Identification of drug combinations for lung cancer patients whose tumors are unresponsive to targeted therapy: clinical bases and future directions

References

• Torti D, Trusolino L. Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Mol Med. 2011;3(11):623–636.
   PubMed Web of Science ®Google Scholar
• Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458(7239):719–724.
   PubMed Web of Science ®Google Scholar
• Heist RS, Sequist LV, Engelman JA. Genetic changes in squamous cell lung cancer: a review. J Thorac Oncol. 2012;7(5):924–933.
   PubMed Web of Science ®Google Scholar
• Fois SS, Paliogiannis P, Zinellu A, et al. Molecular epidemiology of the main druggable genetic alterations in non-small cell lung cancer. Int J Mol Sci. 2021;22(2):612.
   PubMed Web of Science ®Google Scholar
• Ramlau R, Cufer T, Berzinec P, et al. INSIGHT study team. epidermal growth factor receptor mutation-positive non-small-cell lung cancer in the real-world setting in central Europe: The INSIGHT study. J Thorac Oncol. 2015Sep;10(9):1370–1374. PMID: 26291014
   PubMed Web of Science ®Google Scholar
• Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985–78993.
   PubMedGoogle Scholar
• Hofman P. ALK in non-small cell lung cancer (NSCLC) pathobiology, epidemiology, detection from tumor tissue and algorithm diagnosis in a daily practice. Cancers (Basel). 2017;9(8):107.
   PubMed Web of Science ®Google Scholar
• Chia PL, Mitchell P, Dobrovic A, et al. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol. 2014;6:423–432. Published 2014 Nov 20.
   PubMed Web of Science ®Google Scholar
• Mehta A, Saifi M, Batra U, et al. Incidence of ROS1-rearranged non-small-cell lung carcinoma in India and efficacy of crizotinib in lung adenocarcinoma patients. Lung Cancer (Auckl). 2020;11:19–25. Published 2020 Feb 24.
   PubMed Web of Science ®Google Scholar
• O’Leary CG, Andelkovic V, Ladwa R, et al. Targeting BRAF mutations in non-small cell lung cancer. Transl Lung Cancer Res. 2019;8(6):1119–1124.
   PubMed Web of Science ®Google Scholar
• Anguera G, Majem M. BRAF inhibitors in advanced non-small cell lung cancer. J Thorac Dis. 2018;10(2):589–592.
   PubMed Web of Science ®Google Scholar
• Luk PP, Yu B, Ng CC, et al. BRAF mutations in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):142–148.
   PubMedGoogle Scholar
• Le T, Gerber DE. ALK alterations and inhibition in lung cancer. Semin Cancer Biol. 2017;42:81–88.
   PubMed Web of Science ®Google Scholar
• da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer. Annu Rev Pathol. 2011;6:49–69. PMID: 20887192.
   PubMed Web of Science ®Google Scholar
• He Y, Sheng W, Hu W, et al. Different types of ROS1 fusion partners yield comparable efficacy to crizotinib. Oncol Res. 2019;27(8):901–910.
   PubMed Web of Science ®Google Scholar
• Li Z, Shen L, Ding D, et al. Efficacy of crizotinib among different types of ROS1 fusion partners in patients with ROS1-rearranged non-small cell lung cancer. J Thorac Oncol. 2018Jul;13(7):987–995. Epub 2018 Apr 25. PMID: 29704675
   PubMed Web of Science ®Google Scholar
• Farago AF, Azzoli CG. Beyond ALK and ROS1: RET, NTRK, EGFR and BRAF gene rearrangements in non-small cell lung cancer. Transl Lung Cancer Res. 2017;6(5):550–559.
   PubMed Web of Science ®Google Scholar
• Haratake N, Seto T. NTRK fusion-positive non-small-cell lung cancer: The diagnosis and targeted therapy. Clin Lung Cancer. 2021Jan;22(1):1–5. Epub 2020 Oct 24. PMID: 33272813.
   PubMed Web of Science ®Google Scholar
• Hsiao SJ, Zehir A, Sireci AN, et al. Detection of tumor NTRK gene fusions to identify patients who may benefit from tyrosine kinase (TRK) inhibitor therapy. J Mol Diagn. 2019;21(4):553–571.
   PubMed Web of Science ®Google Scholar
• Farago AF, Taylor MS, Doebele RC, et al. Clinicopathologic features of non–small-cell lung cancer harboring an NTRK gene fusion JCO precis oncol. 2018;2:O.18.00037.
   Google Scholar
• Bronte G, Ulivi P, Verlicchi A, et al. Targeting RET-rearranged non-small-cell lung cancer: future prospects. Lung Cancer (Auckl). 2019;10:27–36. Published 2019 Mar 20.
   PubMed Web of Science ®Google Scholar
• Drusbosky LM, Rodriguez E, Dawar R, et al. Therapeutic strategies in RET gene rearranged non-small cell lung cancer. J Hematol Oncol. 2021;14(1):50.
   PubMed Web of Science ®Google Scholar
• Adderley H, Blackhall FH, Lindsay CR. KRAS-mutant non-small cell lung cancer: converging small molecules and immune checkpoint inhibition. EBioMedicine. 2019;41:711–716.
   PubMed Web of Science ®Google Scholar
• Zhou W, Christiani DC. East meets West: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and caucasians. Chin J Cancer. 2011;30(5):287–292.
   PubMedGoogle Scholar
• Gou LY, Wu YL. Prevalence of driver mutations in non-small-cell lung cancers in the people’s republic of China. Lung Cancer (Auckl). 2014 Published 2014 Feb 12;5:1–9.
   PubMedGoogle Scholar
• Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type. N Engl J Med. 2021 Jan 14;384(2):185–187. PMID: 33497555.
   PubMed Web of Science ®Google Scholar
• Solassol I, Pinguet F, Quantin X. FDA- and EMA-Approved tyrosine kinase inhibitors in advanced EGFR-Mutated non-small cell lung cancer: safety, tolerability, plasma concentration monitoring, and management. Biomolecules. 2019;9(11):668.
   PubMed Web of Science ®Google Scholar
• Chen R, Manochakian R, James L, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58.
   PubMed Web of Science ®Google Scholar
• Planchard D, Popat S, Kerr K, et al. Advanced non-small cell lung cancer: ESMOClinical practice guidelines for diagnosis, treatment and follow-up annals of oncology 29. 2018 accessed Jul 2021;(Supplement 4):iv192–iv237. Updated version published 15September 2020bythe ESMO Guidelines Committee available at. https://www.esmo.org/content/download/347819/6934778/1/ESMO-CPG-mNSCLC-15SEPT2020.pdf;
   Google Scholar
• NCCN Clinical Practice Guidelines in Oncology Non-Small Cell Lung Cancer; NCCN.org [internet]. Available at: Accessed July 2021. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
   Google Scholar
• Hanna NH, Robinson AG, Temin S, et al. Therapy for stage IV non–small-cell lung cancer with driver alterations: ASCO and OH (CCO. Joint Guideline Update Journal of Clinical Oncology. 2021;39(9):1040–1091.
   PubMed Web of Science ®Google Scholar
• Mok TS, Y-l W, Ahn M-J, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-Positive lung cancer. N Engl J Med. 2017;376(7):629–640.
   PubMed Web of Science ®Google Scholar
• Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR -mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113–125.
   PubMed Web of Science ®Google Scholar
• Ramalingam SS, Vansteenkiste J, Planchard, et al. Overall survival with osimertinib in untreated, EGFR-Mutated advanced NSCLC January 2, 2020. N Engl J Med. 2020;382:41–50.
   PubMed Web of Science ®Google Scholar
• Zhang T, Wan B, Zhao Y, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Transl Lung Cancer Res. 2019;8(3):302–316.
   PubMed Web of Science ®Google Scholar
• FDA broadens afatinib indication to previously untreated, metastatic NSCLC with other non-resistant EGFR mutations; fda.gov [internet]. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-broadens-afatinib-indication-previously-untreated-metastatic-nsclc-other-non-resistant-egfr. Accessed January 2022
   Google Scholar
• Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017 Aug 31;377(9):829–838. Epub 2017 Jun 6. PMID: 28586279.
   PubMed Web of Science ®Google Scholar
• Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020Aug;31(8):1056–1064. Epub 2020 May 11. PMID: 32418886
   PubMed Web of Science ®Google Scholar
• Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in advanced alk inhibitor-naive alk-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020 Nov 1;38(31):3592–3603. Epub 2020 Aug 11. PMID: 32780660; PMCID: PMC7605398.
   PubMed Web of Science ®Google Scholar
• Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018Nov22;379(21):2027–2039. Epub 2018 Sep 25. PMID: 30280657.
   PubMed Web of Science ®Google Scholar
• Planchard D, Smit EF, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant advanced non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017Oct;18(10):1307–1316. Epub 2017 Sep 11. PMID: 28919011
   PubMed Web of Science ®Google Scholar
• Planchard D, Besse B, Groen H, et al. Updated overall survival (OS) and genomic analysis from a single-arm phase II study of dabrafenib (D) + trametinib (T) in patients (pts) with BRAF V600E mutant (Mut) advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2020;38: 15_suppl, 9593.
   Google Scholar
• Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014;371(21):1963–1971.
   PubMed Web of Science ®Google Scholar
• Shaw AT, Riely GJ, Bang YJ, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019;30(7):1121–1126.
   PubMed Web of Science ®Google Scholar
• Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med. 2020;383(9):813–824.
   PubMed Web of Science ®Google Scholar
• Gainor JF, Curigliano G, Kim DW, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021 Jul;22(7):959–969. Epub 2021 Jun 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. PMID: 34118197
   PubMed Web of Science ®Google Scholar
• Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731–739.
   PubMed Web of Science ®Google Scholar
• Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials [published correction appears in lancet Oncol. Lancet Oncol. 2020 Feb;21(2):e70]. [published correction appears in Lancet Oncol. 2020 Jul;21(7):e341] [published correction appears in Lancet Oncol. 2020 Aug;21(8):e372]. 2020;21(2):271-282
   Web of Science ®Google Scholar
• Wolf J, Seto T, Han JY, et al. GEOMETRY mono-1 investigators. Capmatinib in MET exon 14-Mutated or MET-Amplified non-small-cell lung cancer. N Engl J Med. 2020Sep3;383(10):944–957. PMID: 32877583.
   PubMed Web of Science ®Google Scholar
• Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med. 2020;383(10):931–943.
   PubMed Web of Science ®Google Scholar
• Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021 Jun 24;384(25):2371–2381. Epub 2021 Jun 4. PMID: 34096690.
   PubMed Web of Science ®Google Scholar
• Li B, Skoulidis F, Falchook G, et al. PS01.07 registrational phase 2 trial of sotorasib in KRAS p.G12C mutant NSCLC: first Disclosure of the Codebreak 100 primary analysis JTO. 2021 Mar 01;16(3):S61.
   Google Scholar
• Reck M, Carbone DP, Garassino M, et al. Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches. Ann Oncol. 2021Sep;32(9):1101–1110. Epub 2021 Jun 2. PMID: 34089836
   PubMed Web of Science ®Google Scholar
• Salgia R, Pharaon R, Mambetsariev I, et al. The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). Cell Rep Med. 2021;2(1):100186.
   PubMedGoogle Scholar
• Jänne PA, Rybkin II, Spira AI, et al. KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in advanced/ metastatic non–small-cell lung cancer (NSCLC. Harboring KRAS G12C Mutation EJC. 2020 Oct 01;138(SUPPLEMENT 2):S1–S2.
   Google Scholar
• Riely G, Ou SI, Rybkin I, et al. 99O_PR - KRYSTAL-1: activity and preliminary pharmacodynamic (PD) analysis of adagrasib (MRTX849) in patients (Pts) with advanced non-small- cell lung cancer (NSCLC) harboring KRASG12C. Mutation Journal of Thoracic Oncology. 2021;16(suppl_4):S748–S802.
   Web of Science ®Google Scholar
• Rocco D, Battiloro C, Gravara LD, et al. Advanced non-small cell lung cancer with activating epidermal growth factor receptor mutation: First line treatment and beyond. Rev Recent Clin Trials. 2019;14(2):120–128. PMID: 30520383.
   PubMed Web of Science ®Google Scholar
• Pérol M, Pavlakis N, Levchenko E, et al. Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. Lung Cancer. 2019 Dec;138:79–87. Epub 2019 Oct 11. PMID: 31654838.
   PubMed Web of Science ®Google Scholar
• Kim C, Liu SV. First-line EGFR TKI therapy in non-small-cell lung cancer: looking back before leaping forward. Ann Oncol. 2019Dec1;30(12):1852–1855. PMID: 31613313.
   PubMed Web of Science ®Google Scholar
• Zhu Q, Hu H, Weng DS, et al. Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC. BMC Cancer. 2017;17(1):412.
   PubMed Web of Science ®Google Scholar
• Bebb DG, Agulnik J, Albadine R, et al. Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective. Curr Oncol. 2019;26(4):e551–e557.
   PubMed Web of Science ®Google Scholar
• Garcia Campelo MR, Lin HM, Zhu Y, et al. Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor-naive ALK + non-small cell lung cancer (ALTA-1L). Lung Cancer. 2021 May;155:68–77. Epub 2021 Mar 9. PMID: 33744781.
   PubMed Web of Science ®Google Scholar
• Ramirez RA, Lu J, Thomas KEH. Quality of life for non-small cell lung cancer patients in the age of immunotherapy. Transl Lung Cancer Res. 2018;7(Suppl 2):S149–S152.
   PubMed Web of Science ®Google Scholar
• Reck M, Rodríguez-Abreu D, Robinson AG, et al. KEYNOTE-024 investigators. Pembrolizumab versus chemotherapy for PD-L1-Positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823–1833. Epub 2016 Oct 8. PMID: 27718847.
   PubMed Web of Science ®Google Scholar
• Reck M, Rodríguez-Abreu D, Robinson AG, et al. Updated Analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537–546. Epub 2019 Jan 8. PMID: 30620668.
   PubMed Web of Science ®Google Scholar
• Mok TSK, Wu YL, Kudaba I, et al. KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or advanced non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819–1830. Epub 2019 Apr 4. PMID: 30955977.
   PubMed Web of Science ®Google Scholar
• Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198–211. Epub 2021 Jan 18. Erratum in: Lancet Oncol. 2021 Mar;22(3):e92. PMID: 33476593
   PubMed Web of Science ®Google Scholar
• Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019 Nov 21;381(21):2020–2031. Epub 2019 Sep 28. PMID: 31562796.
   PubMed Web of Science ®Google Scholar
• Socinski MA, Jotte RM, Cappuzzo F, et al. IMpower150 Study Group. Atezolizumab for first-line treatment of advanced nonsquamous NSCLC. N Engl J Med. 2018 Jun 14;378(24):2288–2301. Epub 2018 Jun 4. PMID: 29863955.
   PubMed Web of Science ®Google Scholar
• Reck M, Mok TSK, Nishio M, et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019May;7(5):387–401. Epub 2019 Mar 25. PMID: 30922878
   PubMed Web of Science ®Google Scholar
• West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for advanced non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019Jul;20(7):924–937. Epub 2019 May 20. PMID: 31122901
   PubMed Web of Science ®Google Scholar
• Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018Nov22;379(21):2040–2051. Epub 2018 Sep 25. PMID: 30280635.
   PubMed Web of Science ®Google Scholar
• Paz-Ares L, Vicente D, Tafreshi A, et al. A randomized, placebo-controlled trial of pembrolizumab plus chemotherapy in patients with advanced squamous NSCLC: protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020Oct;15(10):1657–1669. Epub 2020 Jun 26. PMID: 32599071
   PubMed Web of Science ®Google Scholar
• Gadgeel S, Rodríguez-Abreu D, Speranza G, et al. Updated analysis from KEYNOTE-189: Pembrolizumab or placebo plus pemetrexed and platinum for previously untreated advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2020 May 10;38(14):1505–1517. Epub 2020 Mar 9. PMID: 32150489.
   PubMed Web of Science ®Google Scholar
• Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078–2092. Epub 2018 Apr 16. PMID: 29658856.
   PubMed Web of Science ®Google Scholar
• Rocco D, Gravara LD, Gridelli C. The new immunotherapy combinations in the treatment of advanced non-small cell lung cancer: reality and perspectives. Curr Clin Pharmacol. 2020;15(1):11–19.
   PubMed Web of Science ®Google Scholar
• Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018 Dec;19(12):1654–1667. Epub 2018 Nov 6. Erratum in: Lancet Oncol. 2019 Jan;20(1):e10. PMID: 30413378
   PubMed Web of Science ®Google Scholar
• Zhou R, Song L, Zhang W, et al. Combination of osimertinib and anlotinib may overcome the resistance mediated by in cis EGFR T790M-C797S in NSCLC: a case report OncoTargets and Therapy 2020. DOI: 10.2147/OTT.S298655
   Google Scholar
• Martinez-Marti A, Felip E, Matito J, et al. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017;28(10):2451–2457.
   PubMed Web of Science ®Google Scholar
• Sequist LV, Han JY, Ahn MJ, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study. Lancet Oncol. 2020Mar;21(3):373–386. Epub 2020 Feb 3. PMID: 32027846
   PubMed Web of Science ®Google Scholar
• Bauml J, Chul Cho B, Park K, et al. Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response. J Clin Oncol. 2021 May 20;39(15_suppl):9006.
   Web of Science ®Google Scholar
• von Buttlar X, Reuss JE, Liu SV, et al. EML4-ALK rearrangement as a mechanism of resistance to osimertinib in metastatic lung adenocarcinoma: A case report. JTO Clin Res Rep. 2021;2(6):100179.
   PubMedGoogle Scholar
• Rotow J, Patel J, Hanley M, et al. Combination osimertinib plus selpercatinib for EGFR mutant non-small cell lung cancer (NSCLC) with acquired RET fusions. 2021 March 01;16(3):S230.
   Google Scholar
• Kim L, Kwang Chae Y, Mi Jung C, et al. Addition of selpercatinib to overcome osimertinib resistance in non-small cell lung cancer (NSCLC) with acquired RET fusion detected in ctDNA at very low allele frequency. J Clin Oncol. 2021 May 20;39(15_suppl):3046.
   Web of Science ®Google Scholar
• Lazzari C, Gregorc V, Karachaliou N, et al. Mechanisms of resistance to osimertinib. J Thorac Dis. 2020;12(5):2851–2858.
   PubMed Web of Science ®Google Scholar
• Leonetti A, Sharma S, Minari R, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019;121(9):725–737.
   PubMed Web of Science ®Google Scholar
• Okada K, Araki M, Oh-hara T, et al. Predication of lorlatinib resistance mechanisms and therapeutic strategies to overcome the resistance in ALK rearranged non-small cell lung cancer [abstract. In: Proceedings of the AACR-NCI-EORTC international conference on molecular targets and cancer therapeutics. 2019 Oct 26-30. Vol. 18. Boston; MA; Philadelphia (PA):AACR; Mol Cancer Ther. A125. 12 Suppl
   Google Scholar
• Recondo G, Mezquita L, Facchinetti F, et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. Clin Cancer Res. 2020;26(1):242–255.
   PubMed Web of Science ®Google Scholar
• Smolle E, Taucher V, Lindenmann J, et al. Current knowledge about mechanisms of drug resistance against alk inhibitors in non-small cell lung cancer. Cancers (Basel). 2021;13(4):699.
   PubMed Web of Science ®Google Scholar
• Facchinetti F, Lacroix L, Mezquita L, et al. Molecular mechanisms of resistance to BRAF and MEK inhibitors in BRAFV600E non-small cell lung cancer. Eur J Cancer. 2020 Jun;132:211–223. Epub 2020 May 6. PMID: 32388065.
   PubMed Web of Science ®Google Scholar
• D’Angelo A, Sobhani N, Chapman R, et al. Focus on ROS1-positive non-small cell lung cancer (NSCLC): Crizotinib, resistance mechanisms and the newer generation of targeted therapies. Cancers (Basel). 2020;12(11):3293.
   PubMed Web of Science ®Google Scholar
• Lin JJ, Choudhury NJ, Yoda S, et al. Spectrum of mechanisms of resistance to crizotinib and lorlatinib in ROS1 fusion-positive lung cancer. Clin Cancer Res. 2021 May 15;27(10):2899–2909. Epub 2021 Mar 8. PMID: 33685866; PMCID: PMC8127383.
   PubMed Web of Science ®Google Scholar
• Gainor JF, Tseng D, Yoda S, et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ros1-positive non–small-cell lung cancer. JCO Precis Oncol. 2017;1:O.17.00063.
   Web of Science ®Google Scholar
• Majeed U, Manochakian R, Zhao Y, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14(1):108.
   PubMed Web of Science ®Google Scholar
• Yu H, Goldberg S, Le X, et al. P2.01-22 ORCHARD: a phase II platform study in patients with advanced NSCLC who have progressed on first-line osimertinib therapy poster sessions|. 2019 October 01;14(10):S647.*One of the most promising trials involving the use of drug combinations to treat TKI-resistance
   Google Scholar
• Phase 2 platform study in patients with advanced non-small lung cancer who progressed on first-line osimertinib therapy (ORCHARD) (ORCHARD); clinicaltrials.org [internet].ClinicalTrials.gov Identifier: NCT03944772. Accessed Jul 2021 Available at: https://www.clinicaltrials.gov/ct2/show/NCT03944772.
   Google Scholar
• Osimertinib plus savolitinib in EGFRM+/MET+ NSCLC following prior osimertinib (savannah); clinicaltrials.org [internet]. clinicaltrials.gov identifier: NCT03778229 Available at: https://www.clinicaltrials.gov/ct2/show/NCT03778229. Cited Jul 2021
   Google Scholar
• A study of tepotinib plus osimertinib in osimertinib relapsed mesenchymal-epithelial transition factor (MET) amplified non-small cell lung cancer (NSCLC) (INSIGHT 2) (INSIGHT 2); clinicaltrials.org [internet]. ClinicalTrials.gov Identifier: NCT03940703 Available at: Accessed July 2021. https://clinicaltrials.gov/ct2/show/NCT03940703.
   Google Scholar
• T-DM1 and osimertinib combination treatment to target her2 bypass track resistance in egfr mutation positive NSCLC (TRAEMOS); clinicaltrials.org [internet]. clinicaltrials.gov Identifier: NCT03784599. Available at: https://clinicaltrials.gov/ct2/show/NCT03784599. Cited Jul 2021 *One of the most promising trials involving the use of drug combinations to treat TKI-resistance
   Google Scholar
• Addeo A, Passaro A, Malapelle U, et al. Immunotherapy in non-small cell lung cancer harbouring driver mutations. Cancer Treat Rev. 2021 May;96:102179. Epub 2021 Mar 19. PMID: 33798954.
   PubMed Web of Science ®Google Scholar
• Mhanna L, Guibert N, Milia J, et al. When to consider immune checkpoint inhibitors in oncogene-driven non-small cell lung cancer? Curr Treat Options Oncol. 2019;20(7):60.
   PubMed Web of Science ®Google Scholar
• Tsakonas G, Ekman S. Oncogene-addicted non-small cell lung cancer and immunotherapy. J Thorac Dis. 2018;10(Suppl 13):S1547–S1555.
   PubMed Web of Science ®Google Scholar
• Calles A, Riess JW, Brahmer JR. Checkpoint blockade in lung cancer with driver mutation: Choose the road wisely. Am Soc Clin Oncol Educ Book. 2020May; 40: 372–384 PMID: 32421452
   PubMedGoogle Scholar
• Reck M, Mok TSK, Nishio M, et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Epub 2019 Mar 25. PMID: 30922878, Lancet Respir Med. 2019 May;7(5):387–401.
   PubMed Web of Science ®Google Scholar
• Socinski MA, Mok TS, Nishio M, et al. Abstract CT216: Impower150 final analysis: Efficacy of atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups cancer res. 2020 Aug 15;80(16 Supplement):CT216.*First large-scale phase III trial involving chemo-immunotherapy combinations to report favorable survival outcomes for oncogene-addicted advanced NSCLC patients
   Google Scholar