561 results found
Scherpereel A, Antonia S, Bautista Y, et al., 2022, First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743., Lung Cancer, Vol: 167, Pages: 8-16
OBJECTIVE: In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs). MATERIALS AND METHODS: Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted. RESULTS: Completion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36-0.74]) and showed a trend in symptom delay versus chemotherapy. CONCLUSIONS: Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM.
O'Sullivan H, d'Arienzo PD, Yousaf N, et al., 2022, Inadequacy of PCR genotyping in advanced non-small cell lung cancer: EGFR L747_A755delinsSS exon 19 deletion is not detected by the real-time PCR Idylla™ EGFR mutation test but is detected by ctDNA next generation sequencing and responds to osimertinib., Eur J Cancer, Vol: 166, Pages: 38-40
Peters S, Scherpereel A, Cornelissen R, et al., 2022, First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743., Ann Oncol, Vol: 33, Pages: 488-499
BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued t
Whisenant JG, Baena J, Cortellini A, et al., 2022, A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry., J Thorac Oncol, Vol: 17, Pages: 661-674
INTRODUCTION: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. METHODS: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. RESULTS: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive
Passaro A, Leighl N, Blackhall F, et al., 2022, ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer., Ann Oncol, Vol: 33, Pages: 466-487
The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.
Fendler A, Shepherd STC, Au L, et al., 2022, Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer., Cancer Cell, Vol: 40, Pages: 438-438, ISSN: 1535-6108
In this report from the CAPTURE study (NCT03226886), we demonstrate that a third dose of COVID-19 vaccine boosts neutralizing antibody (NAb) and cellular responses in patients with cancer, including those that had undetectable NAb titers (NAbT) following two vaccine doses or for whom NAbT waned. We have noted that one key member of the CAPTURE consortium—Sanjay Popat—was inadvertently not included in the author list. We now include him as a co-author. There are no additional changes to the declaration of interests statement, since Dr. Popat declares no competing conflict of interest. This author list change is now reflected in the online version of this letter.
Popat S, Hsia T-C, Hung J-Y, et al., 2022, Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG), ONCOLOGIST, Vol: 27, Pages: 255-265, ISSN: 1083-7159
Coker EA, Stewart A, Ozer B, et al., 2022, Individualised prediction of drug response and rational combination therapy in NSCLC using artificial intelligence enabled studies of acute phosphoproteomic changes., Mol Cancer Ther
We hypothesise the study of acute protein perturbation in signal transduction by targeted anticancer drugs can predict drug sensitivity of these agents used as single agents and rational combination therapy. We assayed dynamic changes in 52 phosphoproteins caused by acute exposure (1hr) to clinically-relevant concentrations of 7 targeted anticancer drugs in 35 non small-cell lung cancer (NSCLC) cell lines and 16 samples of NSCLC cells isolated from patient pleural effusions. We studied drug sensitivities across 35 cell lines and synergy of combinations of all drugs in six cell lines (252 combinations). We developed orthogonal machine-learning approaches to predict drug response and rational combination therapy. Our methods predicted the most and least sensitive quartiles of drug sensitivity with an AUC of 0.79 and 0.78 respectively, while predictions based on mutations in three genes commonly known to predict response to the drug studied e.g. EGFR, PIK3CA and KRAS, did not predict sensitivity (AUC 0.5 across all quartiles). The machine-learning predictions of combinations was compared to experimentally-generated data showed a bias to the highest quartile of Bliss synergy scores, p=0.0243. We confirmed feasibility of running such assays on 16 patient samples of freshly isolated NSCLC cells from pleural effusions. We have provided proof of concept for novel methods of using acute ex-vivo exposure of cancer cells to targeted anticancer drugs to predict response as single agents or combinations. These approaches could compliment current approaches using gene mutations/amplifications/rearrangements as biomarkers, and demonstrate the utility of proteomics data to inform treatment selection in the clinic.
Tiseo M, Popat S, Kim HR, et al., 2022, Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK plus non-small cell lung cancer (NSCLC): ALTA-1L final results, Publisher: ELSEVIER, Pages: S44-S45, ISSN: 0923-7534
Nastase A, Mandal A, Lu SK, et al., 2022, Integrated genomics point to immune vulnerabilities in pleural mesothelioma (vol 11, 19138, 2021), SCIENTIFIC REPORTS, Vol: 12, ISSN: 2045-2322
O'Sullivan H, MacMahon S, Cui W, et al., 2022, Identification of EGFR exon 20 insertions: next generation sequencing is superior to PCR, Publisher: ELSEVIER IRELAND LTD, Pages: S31-S31, ISSN: 0169-5002
Sherlock S, Zhang YZ, Ly F, et al., 2022, Reducing fixation time significantly reduces failure rates: an audit of failure rates and turn-around times on next generation sequencing (NGS) of non-small lung carcinomas, Publisher: ELSEVIER IRELAND LTD, Pages: S1-S1, ISSN: 0169-5002
Mak K-M, McDonald F, Teague J, et al., 2022, SARON: stereotactic ablative radiotherapy for oligometastatic non-small cell lung cancer (NSCLC), Publisher: ELSEVIER IRELAND LTD, Pages: S71-S71, ISSN: 0169-5002
Popat S, Ramalingam S, Kim TM, et al., 2022, Mobocertinib (TAK-788) in epidermal growth factor receptor gene (EGFR) exon 20 insertion mutation-positive (EGFRex20ins+) metastatic non-small cell lung cancer (mNSCLC): results from the platinum-pretreated patients (PPP) cohort of a phase 1/2 study, Publisher: ELSEVIER IRELAND LTD, Pages: S30-S31, ISSN: 0169-5002
Popat S, Kim HR, Ahn M-J, et al., 2022, Brigatinib vs crizotinib in ALK TKI-naive ALK plus NSCLC: final results from ALTA-1L, Publisher: ELSEVIER IRELAND LTD, Pages: S27-S28, ISSN: 0169-5002
McDonald F, Guckenberger M, Popat S, et al., 2022, HALT: targeted therapy with or without dose-intensified radiotherapy in oligo-progressive disease in oncogene addicted lung tumours, Publisher: ELSEVIER IRELAND LTD, Pages: S70-S71, ISSN: 0169-5002
Griesinger F, Cox O, Sammon C, et al., 2022, Health technology assessments and real-world evidence: tell us what you want, what you really, really want Comment, JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH, Vol: 11, Pages: 297-299, ISSN: 2042-6305
Coleman N, Harbery A, Heuss S, et al., 2022, Targeting un-MET needs in advanced non-small cell lung cancer, LUNG CANCER, Vol: 164, Pages: 56-68, ISSN: 0169-5002
Popat S, Baas P, Faivre-Finn C, et al., 2022, Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, ANNALS OF ONCOLOGY, Vol: 33, Pages: 129-142, ISSN: 0923-7534
Mencel J, Feber A, Begum R, et al., 2022, Liquid biopsy for diagnosis in patients with suspected pancreatic and biliary tract cancers: PREVAIL ctDNA pilot trial, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Cui W, Milner-Watts C, McVeigh TP, et al., 2022, A pilot of Blood-First diagnostic cell free DNA (cfDNA) next generation sequencing (NGS) in patients with suspected advanced lung cancer., Lung Cancer, Vol: 165, Pages: 34-42
INTRODUCTION: The diagnostic pathway for lung cancer can be long. Availability of front-line targeted therapies for NSCLC demands access to good quality tissue for genomic sequencing and rapid reporting of results. Diagnosis of lung cancer and availability of tissue was delayed during the COVID-19 pandemic. METHODS: A pilot study assessing Guardant360™ cfDNA-NGS in patients with radiological-suspected advanced-stage lung cancer was performed at an academic cancer centre during COVID-19. Variants were tiered using AMP/ASCO/CAP guidelines and discussed at a tumour molecular board. The primary endpoint was the proportion of patients who commenced targeted treatment based on cfDNA-NGS results without tissue molecular results, predicted to be ≥ 10%. RESULTS: Between April 2020-May 2021, 51 patients were enrolled; 49 were evaluable. The median age was 71 years, 43% were never-smokers, 86% had stage IV disease. 80% of evaluable cfDNA-NGS were informative (tumour-derived cfDNA detected). cfDNA-NGS detected 30 (61%) AMP/ASCO/CAP tier 1 variants, including 20 additional tier 1 variants compared to tissue testing. Three patients with non-informative cfDNA-NGS had tier 1 variants identified on tissue testing. Eleven (22%; 95%CI 12%-27%) patients commenced targeted therapy based on cfDNA-NGS results without tissue molecular results, meeting the primary endpoint. Median time to results was shorter for cfDNA-NGS compared to standard-of-care tissue tests (9 versus 25 days, P < 0.0001). CONCLUSION: Blood-first cfDNA-NGS in NSCLC patients increased the breadth and rapidity of detection of actionable variants with high tissue concordance and led to timely treatment decisions. A blood-first approach should be considered to improve the speed and accuracy of therapeutic decision-making.
Popat S, Ramagopalan SV, Ray J, et al., 2022, Assessment of tumour-agnostic therapies in basket trials., Lancet Oncol, Vol: 23
Yang JC-H, Schuler M, Popat S, et al., 2022, Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: An Updated Database of 1023 Cases Brief Report., Front Oncol, Vol: 12, ISSN: 2234-943X
Introduction: Previously, we developed a database of 693 patients with NSCLC and uncommon EGFR mutations treated with afatinib. Here, we provide an update of >1000 patients, with more data on specific mutations. Methods: Patients were identified from a prospective database developed by Boehringer Ingelheim and via literature review. Mutations were categorized as T790M-positive, exon 20 insertions, major uncommon (G719X, L861Q, S768I) and 'others'. Patients with compound mutations (≥2 EGFR mutations) were analyzed separately. Key endpoints were time to treatment failure (TTF) and objective response rate (ORR). Results: Of 1023 patients included, 587 patients were EGFR TKI-naïve and 425 were EGFR TKI-pretreated. The distribution of mutation categories was: major uncommon (41.4%); exon 20 insertions (22.3%); T790M (20.3%); and 'others' (15.9%); 38.6% had compound mutations. Overall, median TTF (TKI naïve/pretreated) was 10.7 and 4.5 months. ORR was 49.8% and 26.8%, respectively. In TKI-naïve patients, afatinib demonstrated activity against major uncommon mutations (median TTF: 12.6 months; ORR: 59.0%), 'other' mutations (median TTF: 10.7 months; ORR: 63.9%) including strong activity against E709X (11.4 months; 84.6%) and L747X (14.7 months; 80.0%), and compound mutations (11.5 months; 63.9%). Although sample sizes were small, notable activity was observed against specific exon 20 insertions at residues A763, M766, N771, and V769, and against osimertinib resistance mutations (G724S, L718X, C797S). Conclusion: Afatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, 'other' (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance EGFR mutations.
Fendler A, Shepherd STC, Au L, et al., 2021, Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer., Cancer Cell, ISSN: 1535-6108
Peters S, Pujol J-L, Dafni U, et al., 2021, Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial, ANNALS OF ONCOLOGY, Vol: 33, Pages: 67-79, ISSN: 0923-7534
Girard N, Popat S, Shoshkova S, et al., 2021, IMreal Cohort 2: First interim analysis of patient (pt) characteristics and safety data in pts with locally advanced or metastatic NSCLC (aNSCLC) receiving atezolizumab (atezo) under real-world conditions, ESMO Immuno-Oncology Congres, Publisher: ELSEVIER, Pages: S1418-S1419, ISSN: 0923-7534
Curcean S, Cheng L, Picchia S, et al., 2021, Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations., JTO Clin Res Rep, Vol: 2
INTRODUCTION: We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response. METHODS: Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival. RESULTS: The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment (p = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment (r = -0.560, p = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, p < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival (r = 0.45, p = 0.03). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker.
Camidge DR, Kim HR, Ahn M-J, et al., 2021, Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial, JOURNAL OF THORACIC ONCOLOGY, Vol: 16, Pages: 2091-2108, ISSN: 1556-0864
Au L, Hatipoglu E, de Massy MR, et al., 2021, Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma, CANCER CELL, Vol: 39, Pages: 1497-+, ISSN: 1535-6108
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