ALK)-rearranged metastatic lung cancer who developed grade 4 interstitial lung disease (ILD) while on crizotinib treatment and was lately treated with brigatinib with no reappearance of ILD. To our knowledge, this is the first case report of successful treatment with brigatinib after crizotinib-induced ILD. Even though ILD secondary to brigatinib has been reported in clinical trials, no pulmonary toxicity has been seen in our patient, suggesting no crosslink lung toxicity between crizotinib and brigatinib., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Although concurrent chemotherapy and radiation is the standard approach for good risk unresectable stage III non-small cell lung cancer (NSCLC) patients, there is no optimal concurrent chemotherapy regimen. Administration of chemotherapy at full dose with maximal activity against local and micrometastatic disease is highly desirable. This study tested the feasibility of 3 cycles of full dose cisplatin and pemetrexed concurrent with definitive thoracic radiotherapy followed by consolidation pemetrexed, without the dose-limiting toxicity (DLT) exceeding 33% of the patients., Methods: Patients with unresectable stage III NSCLC, good performance status and no serious comorbidity were eligible. Patients received thoracic radiation to a dose of 66 Gy concurrently with three 21-day cycles of pemetrexed 500 mg/m(2), and cisplatin at escalating doses from 60 to 75 mg/m(2). Consolidation chemotherapy of pemetrexed 500 mg/m(2) was provided for 3 more 21-day cycles. Cisplatin doses were escalated as far as no more than 1/3 of the patients in a level developing dose limiting toxicities (DLT)., Results: Fifteen eligible patients were enrolled: nine in the first dose level and 3 in the second and third dose levels respectively. Two out of 9 patients in the first dose level experienced DLT (grade 3 esophagitis resulting in delay in treatment administration). The major serious acute toxicities were esophagitis (40%) and febrile neutropenia (20%). With a median follow up time of 22 months, median time to progression and overall survival has not been reached. The rate of survival at 24 months was 57.5% (95% CI: 27.5-87.4%) of the patients., Conclusions: Three systemic dose levels of pemetrexed and cisplatin could be administered concurrently with radiotherapy. The rate of survival at 24 months was encouraging., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)