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. 2024 Mar 26;5(8):100669.
doi: 10.1016/j.jtocrr.2024.100669. eCollection 2024 Aug.

Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC

William Tompkins  1 , Connor B Grady  2 , Wei-Ting Hwang  2 , Krishna Chandrasekhara  1 , Caroline McCoach  3 , Fangdi Sun  3 , Geoffrey Liu  4 , Devalben Patel  4 , Jorge Nieva  5 , Amanda Herrmann  5 , Kristen Marrone  6 , Vincent K Lam  6 , Vamsi Velcheti  7 , Stephen V Liu  8 , Gabriela Liliana Bravo Montenegro  8 , Tejas Patil  9 , Jared Weiss  10 , Kelsey Leigh Miller  10 , William Schwartzman  11 , Jonathan E Dowell  11 , Khvaramze Shaverdashvili  12 , Liza Villaruz  12 , Amanda Cass  13 , Wade Iams  13 , Dara Aisner  9 , Charu Aggarwal  14 , D Ross Camidge  9 , Melina E Marmarelis  14 , Lova Sun  14
Affiliations

Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC

William Tompkins et al. JTO Clin Res Rep. .

Abstract

Introduction: Characteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors.

Methods: Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015. Demographics and comutations were compared between greater than or equal to 5-year survivors and less than 5-year survivors. Multivariable Cox proportional hazard and logistic regression models were used to evaluate factors associated with survival and the odds of death within 5 years, respectively.

Results: Overall, 133 patients were greater than or equal to 5-year survivors; 127 were less than 5-year survivors. Burden of pathogenic comutations including TP53 and PIK3CA was similar between greater than or equal to 5-year survivors and less than 5-year survivors. Receipt of first-line chemotherapy rather than EGFR tyrosine kinase inhibitor was similar between the groups (22% of <5-y versus 31% of ≥5-y). Baseline brain metastasis and history of smoking were associated with higher odds of death within 5 years (odds ratio = 2.16, p = 0.029 and odds ratio = 1.90, p = 0.046, respectively). Among patients without baseline brain metastases, cumulative incidence of brain metastases at 5 years was 42.3%. Both baseline and post-baseline brain metastasis were associated with worse overall survival compared with no brain metastasis (hazard ratio = 3.26, p < 0.001 and hazard ratio = 4.99, p < 0.001, respectively).

Conclusions: Within patients treated for EGFRm metastatic NSCLC before 2015, absence of brain metastasis and nonsmoking status were predictive of 5-year survival. Our findings help to define a subset of patients with EGFRm NSCLC with excellent survival outcomes who may not require intensification of initial therapy.

Keywords: Brain metastasis; EGFR; EGFR TKI; NSCLC; Next-generation sequencing.

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Conflict of interest statement

Dr. McCoach reports working as an employee at Genentech. Dr. G. Liu reports receiving institutional grants from NCI, CIHR, CCSRI, AstraZeneca, 10.13039/100016040Takeda, Boehringer Ingelheim, AMGEN, EMD Serono, 10.13039/100004319Pfizer, and 10.13039/100004326Bayer; receiving personal honoraria from AstraZeneca, Pfizer, EMD Serono, and Takeda; and participating on the Data Safety Monitoring Board/Advisory Board for AstraZeneca, Pfizer, EMD Serono, Merck, AbbVie, Jazz, Takeda, Anheart, Roche, Bristol-Myers Squibb, Novartis, and Lilly. Dr. Nieva reports receiving institutional grants from 10.13039/100004328Genentech and Merck; receiving consulting fees from ANP Technologies, Aadi Biosciences, AstraZeneca, BioAtla, G1 Therapeutics, Genentech, Mindmed, Naveris, and Sanofi; receiving travel support from 10.13039/100004325AstraZeneca; having a patent planned with Cansera; participating on the Data Safety Monitoring Board/Advisory Board for Kalivir; and having stock in Amgen, Novartis, Johnson & Johnson, and Cansera. Dr. Marrone reports receiving grants from 10.13039/100016957Mirati Therapeutics and Bristol-Myers Squibb; receiving consulting fees from Daiichi Sankyo, Regeneron, Janssen, Mirati, Amgen, and AstraZeneca; receiving honoraria from Merck, Regeneron, Bristol-Myers Squibb, and AstraZeneca; and participating on the Data Safety Monitoring Board/Advisory Board for Puma. Dr. Lam reports receiving grants from 10.13039/100002491Bristol-Myers Squibb, Merck, SeaGen, and AstraZeneca; receiving consulting fees from SeaGen, Bristol-Myers Squibb, AstraZeneca, Guardant Health, Takeda, and Anheart Therapeutics; and participating on the Data Safety Monitoring Board/Advisory Board for Iovance Therapeutics. Dr. Velcheti reports receiving consulting fees from Bristol-Myers Squibb, Merck, OnCOC4, AstraZeneca, Roche, Novocure, Takeda, Taiho, and Regeneron. Dr. S. Liu reports receiving institutional grants from 10.13039/100006483AbbVie, 10.13039/100018529Alkermes, AstraZeneca, Elevation Oncology, Ellipses, Genentech, Gilead, Merck, Merus, Nuvalent, OSE Immunotherapeutics, Puma, RAPT, and Turning Point Therapeutics; receiving consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Catalyst, Daiichi Sankyo, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Pfizer, RAPT, Regeneron, Revolution Medicines, Sanofi, and Takeda; and participating on a Data Safety Monitoring Board/Advisory Board for Candel Therapeutics. Dr. Patil reports receiving research funding from 10.13039/100004755EMD Serono, 10.13039/100005565Janssen, and 10.13039/100005564Gilead; receiving consulting fees from AstraZeneca, Biocept, Boehringer Ingelheim, Bristol-Myers Squibb, Bicara, Caris, Daiichi, Guardant Health, Guidepoint, EMD Serono, Janssen, Jazz Pharmaceuticals, Mirati Therapeutics, Natera, Pfizer, Sanofi, Regeneron, Roche/Genentech, and Takeda; and participating on the Data Safety Monitoring Board/Advisory Board for Elevation Oncology. Dr. Weiss reports receiving institutional grants from AstraZeneca, 10.13039/100019799G1, Loxo/10.13039/100019518Lilly, Mirati, SDP, BI, and PDS; receiving consulting fees from AZD, EMD Serono, Genentech, G1, Jounce, AbbVie, Nanobiotix, Merck, Sanofi, Gilead, PDS, and AMGEN; participating on a Data Safety Monitoring Board or Advisory Board for Jounce and Beigene; having a leadership or fiduciary role for Cancergrace; and having stock/stock options for Nektar, Vesselon, Achilles, Nuvalent, Lyell, En Fuego, and Vertex. Dr. Dowell reports receiving consulting fees from Takeda, Catalyst, Beigene, and Janssen. Dr. Villaruz reports receiving consulting fees from Sanofi, Gilead, Johnson & Johnson, EMD Serono, Daiichi Sankyo, AstraZeneca, and Janssen. Dr. Cass reports receiving honoraria from OncLive, Medscape, and PharmacyTimes; and participating on the Data Safety Monitoring Board/Advisory Board for G1 Therapeutics, Takeda, and Regeneron. Dr. Iams reports receiving consulting fees from OncLive, Clinical Care Options, Chardan, Cello Health, and Curio Science; and participating on the Data Safety Monitoring Board/Advisory Board for Genentech, Mirati, Outcomes Insights, Jazz Pharmaceuticals, G1 Therapeutics, Takeda, AstraZeneca, Sanofi, Janssen, Amgen, Bristol Myers Squibb, and NovoCure. Dr. Aisner reports receiving consulting fees from Merus, Genentech, Bayer, AbbVie, and AstraZeneca; receiving support for attending meetings from AstraZeneca; and serving as Chair of Board for Genomics Organization for Academic Laboratories. Dr. Aggarwal reportsreceiving consulting fees from Genentech, Lilly, Merck, AstraZeneca, Daiichi Sankyo, Sanofi/Regeneron, Pfizer, Janssen, Boehringer-Ingelheim, Takeda, Arcus Biosciences, Mirati Therapeutics, Gilead Sciences, Novocure, AbbVie, and Jazz Pharmaceuticals; receiving speaking fees from AstraZeneca and Roche/Genentech; and receiving research funding from 10.13039/100004334Merck Sharp & Dohme, AstraZeneca/10.13039/501100004628MedImmune, 10.13039/501100022274Daiichi Sankyo, Loxo@Lilly, and Candel Therapeutics. Dr. Camidge reports receiving honoraria for consulting from AbbVie, Anheart, Beigene, Eli Lilly, Immunocore, Janssen, Prelude, Seattle Genetics, Valence, Appolomics, AstraZeneca/Daiichi, Dizal, EMD Serono, Elevation, Hengrui, Hummingbird, Medtronic, Mersana, Mirati, Nalo Therapeutics, Onkure, Regeneron, Roche, Sanofi, Takeda, Theseus, and Xcovery. Dr. Marmarelis reports receiving research funding from Eli Lilly, AstraZeneca, and Merck; receiving consulting fees from AstraZeneca, Novocure, Boehringer Ingelheim, Janssen, Takeda, Blueprint Pharmaceuticals, Bayer, Bristol Myers Squibb, Ikena, and Regeneron; receiving honoraria from Thermo Fisher; and having stock in Merck and Johnson & Johnson. Dr. Sun reports receiving honoraria from Bayer and participating on the Data Safety Monitoring Board/Advisory Board for Seagen, Sanofi Genzyme, and Regeneron. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study sample and analytic cohorts. ATOMIC, Academic Thoracic Medical Investigator’s Consortium.
Figure 2
Figure 2
Proportion of patients with non-EGFR alterations by survival group. Includes patients with baseline next-generation sequencing, defined as next-generation sequencing samples collected within 1 year before and 60 days after start of first-line treatment (≥5-y survival group, n = 52; <5-y survival group, n = 48). Comutations with greater than 5% prevalence illustrated.
Figure 3
Figure 3
Factors associated with overall survival and odds of death by 5 years after start of frontline therapy. CI, confidence interval; HR, hazard ratio; OR, odds ratio.
Figure 4
Figure 4
Brain metastases over time. (A) Cumulative incidence of brain metastasis over time in patients with baseline imaging and no baseline brain metastasis (n = 97). (B) Extended Kaplan-Meier curves of overall survival by time-dependent brain metastasis status. Patients with no baseline brain metastasis who subsequently developed a brain metastasis during follow-up move across risk sets (i.e., from no baseline brain metastasis to post-baseline brain metastasis) at the time of brain metastasis detection.
Supplementary Figure 1
Supplementary Figure 1
Supplementary Fig. 2
Supplementary Fig. 2
See this image and copyright information in PMC

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References

    1. Zhou C., Wu Y.L., Chen G., et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12:735–742. - PubMed
    1. Rosell R., Carcereny E., Gervais R., et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–246. - PubMed
    1. Mok T.S., Wu Y.L., Thongprasert S., et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–957. - PubMed
    1. Maemondo M., Inoue A., Kobayashi K., et al. Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–2388. - PubMed
    1. Mitsudomi T., Morita S., Yatabe Y., et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–128. - PubMed

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