Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M (2019) Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol 20:625–635. https://doi.org/10.1016/S1470-2045(19)30035-X

Article  PubMed  Google Scholar 

Saito R, Sugawara S, Ko R, Azuma K, Morita R, Maemondo M, Oizumi S, Takahashi K, Kagamu H, Tsubata Y, Seike M, Kikuchi T, Okamoto I, Satoshi M, Asahina H, Tanaka K, Sugio K, Kobayashi K (2023) Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: the OPAL Study. Eur J Cancer 185:83–93. https://doi.org/10.1016/j.ejca.2023.02.023

Article  PubMed  Google Scholar 

Peters S, Bexelius C, Munk V, Leighl N (2016) The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer. Cancer Treat Rev 45:139–162. https://doi.org/10.1016/j.ctrv.2016.03.009

Article  PubMed  Google Scholar 

Popat S, Ahn MJ, Ekman S, Leighl NB, Ramalingam SS, Reungwetwattana T, Siva S, Tsuboi M, Wu YL, Yang JC (2023) Osimertinib for EGFR-mutant non-small-cell lung cancer central nervous system metastases: current evidence and future perspectives on therapeutic strategies. Target Oncol 18:9–24. https://doi.org/10.1007/s11523-022-00941-7

Article  PubMed  Google Scholar 

Schoenmaekers J, Paats MS, Dingemans AC, Hendriks LEL (2020) Central nervous system metastases and oligoprogression during treatment with tyrosine kinase inhibitors in oncogene-addicted non-small cell lung cancer: How to treat and when? Transl Lung Cancer Res 9:2599–2617. https://doi.org/10.21037/tlcr-20-459

Article  PubMed  PubMed Central  Google Scholar 

Soria JC, Ohe Y, Vansteenkiste J, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS (2018) for the FLAURA Investigators: osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378:113–125. https://doi.org/10.1056/NEJMoa1713137

Article  PubMed  Google Scholar 

Vogelbaum MA, Brown PD, Messersmith H, Brastianos PK, Burri S, Cahill D, Dunn IF, Gaspar LE, Gatson NTN, Gondi V, Jordan JT, Lassman AB, Maues J, Mohile N, Redjal N, Stevens G, Sulman E, van den Bent M, Wallace HJ, Weinberg JS, Zadeh G, Schiff D (2022) Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J Clin Oncol 40:492–516. https://doi.org/10.1200/JCO.21.02314

Article  PubMed  Google Scholar 

Passaro A, Leighl N, Blackhall F, Popat S, Kerr K, Ahn MJ, Arcila ME, Arrieta O, Planchard D, de Marinis F, Dingemans AM, Dziadziuszko R, Faivre-Finn C, Feldman J, Felip E, Curigliano G, Herbst R, Jänne PA, John T, Mitsudomi T, Mok T, Normanno N, Paz-Ares L, Ramalingam S, Sequist L, Vansteenkiste J, Wistuba II, Wolf J, Wu YL, Yang SR, Yang JCH, Yatabe Y, Pentheroudakis G, Peters S (2022) ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer. Ann Oncol 33:466–487. https://doi.org/10.1016/j.annonc.2022.02.003

Article  PubMed  Google Scholar 

Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M (2019) RELAY Study Investigators: Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20:1655–1669. https://doi.org/10.1016/S1470-2045(19)30634-5

Article  PubMed  Google Scholar 

Chen F, Chen N, Yu Y, Cui J (2020) Efficacy and safety of epidermal growth factor receptor (EGFR) inhibitors plus antiangiogenic agents as first-line treatments for patients with advanced EGFR-mutated non-small cell lung cancer: a meta-analysis. Front Oncol 10:904. https://doi.org/10.3389/fonc.2020.00904

Article  PubMed  PubMed Central  Google Scholar 

Jiang T, Zhang Y, Li X, Zhao C, Chen X, Su C, Ren S, Yang N, Zhou C (2019) EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in patients with EGFR-mutant NSCLC and multiple brain metastases. Eur J Cancer 121:98–108. https://doi.org/10.1016/j.ejca.2019.08.021

Article  PubMed  Google Scholar 

Kaneda H, Sawa K, Daga H, Okada A, Nakatani Y, Atagi S, Okishio K, Tani Y, Matsumoto Y, Ogawa K, Nakahama K, Izumi M, Mitsuoka S, Kawaguchi T (2021) Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non-small cell lung cancer patients with asymptomatic brain metastases. Invest New Drugs 39:1598–1603. https://doi.org/10.1007/s10637-021-01147-w

Article  PubMed  Google Scholar 

Nishio K, Sakai K, Nishio M, Seto T, Visseren-Grul C, Carlsen M, Matsui T, Enatsu S, Nakagawa K (2023) Impact of ramucirumab plus erlotinib on circulating cell-free DNA from patients with untreated metastatic non-small cell lung cancer with EGFR-activating mutations (RELAY phase 3 randomized study). Transl Lung Cancer Res 12:1702–1716. https://doi.org/10.21037/tlcr-22-736

Article  PubMed  PubMed Central  Google Scholar 

Ishii H, Azuma K, Sakai K, Naito Y, Matsuo N, Tokito T, Yamada K, Hoshino T, Nishio K (2020) Determination of somatic mutations and tumor mutation burden in plasma by CAPP-Seq during afatinib treatment in NSCLC patients resistance to osimertinib. Sci Rep 10:691. https://doi.org/10.1038/s41598-020-57624-4

Article  PubMed  PubMed Central  Google Scholar 

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG (2016) Exome aggregation consortium: analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–291. https://doi.org/10.1038/nature19057

Article  PubMed  PubMed Central  Google Scholar 

Ishii H, Azuma K, Sakai K, Kawahara A, Yamada K, Tokito T, Okamoto I, Nishio K, Hoshino T (2015) Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC: correlation with paired tumor samples. Oncotarget 6:30850–30858. https://doi.org/10.18632/oncotarget.5068

Article  PubMed  PubMed Central  Google Scholar 

Le X, Patel J, Shum E, Sanborn RE, Baik CS, Shu CA, Kim C, Fidler MD, Hall R, Hanna N, Mohindra N, Sabari JK, Heeke S, Hernandez M, Gray JE, Heymach JV, Saltos A (2023) LBA71 A multi centre open label randomized phase ii study of osimertinib with and without ramucirumab in TKI naïve EGFR mutant metastatic NSCLC (RAMOSE trial). Ann Oncol 34:S1313–S1314. https://doi.org/10.1016/j.annonc.2023.10.072

Article  Google Scholar 

Misumi T, Tamiya M, Yoh K, Furuya N, Ono A, Takiguchi Y, Koyama K, Ikeda S, Watanabe K, Tokito T, Seki N, Imai H, Shukuya T, Shibata Y, Hosokawa S, Kozuki T, Okamoto H (2023) LBA70 OSIRAM 1: A multicenter, open label, randomized phase II study of osimertinib plus ramucirumab versus osimertinib alone as initial chemotherapy for EGFR mutation-positive non-squamous non small cell lung cancer (TORG1833). Ann Oncol 34:1313. https://doi.org/10.1016/j.annonc.2023.10.071

Article  Google Scholar 

Blakely CM, Watkins TBK, Wu W, Gini B, Chabon JJ, McCoach CE, McGranahan N, Wilson GA, Birkbak NJ, Olivas VR, Rotow J, Maynard A, Wang V, Gubens MA, Banks KC, Lanman RB, Caulin AF, St John J, Cordero AR, Giannikopoulos P, Simmons AD, Mack PC, Gandara DR, Husain H, Doebele RC, Riess JW, Diehn M, Swanton C, Bivona TG (2017) Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet 49:1693–1704. https://doi.org/10.1038/ng.3990

Article  PubMed  PubMed Central  Google Scholar 

Skoulidis F, Heymach JV (2019) Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer 19:495–509. https://doi.org/10.1038/s41568-019-0179-8

Article  PubMed  PubMed Central  Google Scholar 

Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, Chang MT, Ni A, Kundra R, Jonsson P, Jayakumaran G, Gao SP, Johnsen HC, Hanrahan AJ, Zehir A, Rekhtman N, Ginsberg MS, Li BT, Yu HA, Paik PK, Drilon A, Hellmann MD, Reales DN, Benayed R, Rusch VW, Kris MG, Chaft JE, Baselga J, Taylor BS, Schultz N, Rudin CM, Hyman DM, Berger MF, Solit DB, Ladanyi M, Riely GJ (2017) Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov 7:596–609. https://doi.org/10.1158/2159-8290.CD-16-1337

Article  PubMed  PubMed Central  Google Scholar 

Canale M, Petracci E, Delmonte A, Chiadini E, Dazzi C, Papi M, Capelli L, Casanova C, De Luigi N, Mariotti M, Gamboni A, Chiari R, Bennati C, Calistri D, Ludovini V, Crinò L, Amadori D, Ulivi P (2017) Impact of TP53 mutations on outcome in EGFR-mutated patients treated with first-line tyrosine kinase inhibitors. Clin Cancer Res 23:2195–2202. https://doi.org/10.1158/1078-0432.CCR-16-0966

Article  PubMed  Google Scholar 

Aggarwal C, Davis CW, Mick R, Thompson JC, Ahmed S, Jeffries S, Bagley S, Gabriel P, Evans TL, Bauml JM, Ciunci C, Alley E, Morrissette JJD, Cohen RB, Carpenter EL, Langer CJ (2018) Influence of TP53 mutation on survival in patients with advanced EGFR-mutant non-small-cell lung cancer. JCO Precis Oncol 2. https://doi.org/10.1200/PO.18.00107

Qin K, Hou H, Liang Y, Zhang X (2020) Prognostic value of TP53 concurrent mutations for EGFR-TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis. BMC Cancer 20:328. https://doi.org/10.1186/s12885-020-06805-5

Article  PubMed  PubMed Central  Google Scholar 

Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K (2021) Genetic determinants of EGFR-driven lung cancer growth and therapeutic response in vivo. Cancer Discov 11:1736–1753. https://doi.org/10.1158/2159-8290.CD-20-1385

Article