First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

New England Journal of Medicine, Год журнала: 2018, Номер 379(23), С. 2220 - 2229

Опубликована: Сен. 25, 2018

Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)–programmed (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.

Язык: Английский

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Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Annals of Oncology, Год журнала: 2018, Номер 29, С. iv192 - iv237

Опубликована: Июль 26, 2018

Primary lung cancer remains the most common malignancy after non-melanocytic skin cancer, and deaths from exceed those any other worldwide [1.IARC. Cancer Incidence, Mortality Prevalence Worldwide GLOBOCAN 2012. http://gco.iarc.fr/Google Scholar]. In 2012, was frequently diagnosed in males with an estimated 1.2 million incident cases worldwide. Among females, leading cause of death more developed countries second less The highest incidence is found Central/Eastern Europe Asia age-standardised rates 53.5 50.4 per 100 000, respectively. European projections for 2017 indicate a 10.7% drop 5 years 33.3/100 000 rise 5.1% 14.6/100 females [2.Malvezzi M. Carioli G. Bertuccio P. et al.European mortality predictions year 2017, focus on cancer.Ann Oncol. 2017; 28: 1117-1123Abstract Full Text PDF PubMed Scopus (153) Google Contrary to United States, rate increasing [3.Jemal A. Ward E.M. Johnson C.J. al.Annual Report Nation Status Cancer, 1975-2014, Featuring Survival.J Natl Inst. 109 (djx 0130)Crossref (592) number cancer-related represent both genders, accounting 24% 15% respectively Non-small cell (NSCLC) accounts 80%–90% cancers, while small (SCLC) has been decreasing frequency many over past two decades [4.Jemal Bray F. Center M.M. al.Global statistics.CA J Clin. 2011; 61: 69-90Crossref (28678) During last 25 years, distribution histological types NSCLC changed: squamous carcinoma (SCC), formerly predominant histotype, decreased, adenocarcinoma increased genders. Europe, similar trends have occurred men, women, SCC are still [5.Forman D. Brewster Incidence Five Continents. IARC Press, Lyon2013Google World Health Organization (WHO) estimates that 1.59 globally year, 71% them caused by smoking. Tobacco smoking main geographical temporal patterns disease largely reflect tobacco consumption during previous decades. Both prevention cessation can lead reduction large fraction cancers [6.Ordonez-Mena J.M. Schottker B. Mons U. al.Quantification smoking-associated risk advancement periods: meta-analysis individual participant data cohorts CHANCES consortium.BMC Med. 2016; 14: 62Crossref active control measures, begun decline men reaching plateau women Scholar, 7.Malvezzi Levi 2013.Ann 2013; 24: 792-800Abstract (275) 8.Jemal Ma J. Rosenberg P.S. al.Increasing among young southern midwestern States.J Clin 2012; 30: 2739-2744Crossref (55) 9.Hashim Boffetta La Vecchia C. al.The global decrease mortality: disparities.Ann 27: 926-933Abstract (177) Several factors described as factors, including exposure asbestos, arsenic, radon non-tobacco-related polycyclic aromatic hydrocarbons. Hypotheses about indoor air pollution (e.g. coal-fuelled stoves cooking fumes) made relatively high burden non-smoking-related some [10.Malhotra Malvezzi Negri E. al.Risk worldwide.Eur Respir 48: 889-902Crossref There evidence higher cities than rural settings but confounding outdoor may be responsible this pattern. About 500 annually attributed lifetime never-smokers Absence history characterises 19% female compared 9% male States [11.Novello S. Stabile L. Siegfried Gender-related Differences Lung Cancer. IASLC Multidisciplinary Approach Thoracic Oncology. Aurora, CO2014Google 12.McCarthy W. Meza R. Jeon Moolgavkar Chapter 6: never smokers: epidemiology prediction models.Risk Anal. 32: S69.Crossref (0) An increase proportion observed, especially Asian [13.Toh C.K. Gao Lim W.T. al.Never-smokers cancer: epidemiologic distinct entity.J 2006; 2245-2251Crossref (271) These new epidemiological resulted ‘non-smoking-associated cancer’ being considered entity, where specific molecular genetic tumour characteristics identified [14.Couraud Souquet P.J. Paris al.BioCAST/IFCT-1002: features never-smokers.Eur 2015; 45: 1403-1414Crossref (40) Use non-cigarette products such cigars pipes increasing. A pooled analysis highlighted risk, particularly head neck smokers (former current) [15.Malhotra Borron Freedman N.D. al.Association between Cigar or pipe men: five Cohort studies.Cancer Prev Res (Phila). 10: 704-709Crossref Familial reported several registry-based studies careful adjustment [16.Lorenzo Bermejo Hemminki K. aggregation habits: simulation effect shared environmental familial cancer.Cancer Epidemiol Biomarkers Prev. 2005; 1738-1740Crossref recent study heritability at 18% components remain unidentified. Genome-wide association (GWAS) susceptibility loci CHRNA3, CHRNA5, TERT, BRCA2, CHECK2 human leukocyte antigen (HLA) region [17.Mucci L.A. Hjelmborg J.B. Harris J.R. al.Familial twins Nordic Countries.JAMA. 315: 68-76Crossref (301) 18.Timofeeva M.N. Hung R.J. Rafnar T. al.Influence variation risk: 14 900 29 485 controls.Hum Mol Genet. 21: 4980-4995Crossref (147) 19.Wang Y. McKay J.D. al.Rare variants BRCA2 CHEK2 affect cancer.Nat 2014; 46: 736-741Crossref (179) Another trial, 266 56 450 controls descent, 18 genome-wide significance, which 10 were previously unknown. Interestingly, four latter associated overall six only [20.McKay Han al.Large-scale identifies heterogeneity across subtypes.Nat 49: 1126-1132Crossref (160) Changes therapeutic scenario 15 emphasised need multidisciplinary approach cancer. Data show high-volume centres teams efficient managing patients low-volume non-multidisciplinary centres, providing complete staging, better adherence guidelines survival [21.Freeman R.K. Van Woerkom Vyverberg Ascioti A.J. thoracic conference treatment cancer.Eur Cardiothorac Surg. 2010; 38: 1-5Crossref (76) 22.Forrest L.M. McMillan D.C. McArdle C.S. Dunlop D.J. evaluation impact team, single centre, inoperable non-small-cell cancer.Br 93: 977-978Crossref (148) boards influence providers’ initial plans 26%–40% [23.Schmidt H.M. Roberts Bodnar A.M. al.Thoracic tumor board routinely impacts esophageal prospective cohort study.Ann Thorac 99: 1719-1724Abstract absolute reach proper precise morphological biological definition often requires challenging tissue sampling, decisions depending information obtained specimen collected diagnosis. Bronchoscopy technique ideally suited large, central lesions offers advantage minimal morbidity. used bronchial washing, brushing, transbronchial biopsy, diagnostic yield 65%–88% [24.Ost D.E. Ernst Lei X. al.Diagnostic complications bronchoscopy peripheral lesions. Results AQuIRE Registry.Am Crit Care 193: 68-77Crossref 25.Rivera M.P. Mehta A.C. Wahidi Establishing diagnosis management 3rd ed: American College Chest Physicians evidence-based clinical practice guidelines.Chest. 143: e142S-e165SAbstract (530) 26.van der Drift M.A. van Wilt G.J. Thunnissen F.B. Janssen J.P. timing cost-effectiveness washing pulmonary malignant tumors.Chest. 128: 394-400Abstract (65) By combining direct bronchoscopic airway visualisation ultrasound-guided biopsy lesion, endobronchial ultrasound (EBUS) provides 75%–85% centrally located [27.Herth Becker H.D. Conventional vs needle aspiration: randomized trial.Chest. 2004; 125: 322-325Abstract (350) 28.Paone Nicastri Lucantoni al.Endobronchial ultrasound-driven lesions.Chest. 3551-3557Abstract (185) Fibre optic allows regional lymph nodes EBUS and/or endoscopic (EUS). EBUS-guided aspiration (TBNA) invasive least accurate mediastinoscopy [29.Adams Shah P.L. Edmonds Test performance mediastinal staging systematic review meta-analysis.Thorax. 2009; 64: 757-762Crossref (291) shown cytological specimens EBUS-TBNA suitable testing epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homologue (KRAS) anaplastic lymphoma kinase (ALK) status [30.Nakajima Kimura H. Takeuchi al.Treatment ALK inhibitor EML4-ALK fusion gene detection using aspiration.J 5: 2041-2043Abstract (21) 31.Nakajima Yasufuku Nakagawara al.Multigene mutation metastatic non-small aspiration.Chest. 140: 1319-1324Abstract (97) 32.Rekhtman N. Brandt S.M. Sigel al.Suitability cytology paradigms carcinoma: accuracy subtyping feasibility EGFR KRAS testing.J 451-458Abstract (200) 33.Sakairi Nakajima al.EML4-ALK assessment node samples aspiration.Clin Res. 16: 4938-4945Crossref (140) Scholar]; however, collection broader should encouraged. case lesions, transthoracic percutaneous fine core under imaging guidance [typically computed tomography (CT)] proposed [34.Chan E.Y. Gaur Ge al.Management solitary nodule.Arch Pathol Lab 141: 927-931Crossref (8) Needle > 88% yield, sensitivity 90% false-negative 22% [25.Rivera 35.Choi S.H. Chae E.J. Kim J.E. al.Percutaneous CT-guided nodules smaller 1 cm: outcomes 305 procedures tertiary referral center.AJR Am Roentgenol. 201: 964-970Crossref 36.Fontaine-Delaruelle Gamondes al.Negative predictive value core-needle biopsy: multicenter study.Chest. 148: 472-480Abstract (36) 37.Lee Park C.M. Lee K.H. al.C-arm cone-beam nodules: experience 1108 patients.Radiology. 271: 291-300Crossref (118) 38.Takeshita Masago Kato al.CT-guided fine-needle biopsies lesions: single-center 750 Japan.AJR 204: 29-34Crossref (43) significant disadvantage procedural pneumothorax, ranging 17% 50% [37.Lee presence pleural effusion, thoracentesis could tool palliative treatment. If fluid examination negative, image-guided surgical thoracoscopy carried out. More invasive, approaches [mediastinoscopy, mediastinotomy, thoracoscopy, video-assisted thorascopic surgery (VATS), secondary lesion resection etc.] workup when techniques cannot allow Histological crucial exact detailed available technology allow. Diagnosis based upon criteria laid out WHO classification [39.Travis W.D. Brambilla Burke A.P. al.WHO Classification Tumours Lung, Pleura, Thymus Heart.4th edition. Lyon, France2015Google This details surgically resected tumours but, importantly, also assessing reporting not met 40.Travis Noguchi al.Diagnosis cytology: implications 2011 International Association Study Cancer/American Society/European Respiratory Society classification.Arch 137: 668-684Crossref (251) 41.Travis al.International cancer/american society/european respiratory society international adenocarcinoma.J 244-285Abstract (3131) Most present advanced stage unresectable disease, therefore all treatment-determining diagnoses must cytology-type samples. Sampling primary accessible metastases, taken vision usually assistance, greatly increases (hit rate). facilitate well limited material handled accordingly; ensuring processing likely sparingly each step, since tests required [42.Dietel Bubendorf Dingemans (NSCLC): recommendations Expert Group.Thorax. 71: 177-184Crossref (89) Immunohistochemistry (IHC) become key biomarker assessment. possible morphology alone, panel IHC recommended determine subtype Thyroid transcription (TTF1) positivity probable adenocarcinoma, p40 SCC; if neither positive NSCLC-not otherwise specified (NOS). staining reduce NSCLC-NOS < 10% [IV, A]. Pathologists urged conserve every diagnosis, use sections avoid excessive investigation, clinically relevant. After next consideration therapy-predictive testing. will driven availability treatments vary widely different geopolitical health systems [43.Lindeman N.I. Cagle P.T. Beasley M.B. al.Molecular guideline selection tyrosine inhibitors: Pathologists, Molecular Pathology.J 8: 823-859Abstract (588) 44.Kerr K.M. Edelman M.J. al.Second ESMO consensus pathology biomarkers 25: 1681-1690Abstract (191) 45.Lindeman Aisner al.Updated targeted Pathology.Arch 2018; 142: 321-346Crossref (257) Contemporary now evolved into streams, one targetable, addictive, oncogenic alterations immuno-oncology therapy personalised medicine synopsis table Table 1.Table 1A NSCLCBiomarkerMethodUseLoE, GoREGFR mutationAny appropriate, validated method, subject external quality assuranceTo select EGFR-sensitising mutations respond TKI therapyI, AALK rearrangementAny assurance. FISH historical standard becoming therapy-determining test, provided method against orthogonal test approach. NGS emerging technologyTo rearrangements AROS1 rearrangementFISH trial-validated standard. confirmatory currently lacks specificity. technology. External assurance essentialTo ROS1 therapyII, ABRAF BRAF V600-sensitising inhibitor, without MEK APD-L1 expressionIHC identify PD-L1 expression appropriate level population(s) determined intended drug line therapy. Only trial assays validated. Internal enrich benefit anti-PD-1 anti-PD-L1 For pembrolizumab, companion nivolumab atezolizumab, complementaryI, AALK, kinase; EGFR, receptor; FISH, fluorescent situ hybridisation; GoR, grade recommendation; IHC, immunohistochemistry; LoE, evidence; MEK, mitogen-activated protein NGS, next-generation sequencing; NSCLC, cancer; PD-1, programmed 1; PD-L1, death-ligand TKI, inhibitor. Open tab ALK, drivers addiction strong excellent targets. They generally mutually exclusive much never- (never smoked who cigarettes lifetime), long-time ex- (> years) light-smokers (< pack-years) they smoke. vast majority oncogene-addicted adenocarcinomas. Patients, general, tend younger, gender East ethnicity enriches EGFR-mutant tumours. Nonetheless, suggest advanced, possible, definite, tested 46.Kalemkerian G.P. Narula Kennedy E.B. Clinical Oncology Endorsement Pathologists/International Cancer/Association Pathology Practice Guideline Update.J 36: 911-919PubMed SCC, except rare circumstances never-, light-smoker Testing involving genes mandatory countries. V600E rapidly approaching first-line BRAF/MEK inhibitors approved, HER2 (human 2) MET exon RET NTRK1 (neurotropic tropomyosin 1) evolving targets/biomarkers

Язык: Английский

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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy

Nature reviews. Cancer, Год журнала: 2019, Номер 19(3), С. 133 - 150

Опубликована: Фев. 12, 2019

Язык: Английский

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Top 10 Challenges in Cancer Immunotherapy

Immunity, Год журнала: 2020, Номер 52(1), С. 17 - 35

Опубликована: Янв. 1, 2020

Язык: Английский

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Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC

New England Journal of Medicine, Год журнала: 2020, Номер 383(14), С. 1328 - 1339

Опубликована: Сен. 30, 2020

The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those platinum-based chemotherapy, first-line treatment for patients metastatic non-small-cell lung cancer (NSCLC) PD-L1 expression are not known.We conducted a randomized, open-label, phase 3 trial involving nonsquamous or squamous NSCLC who had previously received chemotherapy on at least 1% tumor cells tumor-infiltrating immune assessed by SP142 immunohistochemical assay. Patients were assigned in 1:1 ratio to receive atezolizumab chemotherapy. Overall survival (primary end point) was tested hierarchically according status among intention-to-treat population whose tumors wild-type respect EGFR mutations ALK translocations. Within tumors, overall progression-free also prospectively subgroups defined findings two assays well blood-based mutational burden.Overall, 572 enrolled. In subgroup highest (205 patients), median longer 7.1 months group than (20.2 vs. 13.1 months; hazard death, 0.59; P = 0.01). Among all could be evaluated safety, adverse events occurred 90.2% 94.7% group; grade 4 30.1% 52.5% respective groups. favored high burden.Atezolizumab resulted significantly expression, regardless histologic type. (Funded F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).

Язык: Английский

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Current and future perspectives of liquid biopsies in genomics-driven oncology

Nature Reviews Genetics, Год журнала: 2018, Номер 20(2), С. 71 - 88

Опубликована: Ноя. 8, 2018

Язык: Английский

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PD-L1 as a biomarker of response to immune-checkpoint inhibitors

Nature Reviews Clinical Oncology, Год журнала: 2021, Номер 18(6), С. 345 - 362

Опубликована: Фев. 12, 2021

Язык: Английский

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The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker

Cancer Cell, Год журнала: 2020, Номер 39(2), С. 154 - 173

Опубликована: Окт. 30, 2020

Язык: Английский

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Molecular profiling for precision cancer therapies

Genome Medicine, Год журнала: 2020, Номер 12(1)

Опубликована: Янв. 14, 2020

Abstract The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies several cancer types. Molecular pathology therefore become fundamental not only to inform on tumor diagnosis and prognosis but also drive therapeutic decisions daily practice. introduction next-generation sequencing technologies rising large-scale profiling programs across institutions worldwide have revolutionized field precision oncology. As comprehensive genomic analyses increasingly available both clinical research settings, healthcare professionals are faced complex tasks result interpretation translation. This review summarizes current upcoming approaches implement medicine, highlighting challenges potential solutions facilitate maximize utility results. We describe novel characterization strategies beyond DNA sequencing, such as transcriptomics, immunophenotyping, epigenetic profiling, single-cell analyses. applications liquid biopsies evaluate blood-based biomarkers, circulating cells nucleic acids. Last, lessons learned existing limitations genotype-derived provide insights into ways expand medicine genomics.

Язык: Английский

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Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors

Cancer Discovery, Год журнала: 2020, Номер 10(12), С. 1808 - 1825

Опубликована: Ноя. 3, 2020

Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase interrogated genomic sequence, varies across malignancies. Panel sequencing-based estimates TMB have largely replaced whole-exome sequencing-derived in clinic. Retrospective evidence suggests that can predict efficacy immune checkpoint inhibitors, and data from KEYNOTE-158 led to recent FDA approval pembrolizumab for TMB-high tumor subgroup. Unmet needs include prospective validation cutoffs relationship type patient outcomes. Furthermore, standardization harmonization measurement test platforms are important successful implementation clinical practice. SIGNIFICANCE: Evaluation a predictive biomarker creates need harmonize panel-based estimation standardize its reporting. improve accuracy immunotherapy outcomes, has potential expand candidate pool patients treatment with inhibitors.

Язык: Английский

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