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Advanced Lung Non-Squamous Non-Small Cell Carcinoma

MedGen UID:
1644529
•Concept ID:
C4688308
•
Neoplastic Process
Synonym: Advanced Non-Squamous Non-Small Cell Lung Carcinoma

Definition

Non-squamous non-small cell lung carcinoma that has spread extensively to other anatomic sites or is no longer responding to treatment. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAdvanced Lung Non-Squamous Non-Small Cell Carcinoma

Professional guidelines

PubMed

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials.
Daei Sorkhabi A, ZareDini M, Fazlollahi A, Sarkesh A, Naseri A, Mousavi SE, Nejadghaderi SA, Sullman MJM, Kolahi AA, Safiri S
BMC Pulm Med 2023 Dec 8;23(1):495. doi: 10.1186/s12890-023-02755-3. PMID: 38066549Free PMC Article
Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.
Dafni U, Tsourti Z, Vervita K, Peters S
Lung Cancer 2019 Aug;134:127-140. Epub 2019 May 30 doi: 10.1016/j.lungcan.2019.05.029. PMID: 31319971
Management of non-small cell lung cancer in the era of personalized medicine.
Rocco G, Morabito A, Leone A, Muto P, Fiore F, Budillon A
Int J Biochem Cell Biol 2016 Sep;78:173-179. Epub 2016 Jul 15 doi: 10.1016/j.biocel.2016.07.011. PMID: 27425397

Recent clinical studies

Etiology

Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial.
Lu S, Wu L, Jian H, Cheng Y, Wang Q, Fang J, Wang Z, Hu Y, Han L, Sun M, Miao L, Ding C, Cui J, Wang K, Li B, Li X, Ye F, Liu A, Pan Y, Cang S, Zhou H, Sun X, Shen Y, Wang S, Zhang W, He Y
Lancet Respir Med 2023 Jul;11(7):624-636. Epub 2023 May 5 doi: 10.1016/S2213-2600(23)00135-2. PMID: 37156249
Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial.
Lu S, Wu L, Jian H, Chen Y, Wang Q, Fang J, Wang Z, Hu Y, Sun M, Han L, Miao L, Ding C, Cui J, Li B, Pan Y, Li X, Ye F, Liu A, Wang K, Cang S, Zhou H, Sun X, Ferry D, Lin Y, Wang S, Zhang W, Zhang C
Lancet Oncol 2022 Sep;23(9):1167-1179. Epub 2022 Jul 28 doi: 10.1016/S1470-2045(22)00382-5. PMID: 35908558
Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.
Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, Wagle N, Stenzinger A, Bonastre J, Bayle A, Michiels S, Bièche I, Rouleau E, Jezdic S, Douillard JY, Reis-Filho JS, Dienstmann R, André F
Ann Oncol 2020 Nov;31(11):1491-1505. Epub 2020 Aug 24 doi: 10.1016/j.annonc.2020.07.014. PMID: 32853681
Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.
Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators
Lancet 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4 doi: 10.1016/S0140-6736(18)32409-7. PMID: 30955977
Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.
Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L; KEYNOTE-021 investigators
Lancet Oncol 2016 Nov;17(11):1497-1508. Epub 2016 Oct 10 doi: 10.1016/S1470-2045(16)30498-3. PMID: 27745820Free PMC Article

Diagnosis

Fusion-positive non-small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications.
Kazdal D, Hofman V, Christopoulos P, Ilié M, Stenzinger A, Hofman P
Genes Chromosomes Cancer 2022 May;61(5):244-260. Epub 2022 Jan 22 doi: 10.1002/gcc.23022. PMID: 34997651
Defining comprehensive biomarker-related testing and treatment practices for advanced non-small-cell lung cancer: Results of a survey of U.S. oncologists.
Mileham KF, Schenkel C, Bruinooge SS, Freeman-Daily J, Basu Roy U, Moore A, Smith RA, Garrett-Mayer E, Rosenthal L, Garon EB, Johnson BE, Osarogiagbon RU, Jalal S, Virani S, Weber Redman M, Silvestri GA
Cancer Med 2022 Jan;11(2):530-538. Epub 2021 Dec 17 doi: 10.1002/cam4.4459. PMID: 34921524Free PMC Article
First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.
Greenhalgh J, Boland A, Bates V, Vecchio F, Dundar Y, Chaplin M, Green JA
Cochrane Database Syst Rev 2021 Mar 18;3(3):CD010383. doi: 10.1002/14651858.CD010383.pub3. PMID: 33734432Free PMC Article
First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.
Greenhalgh J, Dwan K, Boland A, Bates V, Vecchio F, Dundar Y, Jain P, Green JA
Cochrane Database Syst Rev 2016 May 25;(5):CD010383. doi: 10.1002/14651858.CD010383.pub2. PMID: 27223332
ALK inhibitors and advanced non-small cell lung cancer (review).
Rossi A, Maione P, Sacco PC, Sgambato A, Casaluce F, Ferrara ML, Palazzolo G, Ciardiello F, Gridelli C
Int J Oncol 2014 Aug;45(2):499-508. Epub 2014 May 29 doi: 10.3892/ijo.2014.2475. PMID: 24889366

Therapy

Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer.
Awad MM, Govindan R, Balogh KN, Spigel DR, Garon EB, Bushway ME, Poran A, Sheen JH, Kohler V, Esaulova E, Srouji J, Ramesh S, Vyasamneni R, Karki B, Sciuto TE, Sethi H, Dong JZ, Moles MA, Manson K, Rooney MS, Khondker ZS, DeMario M, Gaynor RB, Srinivasan L
Cancer Cell 2022 Sep 12;40(9):1010-1026.e11. Epub 2022 Aug 25 doi: 10.1016/j.ccell.2022.08.003. PMID: 36027916
Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.
Gogishvili M, Melkadze T, Makharadze T, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Li S, McGuire K, Kaul M, Paccaly A, Quek RGW, Gao B, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Gullo G, Rietschel P
Nat Med 2022 Nov;28(11):2374-2380. Epub 2022 Aug 25 doi: 10.1038/s41591-022-01977-y. PMID: 36008722Free PMC Article
Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial.
Lu S, Wu L, Jian H, Chen Y, Wang Q, Fang J, Wang Z, Hu Y, Sun M, Han L, Miao L, Ding C, Cui J, Li B, Pan Y, Li X, Ye F, Liu A, Wang K, Cang S, Zhou H, Sun X, Ferry D, Lin Y, Wang S, Zhang W, Zhang C
Lancet Oncol 2022 Sep;23(9):1167-1179. Epub 2022 Jul 28 doi: 10.1016/S1470-2045(22)00382-5. PMID: 35908558
Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.
Lu S, Wang J, Yu Y, Yu X, Hu Y, Ai X, Ma Z, Li X, Zhuang W, Liu Y, Li W, Cui J, Wang D, Liao W, Zhou J, Wang Z, Sun Y, Qiu X, Gao J, Bao Y, Liang L, Wang M
J Thorac Oncol 2021 Sep;16(9):1512-1522. Epub 2021 May 23 doi: 10.1016/j.jtho.2021.05.005. PMID: 34033975
Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.
Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L; KEYNOTE-021 investigators
Lancet Oncol 2016 Nov;17(11):1497-1508. Epub 2016 Oct 10 doi: 10.1016/S1470-2045(16)30498-3. PMID: 27745820Free PMC Article

Prognosis

KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing.
Lim TKH, Skoulidis F, Kerr KM, Ahn MJ, Kapp JR, Soares FA, Yatabe Y
Lung Cancer 2023 Oct;184:107293. Epub 2023 Jul 13 doi: 10.1016/j.lungcan.2023.107293. PMID: 37683526
First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial.
Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, Nechaeva M, Schenker M, Cicin I, Ho GF, Kulyaba Y, Zyuhal K, Scheusan RI, Garassino MC, He X, Kaul M, Okoye E, Li Y, Li S, Pouliot JF, Seebach F, Lowy I, Gullo G, Rietschel P
Lancet Oncol 2023 Sep;24(9):989-1001. Epub 2023 Aug 14 doi: 10.1016/S1470-2045(23)00329-7. PMID: 37591293
Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.
Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, Wagle N, Stenzinger A, Bonastre J, Bayle A, Michiels S, Bièche I, Rouleau E, Jezdic S, Douillard JY, Reis-Filho JS, Dienstmann R, André F
Ann Oncol 2020 Nov;31(11):1491-1505. Epub 2020 Aug 24 doi: 10.1016/j.annonc.2020.07.014. PMID: 32853681
Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.
Dafni U, Tsourti Z, Vervita K, Peters S
Lung Cancer 2019 Aug;134:127-140. Epub 2019 May 30 doi: 10.1016/j.lungcan.2019.05.029. PMID: 31319971
Genetic mutation screen in early non--small-cell lung cancer (NSCLC) specimens.
Bar J, Damianovich M, Hout Siloni G, Dar E, Cohen Y, Perelman M, Ben Nun A, Simansky D, Yellin A, Urban D, Onn A
Clin Lung Cancer 2014 Mar;15(2):159-65. Epub 2013 Nov 14 doi: 10.1016/j.cllc.2013.11.005. PMID: 24370118

Clinical prediction guides

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial.
Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, Nechaeva M, Schenker M, Cicin I, Ho GF, Kulyaba Y, Zyuhal K, Scheusan RI, Garassino MC, He X, Kaul M, Okoye E, Li Y, Li S, Pouliot JF, Seebach F, Lowy I, Gullo G, Rietschel P
Lancet Oncol 2023 Sep;24(9):989-1001. Epub 2023 Aug 14 doi: 10.1016/S1470-2045(23)00329-7. PMID: 37591293
Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer.
Awad MM, Govindan R, Balogh KN, Spigel DR, Garon EB, Bushway ME, Poran A, Sheen JH, Kohler V, Esaulova E, Srouji J, Ramesh S, Vyasamneni R, Karki B, Sciuto TE, Sethi H, Dong JZ, Moles MA, Manson K, Rooney MS, Khondker ZS, DeMario M, Gaynor RB, Srinivasan L
Cancer Cell 2022 Sep 12;40(9):1010-1026.e11. Epub 2022 Aug 25 doi: 10.1016/j.ccell.2022.08.003. PMID: 36027916
Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.
Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, Wagle N, Stenzinger A, Bonastre J, Bayle A, Michiels S, Bièche I, Rouleau E, Jezdic S, Douillard JY, Reis-Filho JS, Dienstmann R, André F
Ann Oncol 2020 Nov;31(11):1491-1505. Epub 2020 Aug 24 doi: 10.1016/j.annonc.2020.07.014. PMID: 32853681
Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.
Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators
Lancet 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4 doi: 10.1016/S0140-6736(18)32409-7. PMID: 30955977
Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.
Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L; KEYNOTE-021 investigators
Lancet Oncol 2016 Nov;17(11):1497-1508. Epub 2016 Oct 10 doi: 10.1016/S1470-2045(16)30498-3. PMID: 27745820Free PMC Article

Recent systematic reviews

Long-term comparative efficacy and safety of nivolumab plus ipilimumab relative to other first-line therapies for advanced non-small-cell lung cancer: A systematic literature review and network meta-analysis.
O'Byrne K, Popoff E, Badin F, Lee A, Yuan Y, Lozano-Ortega G, Eccles LJ, Varol N, Waser N, Penrod JR, Goring S
Lung Cancer 2023 Mar;177:11-20. Epub 2023 Jan 11 doi: 10.1016/j.lungcan.2023.01.006. PMID: 36669321
A systematic review and network meta-analysis of first-line immune checkpoint inhibitor combination therapies in patients with advanced non-squamous non-small cell lung cancer.
Shao T, Zhao M, Liang L, Tang W
Front Immunol 2022;13:948597. Epub 2022 Oct 26 doi: 10.3389/fimmu.2022.948597. PMID: 36389713Free PMC Article
First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.
Greenhalgh J, Boland A, Bates V, Vecchio F, Dundar Y, Chaplin M, Green JA
Cochrane Database Syst Rev 2021 Mar 18;3(3):CD010383. doi: 10.1002/14651858.CD010383.pub3. PMID: 33734432Free PMC Article
Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.
Dafni U, Tsourti Z, Vervita K, Peters S
Lung Cancer 2019 Aug;134:127-140. Epub 2019 May 30 doi: 10.1016/j.lungcan.2019.05.029. PMID: 31319971
First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.
Greenhalgh J, Dwan K, Boland A, Bates V, Vecchio F, Dundar Y, Jain P, Green JA
Cochrane Database Syst Rev 2016 May 25;(5):CD010383. doi: 10.1002/14651858.CD010383.pub2. PMID: 27223332

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