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3. An atlas of epithelial cell states and plasticity in lung adenocarcinoma

Author

Han, Guangchun, Sinjab, Ansam, Rahal, Zahraa, Lynch, Anne M., Treekitkarnmongkol, Warapen, Liu, Yuejiang, Serrano, Alejandra G., Feng, Jiping, Liang, Ke, Khan, Khaja, Lu, Wei, Hernandez, Sharia D., Liu, Yunhe, Cao, Xuanye, Dai, Enyu, Pei, Guangsheng, Hu, Jian, Abaya, Camille, Gomez-Bolanos, Lorena I., Peng, Fuduan, Chen, Minyue, Parra, Edwin R., Cascone, Tina, Sepesi, Boris, Moghaddam, Seyed Javad, Scheet, Paul, Negrao, Marcelo V., Heymach, John V., Li, Mingyao, Dubinett, Steven M., Stevenson, Christopher S., Spira, Avrum E., Fujimoto, Junya, Solis, Luisa M., Wistuba, Ignacio I., Chen, Jichao, Wang, Linghua, and Kadara, Humam

Published
2024
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5. Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

Author

Hong, Lingzhi, Aminu, Muhammad, Li, Shenduo, Lu, Xuetao, Petranovic, Milena, Saad, Maliazurina B., Chen, Pingjun, Qin, Kang, Varghese, Susan, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y., Negrao, Marcelo V., Skoulidis, Ferdinandos, Gay, Carl M., Cascone, Tina, Gandhi, Saumil J., Lin, Steven H., Lee, Percy P., Carter, Brett W., Wu, Carol C., Antonoff, Mara B., Sepesi, Boris, Lewis, Jeff, Gibbons, Don L., Vaporciyan, Ara A., Le, Xiuning, Jack Lee, J., Roy-Chowdhuri, Sinchita, Routbort, Mark J., Gainor, Justin F., Heymach, John V., Lou, Yanyan, Wu, Jia, Zhang, Jianjun, and Vokes, Natalie I.

Published
2023
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6. Author Correction: An atlas of epithelial cell states and plasticity in lung adenocarcinoma

Author

Han, Guangchun, Sinjab, Ansam, Rahal, Zahraa, Lynch, Anne M., Treekitkarnmongkol, Warapen, Liu, Yuejiang, Serrano, Alejandra G., Feng, Jiping, Liang, Ke, Khan, Khaja, Lu, Wei, Hernandez, Sharia D., Liu, Yunhe, Cao, Xuanye, Dai, Enyu, Pei, Guangsheng, Hu, Jian, Abaya, Camille, Gomez-Bolanos, Lorena I., Peng, Fuduan, Chen, Minyue, Parra, Edwin R., Cascone, Tina, Sepesi, Boris, Moghaddam, Seyed Javad, Scheet, Paul, Negrao, Marcelo V., Heymach, John V., Li, Mingyao, Dubinett, Steven M., Stevenson, Christopher S., Spira, Avrum E., Fujimoto, Junya, Solis, Luisa M., Wistuba, Ignacio I., Chen, Jichao, Wang, Linghua, and Kadara, Humam

Published
2024
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7. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Author

Cascone, Tina, Leung, Cheuk H., Weissferdt, Annikka, Pataer, Apar, Carter, Brett W., Godoy, Myrna C. B., Feldman, Hope, William, Jr, William N., Xi, Yuanxin, Basu, Sreyashi, Sun, Jing Jing, Yadav, Shalini S., Rojas Alvarez, Frank R., Lee, Younghee, Mishra, Aditya K., Chen, Lili, Pradhan, Monika, Guo, Haiping, Sinjab, Ansam, Zhou, Nicolas, Negrao, Marcelo V., Le, Xiuning, Gay, Carl M., Tsao, Anne S., Byers, Lauren Averett, Altan, Mehmet, Glisson, Bonnie S., Fossella, Frank V., Elamin, Yasir Y., Blumenschein, Jr, George, Zhang, Jianjun, Skoulidis, Ferdinandos, Wu, Jia, Mehran, Reza J., Rice, David C., Walsh, Garrett L., Hofstetter, Wayne L., Rajaram, Ravi, Antonoff, Mara B., Fujimoto, Junya, Solis, Luisa M., Parra, Edwin R., Haymaker, Cara, Wistuba, Ignacio I., Swisher, Stephen G., Vaporciyan, Ara A., Lin, Heather Y., Wang, Jing, Gibbons, Don L., Jack Lee, J., Ajami, Nadim J., Wargo, Jennifer A., Allison, James P., Sharma, Padmanee, Kadara, Humam, Heymach, John V., and Sepesi, Boris

Published
2023
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9. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study

Author

Saad, Maliazurina B, Hong, Lingzhi, Aminu, Muhammad, Vokes, Natalie I, Chen, Pingjun, Salehjahromi, Morteza, Qin, Kang, Sujit, Sheeba J, Lu, Xuetao, Young, Elliana, Al-Tashi, Qasem, Qureshi, Rizwan, Wu, Carol C, Carter, Brett W, Lin, Steven H, Lee, Percy P, Gandhi, Saumil, Chang, Joe Y, Li, Ruijiang, Gensheimer, Michael F, Wakelee, Heather A, Neal, Joel W, Lee, Hyun-Sung, Cheng, Chao, Velcheti, Vamsidhar, Lou, Yanyan, Petranovic, Milena, Rinsurongkawong, Waree, Le, Xiuning, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y, Negrao, Marcelo V, Skoulidis, Ferdinandos, Gay, Carl M, Cascone, Tina, Antonoff, Mara B, Sepesi, Boris, Lewis, Jeff, Wistuba, Ignacio I, Hazle, John D, Chung, Caroline, Jaffray, David, Gibbons, Don L, Vaporciyan, Ara, Lee, J Jack, Heymach, John V, Zhang, Jianjun, and Wu, Jia

Published
2023
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11. Molecular Landscape of BRAF-Mutant NSCLC Reveals an Association Between Clonality and Driver Mutations and Identifies Targetable Non-V600 Driver Mutations

Author

Negrao, Marcelo V, Raymond, Victoria M, Lanman, Richard B, Robichaux, Jacqulyne P, He, Junqin, Nilsson, Monique B, Ng, Patrick KS, Amador, Bianca E, Roarty, Emily B, Nagy, Rebecca J, Banks, Kimberly C, Zhu, Viola W, Ng, Chun, Chae, Young Kwang, Clarke, Jeffrey M, Crawford, Jeffrey A, Meric-Bernstam, Funda, Ignatius Ou, Sai-Hong, Gandara, David R, Heymach, John V, Bivona, Trever G, and McCoach, Caroline E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Lung, Human Genome, Lung Cancer, Genetics, Cancer, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Aetiology, 5.1 Pharmaceuticals, Good Health and Well Being, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Non-small cell lung cancer, BRAF, Targeted therapy, Cell-free DNA, Non–small cell lung cancer, Cardiorespiratory Medicine and Haematology, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

IntroductionApproximately 4% of NSCLC harbor BRAF mutations, and approximately 50% of these are non-V600 mutations. Treatment of tumors harboring non-V600 mutations is challenging because of functional heterogeneity and lack of knowledge regarding their clinical significance and response to targeted agents.MethodsWe conducted an integrative analysis of BRAF non-V600 mutations using genomic profiles of BRAF-mutant NSCLC from the Guardant360 database. BRAF mutations were categorized by clonality and class (1 and 2: RAS-independent; 3: RAS-dependent). Cell viability assays were performed in Ba/F3 models. Drug screens were performed in NSCLC cell lines.ResultsA total of 305 unique BRAF mutations were identified. Missense mutations were most common (276, 90%), and 45% were variants of unknown significance. F468S and N581Y were identified as novel activating mutations. Class 1 to 3 mutations had higher clonality than mutations of unknown class (p < 0.01). Three patients were treated with MEK with or without BRAF inhibitors. Patients harboring G469V and D594G mutations did not respond, whereas a patient with the L597R mutation had a durable response. Trametinib with or without dabrafenib, LXH254, and lifirafenib had more potent inhibition of BRAF non-V600-mutant NSCLC cell lines than other MEK, BRAF, and ERK inhibitors, comparable with the inhibition of BRAF V600E cell line.ConclusionsIn BRAF-mutant NSCLC, clonality is higher in known functional mutations and may allow identification of variants of unknown significance that are more likely to be oncogenic drivers. Our data indicate that certain non-V600 mutations are responsive to MEK and BRAF inhibitors. This integration of genomic profiling and drug sensitivity may guide the treatment for BRAF-mutant NSCLC.

Published
2020

12. Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With Programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Blockade–Resistant Advanced NSCLC

Author

Negrao, Marcelo V., Papadimitrakopoulou, Vassiliki A., Price, Andrew C., Tam, Alda L., Furqan, Muhammad, Laroia, Sandeep T., Massarelli, Erminia, Pacheco, Jose, Heymach, John V., Tsao, Anne S., Walker, Gary V., Vora, Lalit, Mauro, David, Kelley, Heather, Wooldridge, James E., Krieg, Arthur M., and Niu, Jiaxin

Published
2023
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13. Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer

Author

Zhang, Bingnan, Stewart, C. Allison, Wang, Qi, Cardnell, Robert J., Rocha, Pedro, Fujimoto, Junya, Solis Soto, Luisa M., Wang, Runsheng, Novegil, Veronica, Ansell, Peter, He, Lei, Fernandez, Luisa, Jendrisak, Adam, Gilbertson, Cole, Schonhoft, Joseph D., Byun, Jiyun, Jones, Joshua, Anderson, Amanda K. L., Aparicio, Ana, Tran, Hai, Negrao, Marcelo V., Zhang, Jianjun, Wang, Wei-lien, Wistuba, Ignacio I., Wang, Jing, Wenstrup, Rick, Byers, Lauren A., and Gay, Carl M.

Published
2022
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14. Surgical outcomes after neoadjuvant nivolumab or nivolumab with ipilimumab in patients with non–small cell lung cancer

Author

Sepesi, Boris, Zhou, Nicolas, William, William N., Jr., Lin, Heather Y., Leung, Cheuk H., Weissferdt, Annikka, Mitchell, Kyle G., Pataer, Apar, Walsh, Garrett L., Rice, David C., Roth, Jack A., Mehran, Reza J., Hofstetter, Wayne L., Antonoff, Mara B., Rajaram, Ravi, Negrao, Marcelo V., Tsao, Anne S., Gibbons, Don L., Lee, J. Jack, Heymach, John V., Vaporciyan, Ara A., Swisher, Stephen G., and Cascone, Tina

Published
2022
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15. Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity

Author

Elamin, Yasir Y., Robichaux, Jacqulyne P., Carter, Brett W., Altan, Mehmet, Tran, Hai, Gibbons, Don L., Heeke, Simon, Fossella, Frank V., Lam, Vincent K., Le, Xiuning, Negrao, Marcelo V., Nilsson, Monique B., Patel, Anisha, Vijayan, R.S.K., Cross, Jason B., Zhang, Jianjun, Byers, Lauren A., Lu, Charles, Cascone, Tina, Feng, Lei, Luthra, Rajyalakshmi, San Lucas, Francis A., Mantha, Geeta, Routbort, Mark, Blumenschein, George, Jr., Tsao, Anne S., and Heymach, John V.

Published
2022
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16. Real-World Efficacy and Safety of Amivantamab for EGFR-Mutant NSCLC

Author

Wang, Kaiwen, primary, Du, Robyn, additional, Myall, Nathaniel J., additional, Lewis, Whitney E., additional, Uy, Natalie, additional, Hong, Lingzhi, additional, Skoulidis, Ferdinandos, additional, Byers, Lauren A., additional, Tsao, Anne, additional, Cascone, Tina, additional, Pozadzides, Jenny, additional, Tu, Janet, additional, Negrao, Marcelo V., additional, Gibbons, Don L., additional, Park, Keunchil, additional, Rinsurongkawong, Waree, additional, Lee, J. Jack, additional, Gandara, David, additional, Behl, Deepti, additional, Shu, Catherine A., additional, Riess, Jonathan W., additional, Baik, Christina, additional, Wakelee, Heather A., additional, Vaporciyan, Ara A., additional, Heymach, John V., additional, Zhang, Jianjun, additional, and Le, Xiuning, additional

Published
2024
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18. Characterization of the Immune Landscape of EGFR-Mutant NSCLC Identifies CD73/Adenosine Pathway as a Potential Therapeutic Target

Author

Le, Xiuning, Negrao, Marcelo V., Reuben, Alexandre, Federico, Lorenzo, Diao, Lixia, McGrail, Daniel, Nilsson, Monique, Robichaux, Jacqulyne, Munoz, Irene Guijarro, Patel, Sonia, Elamin, Yasir, Fan, You-Hong, Lee, Won-Chul, Parra, Edwin, Solis Soto, Luisa Maren, Chen, Runzhe, Li, Jun, Karpinets, Tatiana, Khairullah, Roohussaba, Kadara, Humam, Behrens, Carmen, Sepesi, Boris, Wang, Ruiping, Zhu, Mingrui, Wang, Linghua, Vaporciyan, Ara, Roth, Jack, Swisher, Stephen, Haymaker, Cara, Zhang, Jianhua, Wang, Jing, Wong, Kwok-Kin, Byers, Lauren A., Bernatchez, Chantale, Zhang, Jianjun, Wistuba, Ignacio I., Gibbons, Don L., Akbay, Esra A., and Heymach, John V.

Published
2021
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19. Mutational Characteristics and Clinical Outcomes for Lung Adenocarcinoma With EGFRGermline Mutations

Author

Pan, Kelsey, Owens, Jennifer, Elamin, Yasir, Lu, Charles, Routbort, Mark, Zhang, Jianjun, Fossella, Frank, Negrao, Marcelo V., Altan, Mehmet, Pozadzides, Jenny, Skoulidis, Ferdinandos, Tsao, Anne, Cascone, Tina, Heymach, John V., Ostrin, Edwin, and Le, Xiuning

Abstract

Germline mutations driving lung cancer have been infrequently reported in the literature, with EGFRT790M being a known germline mutation identified in 1% of NSCLCs. Typically, a somatic EGFRmutation is acquired to develop lung adenocarcinoma. Osimertinib has become a standard-of-care treatment for EGFRT790M-positive lung cancer.

Published
2024
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20. Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC

Author

Gaudreau, Pierre-Olivier, Negrao, Marcelo V., Mitchell, Kyle G., Reuben, Alexandre, Corsini, Erin M., Li, Jun, Karpinets, Tatiana V., Wang, Qi, Diao, Lixia, Wang, Jing, Federico, Lorenzo, Parra-Cuentas, Edwin R., Khairullah, Roohussaba, Behrens, Carmen, Correa, Arlene M., Gomez, Daniel, Little, Latasha, Gumbs, Curtis, Kadara, Humam N., Fujimoto, Junya, McGrail, Daniel J., Vaporciyan, Ara A., Swisher, Stephen G., Walsh, Garrett, Antonoff, Mara B., Weissferdt, Annikka, Tran, Hai, Roarty, Emily, Haymaker, Cara, Bernatchez, Chantale, Zhang, Jianhua, Futreal, P. Andrew, Wistuba, Ignacio I., Cascone, Tina, Heymach, John V., Sepesi, Boris, Zhang, Jianjun, and Gibbons, Don L.

Published
2021
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21. BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape.

Author

Planchard, David, Sanborn, Rachel E., Negrao, Marcelo V., Vaishnavi, Aria, and Smit, Egbert F.

Subjects
THERAPEUTICS, NON-small-cell lung carcinoma, METASTASIS, BRAF genes, MITOGEN-activated protein kinases
Abstract

In this review, we cover the current understanding of BRAF mutations and associated clinical characteristics in patients with metastatic NSCLC, approved and emerging treatment options, BRAF sequencing approaches, and unmet needs. The BRAFV600E mutation confers constitutive activity of the MAPK pathway, leading to enhanced growth, proliferation, and survival of tumor cells. Testing for BRAF mutations enables patients to be treated with therapies that directly target BRAFV600E and the MAPK pathway, but BRAF testing lags behind other oncogene testing in metastatic NSCLC. Additional therapies targeting BRAFV600E mutations provide options for patients with metastatic NSCLC. Emerging therapies and combinations under investigation could potentially overcome issues of resistance and target non-V600E mutations. Therefore, because targeted therapies with enhanced efficacy are on the horizon, being able to identify BRAF mutations in metastatic NSCLC may become even more important. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC

Author

Hong, Lingzhi, Negrao, Marcelo V., Dibaj, Seyedeh S., Chen, Runzhe, Reuben, Alexandre, Bohac, Jadi M., Liu, Xiaoke, Skoulidis, Ferdinandos, Gay, Carl M., Cascone, Tina, Mitchell, Kyle G., Tran, Hai T., Le, Xiuning, Byers, Lauren A., Sepesi, Boris, Altan, Mehmet, Elamin, Yasir Y., Fossella, Frank V., Kurie, Jonathan M., Lu, Charles, Mott, Frank E., Tsao, Anne S., Rinsurongkawong, Waree, Lewis, Jeff, Gibbons, Don L., Glisson, Bonnie S., Blumenschein, George R., Jr., Roarty, Emily B., Futreal, P. Andrew, Wistuba, Ignacio I., Roth, Jack A., Swisher, Stephen G., Papadimitrakopoulou, Vassiliki A., Heymach, John V., Lee, J. Jack, Simon, George R., and Zhang, Jianjun

Published
2020
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23. STING Pathway Expression Identifies NSCLC With an Immune-Responsive Phenotype

Author

Della Corte, Carminia M., Sen, Triparna, Gay, Carl M., Ramkumar, Kavya, Diao, Lixia, Cardnell, Robert J., Rodriguez, Bertha Leticia, Stewart, C. Allison, Papadimitrakopoulou, Vassiliki A., Gibson, Laura, Fradette, Jared J., Wang, Qi, Fan, Youhong, Peng, David H., Negrao, Marcelo V., Wistuba, Ignacio I., Fujimoto, Junya, Solis Soto, Luisa M., Behrens, Carmen, Skoulidis, Ferdinandos, Heymach, John V., Wang, Jing, Gibbons, Don L., and Byers, Lauren A.

Published
2020
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24. The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics

Author

Tang, Ming, Abbas, Hussein A., Negrao, Marcelo V., Ramineni, Maheshwari, Hu, Xin, Hubert, Shawna Marie, Fujimoto, Junya, Reuben, Alexandre, Varghese, Susan, Zhang, Jianhua, Li, Jun, Chow, Chi-Wan, Mao, Xizeng, Song, Xingzhi, Lee, Won-Chul, Wu, Jia, Little, Latasha, Gumbs, Curtis, Behrens, Carmen, Moran, Cesar, Weissferdt, Annikka, Lee, J. Jack, Sepesi, Boris, Swisher, Stephen, Cheng, Chao, Kurie, Jonathan, Gibbons, Don, Heymach, John V., Wistuba, Ignacio I., Futreal, P. Andrew, Kalhor, Neda, and Zhang, Jianjun

Published
2021
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25. Shared Nearest Neighbors Approach and Interactive Browser for Network Analysis of a Comprehensive Non–Small-Cell Lung Cancer Data Set

Author

Schmidt, Stephanie T., Akhave, Neal, Knightly, Ryan E., Reuben, Alexandre, Vokes, Natalie, Zhang, Jianhua, Li, Jun, Fujimoto, Junya, Byers, Lauren A., Sanchez-Espiridion, Beatriz, Diao, Lixia, Wang, Jing, Federico, Lorenzo, Forget, Marie-Andree, McGrail, Daniel J., Weissferdt, Annikka, Lin, Shiaw-Yih, Lee, Younghee, Suzuki, Erika, Kovacs, Jeffrey J., Behrens, Carmen, Wistuba, Ignacio I., Futreal, Andrew, Vaporciyan, Ara, Sepesi, Boris, Heymach, John V., Bernatchez, Chantale, Haymaker, Cara, Cascone, Tina, Zhang, Jianjun, Bristow, Christopher A., Heffernan, Timothy P., Negrao, Marcelo V., and Gibbons, Don L.

Published
2022
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26. PD-L1 Expression, Tumor Mutational Burden, and Cancer Gene Mutations Are Stronger Predictors of Benefit from Immune Checkpoint Blockade than HLA Class I Genotype in Non–Small Cell Lung Cancer

Author

Negrao, Marcelo V., Lam, Vincent K., Reuben, Alexandre, Rubin, Maria Laura, Landry, Lara Lacerda, Roarty, Emily B., Rinsurongkawong, Waree, Lewis, Jeff, Roth, Jack A., Swisher, Stephen G., Gibbons, Don L., Wistuba, Ignacio I., Papadimitrakopoulou, Vassiliki, Glisson, Bonnie S., Blumenschein, George R., Jr., Lee, J. Jack, Heymach, John V., and Zhang, Jianjun

Published
2019
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27. Landscape and Clonal Dominance of Co-occurring Genomic Alterations in Non–Small-Cell Lung Cancer Harboring MET Exon 14 Skipping

Author

Le, Xiuning, Hong, Lingzhi, Hensel, Chuck, Chen, Rongrong, Kemp, Haley, Coleman, Niamh, Ciunci, Christine A., Liu, Stephen V., Negrao, Marcelo V., Yen, Jennifer, Xia, Xuefeng, Scheuenpflug, Juergen, Stroh, Christopher, Juraeva, Dilafruz, Tsao, Anne, Hong, David, Raymond, Victoria, Paik, Paul, Zhang, Jianjun, and Heymach, John V.

Published
2021
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28. Safety and Intracranial Activity of Adagrasib in Patients With KRAS G12C -Mutated Non–Small-Cell Lung Cancer and Untreated CNS Metastases in the KRYSTAL-1 Trial: A Case Series.

Author

Bernstein, Ezra, Luo, Jia, Wang, Kaiwen, Negrao, Marcelo V., Jänne, Pasi A., and Sabari, Joshua K.

Subjects
NON-small-cell lung carcinoma, RAS oncogenes, METASTASIS, ISCHEMIC colitis
Abstract

This document provides a summary of a clinical trial that investigated the use of adagrasib, a KRASG12C inhibitor, in non-small cell lung cancer (NSCLC) patients with untreated central nervous system (CNS) metastases. The study found that adagrasib showed promising results in treating CNS metastases, with a high objective response rate and disease control rate. The document presents five patient cases that highlight different scenarios in which adagrasib was used, demonstrating its potential effectiveness in various clinical situations. However, due to the limited number of patients and follow-up, further research is needed to draw definitive conclusions about the CNS activity of adagrasib. The document also includes information about data sharing and potential conflicts of interest. [Extracted from the article]

Published
2024
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29. ATM Mutations Associate with Distinct Co-Mutational Patterns and Therapeutic Vulnerabilities in NSCLC

Author

Vokes, Natalie I., primary, Galan Cobo, Ana, additional, Fernandez-Chas, Margarita, additional, Molkentine, David, additional, Treviño, Santiago, additional, Druker, Vitaly, additional, Qian, Yu, additional, Patel, Sonia, additional, Schmidt, Stephanie, additional, Hong, Lingzhi, additional, Lewis, Jeff, additional, Rinsurongkawong, Waree, additional, Rinsurongkawong, Vadeerat, additional, Lee, J. Jack, additional, Negrao, Marcelo V., additional, Gibbons, Don L., additional, Vaporciyan, Ara, additional, Le, Xiuning, additional, Wu, Jia, additional, Zhang, Jianjun, additional, Rigney, Una, additional, Iyer, Sonia, additional, Dean, Emma, additional, and Heymach, John V., additional

Published
2023
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30. Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Author

Lee, Won-Chul, Reuben, Alexandre, Hu, Xin, McGranahan, Nicholas, Chen, Runzhe, Jalali, Ali, Negrao, Marcelo V., Hubert, Shawna M., Tang, Chad, Wu, Chia-Chin, Lucas, Anthony San, Roh, Whijae, Suda, Kenichi, Kim, Jihye, Tan, Aik-Choon, Peng, David H., Lu, Wei, Tang, Ximing, Chow, Chi-Wan, Fujimoto, Junya, Behrens, Carmen, Kalhor, Neda, Fukumura, Kazutaka, Coyle, Marcus, Thornton, Rebecca, Gumbs, Curtis, Li, Jun, Wu, Chang-Jiun, Little, Latasha, Roarty, Emily, Song, Xingzhi, Lee, J. Jack, Sulman, Erik P., Rao, Ganesh, Swisher, Stephen, Diao, Lixia, Wang, Jing, Heymach, John V., Huse, Jason T., Scheet, Paul, Wistuba, Ignacio I., Gibbons, Don L., Futreal, P. Andrew, Zhang, Jianhua, Gomez, Daniel, and Zhang, Jianjun

Published
2020
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31. Supplementary Figure S10 from Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC

Author

Negrao, Marcelo V., primary, Araujo, Haniel A., primary, Lamberti, Giuseppe, primary, Cooper, Alissa J., primary, Akhave, Neal S., primary, Zhou, Teng, primary, Delasos, Lukas, primary, Hicks, J. Kevin, primary, Aldea, Mihaela, primary, Minuti, Gabriele, primary, Hines, Jacobi, primary, Aredo, Jacqueline V., primary, Dennis, Michael J., primary, Chakrabarti, Turja, primary, Scott, Susan C., primary, Bironzo, Paolo, primary, Scheffler, Matthias, primary, Christopoulos, Petros, primary, Stenzinger, Albrecht, primary, Riess, Jonathan W., primary, Kim, So Yeon, primary, Goldberg, Sarah B., primary, Li, Mingjia, primary, Wang, Qi, primary, Qing, Yun, primary, Ni, Ying, primary, Do, Minh Truong, primary, Lee, Richard, primary, Ricciuti, Biagio, primary, Alessi, Joao Victor, primary, Wang, Jing, primary, Resuli, Blerina, primary, Landi, Lorenza, primary, Tseng, Shu-Chi, primary, Nishino, Mizuki, primary, Digumarthy, Subba R., primary, Rinsurongkawong, Waree, primary, Rinsurongkawong, Vadeerat, primary, Vaporciyan, Ara A., primary, Blumenschein, George R., primary, Zhang, Jianjun, primary, Owen, Dwight H., primary, Blakely, Collin M., primary, Mountzios, Giannis, primary, Shu, Catherine A., primary, Bestvina, Christine M., primary, Garassino, Marina Chiara, primary, Marrone, Kristen A., primary, Gray, Jhanelle E., primary, Patel, Sandip Pravin, primary, Cummings, Amy L., primary, Wakelee, Heather A., primary, Wolf, Juergen, primary, Scagliotti, Giorgio Vittorio, primary, Cappuzzo, Federico, primary, Barlesi, Fabrice, primary, Patil, Pradnya D., primary, Drusbosky, Leylah, primary, Gibbons, Don L., primary, Meric-Bernstam, Funda, primary, Lee, J. Jack, primary, Heymach, John V., primary, Hong, David S., primary, Heist, Rebecca S., primary, Awad, Mark M., primary, and Skoulidis, Ferdinandos, primary

Published
2023
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32. Data from Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC

Author

Negrao, Marcelo V., primary, Araujo, Haniel A., primary, Lamberti, Giuseppe, primary, Cooper, Alissa J., primary, Akhave, Neal S., primary, Zhou, Teng, primary, Delasos, Lukas, primary, Hicks, J. Kevin, primary, Aldea, Mihaela, primary, Minuti, Gabriele, primary, Hines, Jacobi, primary, Aredo, Jacqueline V., primary, Dennis, Michael J., primary, Chakrabarti, Turja, primary, Scott, Susan C., primary, Bironzo, Paolo, primary, Scheffler, Matthias, primary, Christopoulos, Petros, primary, Stenzinger, Albrecht, primary, Riess, Jonathan W., primary, Kim, So Yeon, primary, Goldberg, Sarah B., primary, Li, Mingjia, primary, Wang, Qi, primary, Qing, Yun, primary, Ni, Ying, primary, Do, Minh Truong, primary, Lee, Richard, primary, Ricciuti, Biagio, primary, Alessi, Joao Victor, primary, Wang, Jing, primary, Resuli, Blerina, primary, Landi, Lorenza, primary, Tseng, Shu-Chi, primary, Nishino, Mizuki, primary, Digumarthy, Subba R., primary, Rinsurongkawong, Waree, primary, Rinsurongkawong, Vadeerat, primary, Vaporciyan, Ara A., primary, Blumenschein, George R., primary, Zhang, Jianjun, primary, Owen, Dwight H., primary, Blakely, Collin M., primary, Mountzios, Giannis, primary, Shu, Catherine A., primary, Bestvina, Christine M., primary, Garassino, Marina Chiara, primary, Marrone, Kristen A., primary, Gray, Jhanelle E., primary, Patel, Sandip Pravin, primary, Cummings, Amy L., primary, Wakelee, Heather A., primary, Wolf, Juergen, primary, Scagliotti, Giorgio Vittorio, primary, Cappuzzo, Federico, primary, Barlesi, Fabrice, primary, Patil, Pradnya D., primary, Drusbosky, Leylah, primary, Gibbons, Don L., primary, Meric-Bernstam, Funda, primary, Lee, J. Jack, primary, Heymach, John V., primary, Hong, David S., primary, Heist, Rebecca S., primary, Awad, Mark M., primary, and Skoulidis, Ferdinandos, primary

Published
2023
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33. Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial

Author

Altan, Mehmet, primary, Wang, Yan, additional, Song, Juhee, additional, Welsh, James, additional, Tang, Chad, additional, Guha-Thakurta, Nandita, additional, Blumenschein, George R, additional, Carter, Brett W, additional, Wefel, Jeffrey S, additional, Ghia, Amol J, additional, Yeboa, Debra N, additional, McAleer, Mary Frances, additional, Chung, Caroline, additional, Woodhouse, Kristina D, additional, McGovern, Susan L, additional, Wang, Chenyang, additional, Kim, Betty Y S, additional, Weinberg, Jeffrey S, additional, Briere, Tina M, additional, Elamin, Yasir Y, additional, Le, Xiuning, additional, Cascone, Tina, additional, Negrao, Marcelo V, additional, Skoulidis, Ferdinandos, additional, Ferrarotto, Renata, additional, Heymach, John V, additional, and Li, Jing, additional

Published
2023
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34. Sympathetic neural overdrive and diminished exercise capacity in reduced ejection fraction heart failure related to anthracycline-based chemotherapy.

Author

Rodrigues, Amanda G., Sales, Allan R. K., Faria, Diego, Fonseca, Silvia M. R., Bond, Marina M. K., Jordão, Camila P., de Souza, Francis R., Bittar, Cristina S., Dos Santos, Marília H. H., Sarmento, Adriana O., Negrao, Marcelo V., Hajjar, Ludhmila A., Negrão, Carlos E., and Filho, Roberto Kalil

Abstract

Cardiotoxicity is the most worrying cardiovascular alteration in patients treated with chemotherapy. To improve the understanding regarding the cardiotoxicity, we studied whether 1) patients with cardiac dysfunction related to anthracycline-based chemotherapy have augmented sympathetic nerve activity and decreased exercise capacity and 2) these responses are similar to those observed in patients with heart failure caused by other etiologies. Sixteen patients with heart failure with reduced ejection fraction related to anthracycline-based chemotherapy with or without chest radiation (HFrEFCA), 10 patients with heart failure with reduced ejection not related to cancer therapy (HFrEF), and 16 age-and body mass index (BMI)-matched healthy control subjects were studied. Left ventricular ejection fraction (LVEF, echocardiography), peak oxygen consumption (peak VO2, cardiopulmonary exercise test), muscle sympathetic nerve activity (MSNA, microneurography), and forearm blood flow (FBF, venous occlusion plethysmography) were measured. We found that peak oxygen consumption peak VO2 and LVEF were significantly reduced in patients with HFrEFCA compared with that of control subjects (P < 0.0001) but similar to those found in patients with HFrEFCA. The sympathetic nerve activity burst frequency and incidence were significantly higher in patients with HFrEFCA than that in control subjects (P < 0.0001). No differences were found between patients with HFrEF and HFrEFCA. Peak VO2 was inversely associated with MSNA burst frequency (r = -0.53, P = 0.002) and burst incidence (r = -0.38, P = 0.01) and directly associated with LVEF (r = 0.71, P < 0.0001). Taken together, we conclude that patients who develop heart failure due to anthracycline- based chemotherapy have sympathetic neural overdrive and reduced exercise capacity. In addition, these physiological changes are similar to those observed in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Co-mutations and KRAS G12C inhibitor efficacy in advanced NSCLC

Author

Negrao, Marcelo V., primary, Araujo, Haniel A., additional, Lamberti, Giuseppe, additional, Cooper, Alissa J., additional, Akhave, Neal S., additional, Zhou, Teng, additional, Delasos, Lukas, additional, Hicks, J Kevin., additional, Aldea, Mihaela, additional, Minuti, Gabriele, additional, Hines, Jacobi, additional, Aredo, Jacqueline V., additional, Dennis, Michael J., additional, Chakrabarti, Turja, additional, Scott, Susan C., additional, Bironzo, Paolo, additional, Scheffler, Matthias, additional, Christopoulos, Petros, additional, Stenzinger, Albrecht, additional, Riess, Jonathan W., additional, Kim, So Yeon, additional, Goldberg, Sarah B., additional, Li, Mingjia, additional, Wang, Qi, additional, Qing, Yun, additional, Ni, Ying, additional, Do, Minh Truong, additional, Lee, Richard, additional, Ricciuti, Biagio, additional, Alessi, Joao Victor., additional, Wang, Jing, additional, Resuli, Blerina, additional, Landi, Lorenza, additional, Tseng, Shu-Chi, additional, Nishino, Mizuki, additional, Digumarthy, Subba R., additional, Rinsurongkawong, Waree, additional, Rinsurongkawong, Vadeerat, additional, Vaporciyan, Ara A, additional, Blumenschein, George R., additional, Zhang, Jianjun, additional, Owen, Dwight H., additional, Blakely, Collin M., additional, Mountzios, Giannis, additional, Shu, Catherine A., additional, Bestvina, Christine M., additional, Garassino, Marina Chiara., additional, Marrone, Kristen A., additional, Gray, Jhanelle E., additional, Patel, Sandip Pravin., additional, Cummings, Amy L., additional, Wakelee, Heather A., additional, Wolf, Juergen, additional, Scagliotti, Giorgio Vittorio., additional, Cappuzzo, Federico, additional, Barlesi, Fabrice, additional, Patil, Pradnya D., additional, Drusbosky, Leylah, additional, Gibbons, Don L., additional, Meric-Bernstam, Funda, additional, Lee, J. Jack, additional, Heymach, John V., additional, Hong, David S., additional, Heist, Rebecca S., additional, Awad, Mark M., additional, and Skoulidis, Ferdinandos, additional

Published
2023
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36. Abstract CT218: A phase II trial of niraparib plus dostarlimab in relapsed small cell lung cancer and other high-grade neuroendocrine carcinomas

Author

Gay, Carl M., primary, Stewart, C. Allison, additional, Frumovitz, Michael, additional, Fujimoto, Junya, additional, xi, Yuann, additional, Wang, Qi, additional, Wang, Runsheng, additional, Novegil, Veronica, additional, Altan, Mehmet, additional, Cascone, Tina, additional, Dasari, Arvind, additional, Elamin, Yasir Y., additional, Fossella, Frank V., additional, Glisson, Bonnie S., additional, Lu, Charles S., additional, Negrao, Marcelo V., additional, Skoulidis, Ferdinandos, additional, Vokes, Natalie, additional, Cardnell, Robert J., additional, Wistuba, Ignacio I., additional, Wang, Jing, additional, Heymach, John V., additional, and Byers, Lauren A., additional

Published
2023
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37. Abstract 113: An atlas of epithelial cell states and plasticity in lung adenocarcinoma

Author

Han, Guangchun, primary, Sinjab, Ansam, additional, Treekitkarnmongkol, Warapen, additional, Rahal, Zahraa, additional, Liu, Yuejiang, additional, Serrano, Alejandra G., additional, Feng, Jiping, additional, Liang, Ke, additional, Khan, Khaja, additional, Lu, Wei, additional, Hernandez, Sharia, additional, Cao, Xuanye, additional, Dai, Enyu, additional, Liu, Yunhe, additional, Pei, Guangsheng, additional, Hu, Jian, additional, Bolanos, Lorena I. Gomez, additional, Parra, Edwin R., additional, Cascone, Tina, additional, Sepesi, Boris, additional, Moghaddam, Seyed Javad, additional, Scheet, Paul, additional, Negrao, Marcelo V., additional, Heymach, John V., additional, Li, Mingyao, additional, Chen, Jichao, additional, Dubinett, Steven M., additional, Fujimoto, Junya, additional, Solis, Luisa M., additional, Wistuba, Ignacio I., additional, Stevenson, Christopher S., additional, Spira, Avrum, additional, Wang, Linghua, additional, and Kadara, Humam, additional

Published
2023
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38. Abstract 4393: Tumor volumetric analysis to correlate disease burden with response to dual immune checkpoint blockade in metastatic NSCLC

Author

Aminu, Muhammad, primary, Vokes, Natalie I., additional, Saad, Maliazurina B., additional, Li, Hui, additional, Hong, Lingzhi, additional, Mohamed, Mohamed S., additional, Boom, John, additional, Chen, Pingjun, additional, Altan, Mehmet, additional, Gandhi, Saumil, additional, Swisher, Stephen, additional, Antonoff, Mara B., additional, Pozadzides, Jenny V., additional, Jr, George Blumenschein, additional, Gibbons, Don L., additional, Cascone, Tina, additional, Elamin, Yasir Y., additional, Le, Xiuning, additional, Negrao, Marcelo V., additional, Skoulidis, Ferdinandos, additional, Tsao, Anne S., additional, Tu, Janet, additional, Lee, J.Jack, additional, Zhang, Jianjun, additional, Heymach, John V., additional, and Wu, Jia, additional

Published
2023
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39. Abstract 3431: Molecular determinants of KRAS p.G12C inhibitor efficacy in advanced NSCLC

Author

Negrao, Marcelo V., primary, Araujo, Haniel A., additional, Lamberti, Giuseppe, additional, Cooper, Alissa J., additional, Zhou, Teng, additional, Akhave, Neal, additional, Delasos, Lukas, additional, Hicks, J Kevin, additional, Aldea, Mihaela, additional, Minuti, Gabriele, additional, Hines, Jacobi, additional, Aredo, Jacqueline V., additional, Dennis, Michael J., additional, Chakrabarti, Turja, additional, Scott, Susan, additional, Bironzo, Paolo, additional, Scheffler, Matthias, additional, Christopoulos, Petros, additional, Kim, So Yeon, additional, Goldberg, Sarah, additional, Ni, Ying, additional, Resuli, Blerina, additional, Landi, Lorenza, additional, Tseng, Shu-Chi, additional, Nishino, Mizuki, additional, Owen, Dwight, additional, Blakely, Collin, additional, Mountzios, Giannis, additional, Shu, Catherine A., additional, Bestvina, Christine, additional, Garassino, Marina, additional, Marrone, Kristen, additional, Gray, Jhanelle, additional, Patel, Sandip Pravin, additional, Cummings, Amy L., additional, Wakelee, Heather A., additional, Wolf, Jurgen, additional, Scagliotti, Giorgio V., additional, Cappuzzo, Federico, additional, Barlesi, Fabrice, additional, Patil, Pradnya, additional, Gibbons, Don L., additional, Meric-Bernstam, Funda, additional, Lee, J Jack, additional, Heymach, John V., additional, Hong, David S., additional, Heist, Rebecca S., additional, Awad, Mark M., additional, and Skoulidis, Ferdinandos, additional

Published
2023
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40. Abstract 964: Genomic and clinical predictors of early disease progression and chemoimmunotherapy benefit in advanced NSCLC

Author

Hong, Lingzhi, primary, Aminu, Muhammad, additional, Lu, Xuetao, additional, Saad, Maliazurina B., additional, Chen, Pingjun, additional, Rinsurongkawong, Waree, additional, Spelman, Amy, additional, Elamin, Yasir Y., additional, Negrao, Marcelo V., additional, Skoulidis, Ferdinandos, additional, Gay, Carl M., additional, Cascone, Tina, additional, Antonoff, Mara B., additional, Sepesi, Boris, additional, Lewis, Jeff, additional, Gibbons, Don L., additional, Vaporciyan, Ara A., additional, Le, Xiuning, additional, Lee, J.Jack, additional, Roy-Chowdhuri, Sinchita, additional, Routbort, Mark J., additional, Heymach, John V., additional, Wu, Jia, additional, Zhang, Jianjun, additional, and Vokes, Natalie I., additional

Published
2023
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41. Abstract 918: Real-world clinical characteristics and treatment (tx) outcomes by co-mutation status in patients (pts) with KRAS G12C-mutated non-small cell lung cancer (NSCLC)

Author

Negrao, Marcelo V., primary, Wu, Wen-Hsing, additional, Lindsay, Colin R., additional, Caparica, Rafael, additional, Prêtre, Vincent, additional, Kang, Yehrim, additional, Caro, Nydia, additional, Farago, Anna, additional, Ye, Fen, additional, and Castro, Gilberto de, additional

Published
2023
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42. Supplementary Figures S1-S7 from STK11/LKB1 Mutations in NSCLC Are Associated with KEAP1/NRF2-Dependent Radiotherapy Resistance Targetable by Glutaminase Inhibition

Author

Sitthideatphaiboon, Piyada, primary, Galan-Cobo, Ana, primary, Negrao, Marcelo V., primary, Qu, Xiao, primary, Poteete, Alissa, primary, Zhang, Fahao, primary, Liu, Diane D., primary, Lewis, Whitney E., primary, Kemp, Haley N., primary, Lewis, Jeff, primary, Rinsurongkawong, Waree, primary, Giri, Uma, primary, Lee, J. Jack, primary, Zhang, Jianjun, primary, Roth, Jack A., primary, Swisher, Stephen, primary, and Heymach, John V., primary

Published
2023
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43. Supplementary Table 7 from Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR-Mutant NSCLC

Author

Le, Xiuning, primary, Puri, Sonam, primary, Negrao, Marcelo V., primary, Nilsson, Monique B., primary, Robichaux, Jacqulyne, primary, Boyle, Theresa, primary, Hicks, J. Kevin, primary, Lovinger, Katherine L., primary, Roarty, Emily, primary, Rinsurongkawong, Waree, primary, Tang, Ming, primary, Sun, Huiying, primary, Elamin, Yasir, primary, Lacerda, Lara C., primary, Lewis, Jeff, primary, Roth, Jack A., primary, Swisher, Stephen G., primary, Lee, J. Jack, primary, William, William N., primary, Glisson, Bonnie S., primary, Zhang, Jianjun, primary, Papadimitrakopoulou, Vassiliki A., primary, Gray, Jhanelle E., primary, and Heymach, John V., primary

Published
2023
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44. Supplementary Table 2 from Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR-Mutant NSCLC

Author

Le, Xiuning, primary, Puri, Sonam, primary, Negrao, Marcelo V., primary, Nilsson, Monique B., primary, Robichaux, Jacqulyne, primary, Boyle, Theresa, primary, Hicks, J. Kevin, primary, Lovinger, Katherine L., primary, Roarty, Emily, primary, Rinsurongkawong, Waree, primary, Tang, Ming, primary, Sun, Huiying, primary, Elamin, Yasir, primary, Lacerda, Lara C., primary, Lewis, Jeff, primary, Roth, Jack A., primary, Swisher, Stephen G., primary, Lee, J. Jack, primary, William, William N., primary, Glisson, Bonnie S., primary, Zhang, Jianjun, primary, Papadimitrakopoulou, Vassiliki A., primary, Gray, Jhanelle E., primary, and Heymach, John V., primary

Published
2023
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45. Supplementary Data from Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR-Mutant NSCLC

Author

Le, Xiuning, primary, Puri, Sonam, primary, Negrao, Marcelo V., primary, Nilsson, Monique B., primary, Robichaux, Jacqulyne, primary, Boyle, Theresa, primary, Hicks, J. Kevin, primary, Lovinger, Katherine L., primary, Roarty, Emily, primary, Rinsurongkawong, Waree, primary, Tang, Ming, primary, Sun, Huiying, primary, Elamin, Yasir, primary, Lacerda, Lara C., primary, Lewis, Jeff, primary, Roth, Jack A., primary, Swisher, Stephen G., primary, Lee, J. Jack, primary, William, William N., primary, Glisson, Bonnie S., primary, Zhang, Jianjun, primary, Papadimitrakopoulou, Vassiliki A., primary, Gray, Jhanelle E., primary, and Heymach, John V., primary

Published
2023
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46. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors

Author

Skoulidis, Ferdinandos, Araujo, Haniel A., Do, Minh Truong, Qian, Yu, Sun, Xin, Cobo, Ana Galan, Le, John T., Montesion, Meagan, Palmer, Rachael, Jahchan, Nadine, Juan, Joseph M., Min, Chengyin, Yu, Yi, Pan, Xuewen, Arbour, Kathryn C., Vokes, Natalie, Schmidt, Stephanie T., Molkentine, David, Owen, Dwight H., Memmott, Regan, Patil, Pradnya D., Marmarelis, Melina E., Awad, Mark M., Murray, Joseph C., Hellyer, Jessica A., Gainor, Justin F., Dimou, Anastasios, Bestvina, Christine M., Shu, Catherine A., Riess, Jonathan W., Blakely, Collin M., Pecot, Chad V., Mezquita, Laura, Tabbó, Fabrizio, Scheffler, Matthias, Digumarthy, Subba, Mooradian, Meghan J., Sacher, Adrian G., Lau, Sally C. M., Saltos, Andreas N., Rotow, Julia, Johnson, Rocio Perez, Liu, Corinne, Stewart, Tyler, Goldberg, Sarah B., Killam, Jonathan, Walther, Zenta, Schalper, Kurt, Davies, Kurtis D., Woodcock, Mark G., Anagnostou, Valsamo, Marrone, Kristen A., Forde, Patrick M., Ricciuti, Biagio, Venkatraman, Deepti, Van Allen, Eliezer M., Cummings, Amy L., Goldman, Jonathan W., Shaish, Hiram, Kier, Melanie, Katz, Sharyn, Aggarwal, Charu, Ni, Ying, Azok, Joseph T., Segal, Jeremy, Ritterhouse, Lauren, Neal, Joel W., Lacroix, Ludovic, Elamin, Yasir Y., Negrao, Marcelo V., Le, Xiuning, Lam, Vincent K., Lewis, Whitney E., Kemp, Haley N., Carter, Brett, Roth, Jack A., Swisher, Stephen, Lee, Richard, Zhou, Teng, Poteete, Alissa, Kong, Yifan, Takehara, Tomohiro, Paula, Alvaro Guimaraes, Parra Cuentas, Edwin R., Behrens, Carmen, Wistuba, Ignacio I., Zhang, Jianjun, Blumenschein, George R., Gay, Carl, Byers, Lauren A., Gibbons, Don L., Tsao, Anne, Lee, J. Jack, Bivona, Trever G., Camidge, D. Ross, Gray, Jhannelle E., Lieghl, Natasha, Levy, Benjamin, Brahmer, Julie R., Garassino, Marina C., Gandara, David R., Garon, Edward B., Rizvi, Naiyer A., Scagliotti, Giorgio Vittorio, Wolf, Jürgen, Planchard, David, Besse, Benjamin, Herbst, Roy S., Wakelee, Heather A., Pennell, Nathan A., Shaw, Alice T., Jänne, Pasi A., Carbone, David P., Hellmann, Matthew D., Rudin, Charles M., Albacker, Lee, Mann, Helen, Zhu, Zhou, Lai, Zhongwu, Stewart, Ross, Peters, Solange, Johnson, Melissa L., Wong, Kwok K., Huang, Alan, Winslow, Monte M., Rosen, Michael J., Winters, Ian P., Papadimitrakopoulou, Vassiliki A., Cascone, Tina, Jewsbury, Philip, and Heymach, John V.

Abstract

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB1,2. Here we show that patients with NSCLC who have mutations in the STK11and/or KEAP1tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial3. Unbiased genetic screens identified loss of both of these tumour suppressor genes as independent drivers of resistance to PD-(L)1 inhibition, and showed that loss of Keap1was the strongest genomic predictor of dual ICB efficacy—a finding that was confirmed in several mouse models of Kras-driven NSCLC. In both mouse models and patients, KEAP1and STK11alterations were associated with an adverse tumour microenvironment, which was characterized by a preponderance of suppressive myeloid cells and the depletion of CD8+cytotoxic T cells, but relative sparing of CD4+effector subsets. Dual ICB potently engaged CD4+effector cells and reprogrammed the tumour myeloid cell compartment towards inducible nitric oxide synthase (iNOS)-expressing tumoricidal phenotypes that—together with CD4+and CD8+T cells—contributed to anti-tumour efficacy. These data support the use of chemo-immunotherapy with dual ICB to mitigate resistance to PD-(L)1 inhibition in patients with NSCLC who have STK11and/or KEAP1alterations.

Published
2024
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48. Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With PD-1/PD-L1 Blockade−Resistant Advanced Non−Small Cell Lung Cancer

Author

Negrao, Marcelo V., primary, Papadimitrakopoulou, Vassiliki A., additional, Price, Andrew C., additional, Tam, Alda L., additional, Furqan, Muhammad, additional, Laroia, Sandeep T., additional, Massarelli, Erminia, additional, Pacheco, Jose, additional, Heymach, John V., additional, Tsao, Anne S., additional, Walker, Gary V., additional, Vora, Lalit, additional, Mauro, David, additional, Kelley, Heather, additional, Wooldridge, James E., additional, Krieg, Arthur M., additional, and Niu, Jiaxin, additional

Published
2022
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49. Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma

Author

Hong, Lingzhi, primary, Lewis, Whitney E., additional, Nilsson, Monique, additional, Patel, Sonia, additional, Varghese, Susan, additional, Rivera, Melvin J., additional, Du, Robyn R., additional, Chen, Pingjun, additional, Kemp, Haley N., additional, Rinsurongkawong, Waree, additional, Heeke, Simon, additional, Spelman, Amy R., additional, Elamin, Yasir Y., additional, Negrao, Marcelo V., additional, Sepesi, Boris, additional, Gibbons, Don L., additional, Lee, J. Jack, additional, Wu, Jia, additional, Vokes, Natalie I., additional, Heymach, John V., additional, Zhang, Jianjun, additional, and Le, Xiuning, additional

Published
2022
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50. Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation

Author

Jänne, Pasi A., primary, Riely, Gregory J., additional, Gadgeel, Shirish M., additional, Heist, Rebecca S., additional, Ou, Sai-Hong I., additional, Pacheco, Jose M., additional, Johnson, Melissa L., additional, Sabari, Joshua K., additional, Leventakos, Konstantinos, additional, Yau, Edwin, additional, Bazhenova, Lyudmila, additional, Negrao, Marcelo V., additional, Pennell, Nathan A., additional, Zhang, Jun, additional, Anderes, Kenna, additional, Der-Torossian, Hirak, additional, Kheoh, Thian, additional, Velastegui, Karen, additional, Yan, Xiaohong, additional, Christensen, James G., additional, Chao, Richard C., additional, and Spira, Alexander I., additional

Published
2022
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