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1. Automated real-world data integration improves cancer outcome prediction

Author

Jee, Justin, Fong, Christopher, Pichotta, Karl, Tran, Thinh Ngoc, Luthra, Anisha, Waters, Michele, Fu, Chenlian, Altoe, Mirella, Liu, Si-Yang, Maron, Steven B., Ahmed, Mehnaj, Kim, Susie, Pirun, Mono, Chatila, Walid K., de Bruijn, Ino, Pasha, Arfath, Kundra, Ritika, Gross, Benjamin, Mastrogiacomo, Brooke, Aprati, Tyler J., Liu, David, Gao, JianJiong, Capelletti, Marzia, Pekala, Kelly, Loudon, Lisa, Perry, Maria, Bandlamudi, Chaitanya, Donoghue, Mark, Satravada, Baby Anusha, Martin, Axel, Shen, Ronglai, Chen, Yuan, Brannon, A. Rose, Chang, Jason, Braunstein, Lior, Li, Anyi, Safonov, Anton, Stonestrom, Aaron, Sanchez-Vela, Pablo, Wilhelm, Clare, Robson, Mark, Scher, Howard, Ladanyi, Marc, Reis-Filho, Jorge S., Solit, David B., Jones, David R., Gomez, Daniel, Yu, Helena, Chakravarty, Debyani, Yaeger, Rona, Abida, Wassim, Park, Wungki, O’Reilly, Eileen M., Garcia-Aguilar, Julio, Socci, Nicholas, Sanchez-Vega, Francisco, Carrot-Zhang, Jian, Stetson, Peter D., Levine, Ross, Rudin, Charles M., Berger, Michael F., Shah, Sohrab P., Schrag, Deborah, Razavi, Pedram, Kehl, Kenneth L., Li, Bob T., Riely, Gregory J., and Schultz, Nikolaus

Published
2024
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3. Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors

Author

Hickman, Richard A., Miller, Alexandra M., Holle, Bridget M., Jee, Justin, Liu, Si-Yang, Ross, Dara, Yu, Helena, Riely, Gregory J., Ombres, Christina, Gewirtz, Alexandra N., Reiner, Anne S., Nandakumar, Subhiksha, Price, Adam, Kaley, Thomas J., Graham, Maya S., Vanderbilt, Chad, Rana, Satshil, Hill, Katherine, Chabot, Kiana, Campos, Carl, Nafa, Khedoudja, Shukla, Neerav, Karajannis, Matthias, Li, Bob, Berger, Michael, Ladanyi, Marc, Pentsova, Elena, Boire, Adrienne, Brannon, A. Rose, Bale, Tejus, Mellinghoff, Ingo K., and Arcila, Maria E.

Published
2024
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4. CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Author

Quintanal-Villalonga, Alvaro, Kawasaki, Kenta, Redin, Esther, Uddin, Fathema, Rakhade, Swanand, Durani, Vidushi, Sabet, Amin, Shafer, Moniquetta, Karthaus, Wouter R., Zaidi, Samir, Zhan, Yingqian A., Manoj, Parvathy, Sridhar, Harsha, Kinyua, Dennis, Zhong, Hong, Mello, Barbara P., Ciampricotti, Metamia, Bhanot, Umesh K., Linkov, Irina, Qiu, Juan, Patel, Radhika A., Morrissey, Colm, Mehta, Sanjoy, Barnes, Jesse, Haffner, Michael C., Socci, Nicholas D., Koche, Richard P., de Stanchina, Elisa, Molina-Pinelo, Sonia, Salehi, Sohrab, Yu, Helena A., Chan, Joseph M., and Rudin, Charles M.

Published
2024
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5. The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

Author

Caswell, Deborah R, Gui, Philippe, Mayekar, Manasi K, Law, Emily K, Pich, Oriol, Bailey, Chris, Boumelha, Jesse, Kerr, D Lucas, Blakely, Collin M, Manabe, Tadashi, Martinez-Ruiz, Carlos, Bakker, Bjorn, De Dios Palomino Villcas, Juan, I. Vokes, Natalie, Dietzen, Michelle, Angelova, Mihaela, Gini, Beatrice, Tamaki, Whitney, Allegakoen, Paul, Wu, Wei, Humpton, Timothy J, Hill, William, Tomaschko, Mona, Lu, Wei-Ting, Haderk, Franziska, Al Bakir, Maise, Nagano, Ai, Gimeno-Valiente, Francisco, de Carné Trécesson, Sophie, Vendramin, Roberto, Barbè, Vittorio, Mugabo, Miriam, Weeden, Clare E, Rowan, Andrew, McCoach, Caroline E, Almeida, Bruna, Green, Mary, Gomez, Carlos, Nanjo, Shigeki, Barbosa, Dora, Moore, Chris, Przewrocka, Joanna, Black, James RM, Grönroos, Eva, Suarez-Bonnet, Alejandro, Priestnall, Simon L, Zverev, Caroline, Lighterness, Scott, Cormack, James, Olivas, Victor, Cech, Lauren, Andrews, Trisha, Rule, Brandon, Jiao, Yuwei, Zhang, Xinzhu, Ashford, Paul, Durfee, Cameron, Venkatesan, Subramanian, Temiz, Nuri Alpay, Tan, Lisa, Larson, Lindsay K, Argyris, Prokopios P, Brown, William L, Yu, Elizabeth A, Rotow, Julia K, Guha, Udayan, Roper, Nitin, Yu, Johnny, Vogel, Rachel I, Thomas, Nicholas J, Marra, Antonio, Selenica, Pier, Yu, Helena, Bakhoum, Samuel F, Chew, Su Kit, Reis-Filho, Jorge S, Jamal-Hanjani, Mariam, Vousden, Karen H, McGranahan, Nicholas, Van Allen, Eliezer M, Kanu, Nnennaya, Harris, Reuben S, Downward, Julian, Bivona, Trever G, and Swanton, Charles

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Cancer, Lung Cancer, Women's Health, Biotechnology, Lung, 5.1 Pharmaceuticals, Humans, Animals, Mice, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Mutation, Up-Regulation, ErbB Receptors, Cytidine Deaminase, Minor Histocompatibility Antigens, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

Published
2024

6. Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study

Author

Nassar, Amin H., Kim, So Yeon, Aredo, Jacqueline V., Feng, Jamie, Shepherd, Frances, Xu, Chao, Kaldas, David, Gray, Jhanelle E., Dilling, Thomas J., Neal, Joel W., Wakelee, Heather A., Liu, Yufei, Lin, Steven H., Abuali, Tariq, Amini, Arya, Nie, Yunan, Patil, Tejas, Lobachov, Anastasiya, Bar, Jair, Fitzgerald, Bailey, Fujiwara, Yu, Marron, Thomas U., Thummalapalli, Rohit, Yu, Helena, Owen, Dwight H., Sharp, John, Farid, Saira, Rocha, Pedro, Arriola, Edurne, D’Aiello, Angelica, Cheng, Haiying, Whitaker, Ryan, Parikh, Kaushal, Ashara, Yash, Chen, Luxi, Sankar, Kamya, Harris, Jeremy P., Nagasaka, Misako, Ayanambakkam, Adanma, Velazquez, Ana I., Ragavan, Meera, Lin, Jessica J., Piotrowska, Zofia, Wilgucki, Molly, Reuss, Joshua, Luders, Heike, Grohe, Christian, Baena Espinar, Javier, Feiner, Ella, Punekar, Salman R., Gupta, Shruti, Leal, Ticiana, Kwiatkowski, David J., Mak, Raymond H., Adib, Elio, Naqash, Abdul Rafeh, and Goldberg, Sarah B.

Published
2024
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7. Small-molecule targeted therapies induce dependence on DNA double-strand break repair in residual tumor cells

Author

Ali, Moiez, Lu, Min, Ang, Hazel Xiaohui, Soderquist, Ryan S, Eyler, Christine E, Hutchinson, Haley M, Glass, Carolyn, Bassil, Christopher F, Lopez, Omar M, Kerr, D Lucas, Falcon, Christina J, Yu, Helena A, Hata, Aaron N, Blakely, Collin M, McCoach, Caroline E, Bivona, Trever G, and Wood, Kris C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Lung Cancer, Cancer, Lung, Women's Health, Rare Diseases, Neurosciences, Genetics, Ataxia Telangiectasia, Neurodegenerative, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Animals, Carcinoma, Non-Small-Cell Lung, DNA, DNA Repair, Humans, Lung Neoplasms, Mice, Neoplasm, Residual, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Residual cancer cells that survive drug treatments with targeted therapies act as a reservoir from which eventual resistant disease emerges. Although there is great interest in therapeutically targeting residual cells, efforts are hampered by our limited knowledge of the vulnerabilities existing in this cell state. Here, we report that diverse oncogene-targeted therapies, including inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), KRAS, and BRAF, induce DNA double-strand breaks and, consequently, ataxia-telangiectasia mutated (ATM)-dependent DNA repair in oncogene-matched residual tumor cells. This DNA damage response, observed in cell lines, mouse xenograft models, and human patients, is driven by a pathway involving the activation of caspases 3 and 7 and the downstream caspase-activated deoxyribonuclease (CAD). CAD is, in turn, activated through caspase-mediated degradation of its endogenous inhibitor, ICAD. In models of EGFR mutant non-small cell lung cancer (NSCLC), tumor cells that survive treatment with small-molecule EGFR-targeted therapies are thus synthetically dependent on ATM, and combined treatment with an ATM kinase inhibitor eradicates these cells in vivo. This led to more penetrant and durable responses in EGFR mutant NSCLC mouse xenograft models, including those derived from both established cell lines and patient tumors. Last, we found that rare patients with EGFR mutant NSCLC harboring co-occurring, loss-of-function mutations in ATM exhibit extended progression-free survival on first generation EGFR inhibitor therapy relative to patients with EGFR mutant NSCLC lacking deleterious ATM mutations. Together, these findings establish a rationale for the mechanism-based integration of ATM inhibitors alongside existing targeted therapies.

Published
2022

9. Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor–Resistant, EGFR-Mutated Non–Small Cell Lung CancerHER3-DXd in EGFR TKI–Resistant EGFR-Mutated NSCLC

Author

Jänne, Pasi A, Baik, Christina, Su, Wu-Chou, Johnson, Melissa L, Hayashi, Hidetoshi, Nishio, Makoto, Kim, Dong-Wan, Koczywas, Marianna, Gold, Kathryn A, Steuer, Conor E, Murakami, Haruyasu, Yang, James Chih-Hsin, Kim, Sang-We, Vigliotti, Michele, Shi, Rong, Qi, Zhenhao, Qiu, Yang, Zhao, Lihui, Sternberg, David, Yu, Channing, and Yu, Helena A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Lung, Lung Cancer, Clinical Research, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Aged, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Camptothecin, Carcinoma, Non-Small-Cell Lung, Disease-Free Survival, Dose-Response Relationship, Drug, ErbB Receptors, Female, Humans, Infusions, Intravenous, Lung Neoplasms, Male, Middle Aged, Neoplasm Metastasis, Treatment Outcome, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but is not a known mechanism of resistance to EGFR inhibitors. HER3-DXd is an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor (TKI) therapy. Among 57 patients receiving HER3-DXd 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1) was 39% [95% confidence interval (CI), 26.0-52.4], and median progression-free survival was 8.2 (95% CI, 4.4-8.3) months. Responses were observed in patients with known and unknown EGFR TKI resistance mechanisms. Clinical activity was observed across a broad range of HER3 membrane expression. The most common grade ≥3 treatment-emergent adverse events were hematologic toxicities. HER3-DXd has clinical activity in EGFR TKI-resistant cancers independent of resistance mechanisms, providing an approach to treat a broad range of drug-resistant cancers. SIGNIFICANCE: In metastatic EGFR-mutated NSCLC, after disease progression on EGFR TKI therapy, treatment approaches include genotype-directed therapy targeting a known resistance mechanism or chemotherapy. HER3-DXd demonstrated clinical activity spanning known and unknown EGFR TKI resistance mechanisms. HER3-DXd could present a future treatment option agnostic to the EGFR TKI resistance mechanism.See related commentary by Lim et al., p. 16.This article is highlighted in the In This Issue feature, p. 1.

Published
2022

12. Phase II Study of Osimertinib in Patients With Epidermal Growth Factor Receptor Mutations: Results From the NCI-MATCH ECOG-ACRIN (EAY131) Trial Subprotocol E

Author

Chen, Monica F., Song, Zihe, Yu, Helena A., Sequist, Lecia V., Lovly, Christine M., Mitchell, Edith P., Moscow, Jeffrey A., Gray, Robert J., Wang, Victoria, McShane, Lisa M., Rubinstein, Larry V., Patton, David R., Williams, P. Mickey, Hamilton, Stanley R., Umemura, Yoshie, Tricoli, James V., Conley, Barbara A., Arteaga, Carlos L., Harris, Lyndsay N., OʼDwyer, Peter J., Chen, Alice P., and Flaherty, Keith T.

Published
2024
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14. Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer

Author

Jee, Justin, Lebow, Emily S., Yeh, Randy, Das, Jeeban P., Namakydoust, Azadeh, Paik, Paul K., Chaft, Jamie E., Jayakumaran, Gowtham, Rose Brannon, A., Benayed, Ryma, Zehir, Ahmet, Donoghue, Mark, Schultz, Nikolaus, Chakravarty, Debyani, Kundra, Ritika, Madupuri, Ramyasree, Murciano-Goroff, Yonina R., Tu, Hai-Yan, Xu, Chong-Rui, Martinez, Andrés, Wilhelm, Clare, Galle, Jesse, Daly, Bobby, Yu, Helena A., Offin, Michael, Hellmann, Matthew D., Lito, Piro, Arbour, Kathryn C., Zauderer, Marjorie G., Kris, Mark G., Ng, Kenneth K., Eng, Juliana, Preeshagul, Isabel, Victoria Lai, W., Fiore, John J., Iqbal, Afsheen, Molena, Daniela, Rocco, Gaetano, Park, Bernard J., Lim, Lee P., Li, Mark, Tong-Li, Candace, De Silva, Madhawa, Chan, David L., Diakos, Connie I., Itchins, Malinda, Clarke, Stephen, Pavlakis, Nick, Lee, Adrian, Rekhtman, Natasha, Chang, Jason, Travis, William D., Riely, Gregory J., Solit, David B., Gonen, Mithat, Rusch, Valerie W., Rimner, Andreas, Gomez, Daniel, Drilon, Alexander, Scher, Howard I., Shah, Sohrab P., Berger, Michael F., Arcila, Maria E., Ladanyi, Marc, Levine, Ross L., Shen, Ronglai, Razavi, Pedram, Reis-Filho, Jorge S., Jones, David R., Rudin, Charles M., Isbell, James M., and Li, Bob T.

Published
2022
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17. Immune biomarkers and response to checkpoint inhibition of BRAFV600 and BRAF non-V600 altered lung cancers

Author

Murciano-Goroff, Yonina R., Pak, Terry, Mondaca, Sebastian, Flynn, Jessica R., Montecalvo, Joseph, Rekhtman, Natasha, Halpenny, Darragh, Plodkowski, Andrew J., Wu, Stephanie L., Kris, Mark G., Paik, Paul K., Riely, Gregory J., Yu, Helena A., Rudin, Charles M., Hellmann, Matthew D., Land, Josiah D., Buie, Larry W., Heller, Glenn, Lito, Piro, Yaeger, Rona, Drilon, Alexander, Liu, Dazhi, Li, Bob T., and Offin, Michael

Published
2022
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19. Signatures of early plasticity in the histological transformation of lung cancer.

Author

Rakhade, Swanand, primary, Chen, Monica F, additional, Quintanal-Villalonga, Alvaro, additional, Sabet, Amin, additional, Manoj, Parvathy, additional, Chaudhary, Ojasvi, additional, Xu, Tianhao, additional, Masilionis, Ignas, additional, Falcon, Christina J., additional, Egger, Jacklynn V., additional, Nawy, Tal, additional, Mazutis, Linas, additional, Chaligne, Ronan, additional, Yu, Helena Alexandra, additional, Pe'er, Dana, additional, Rudin, Charles M., additional, and Chan, Joseph Minhow, additional

Published
2024
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21. Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis

Author

Tanaka, Kosuke, Yu, Helena A., Yang, Shaoyuan, Han, Song, Selcuklu, S. Duygu, Kim, Kwanghee, Ramani, Shriram, Ganesan, Yogesh Tengarai, Moyer, Allison, Sinha, Sonali, Xie, Yuchen, Ishizawa, Kota, Osmanbeyoglu, Hatice U., Lyu, Yang, Roper, Nitin, Guha, Udayan, Rudin, Charles M., Kris, Mark G., Hsieh, James J., and Cheng, Emily H.

Published
2021
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22. Clinical Experience of Cerebrospinal Fluid–Based Liquid Biopsy Demonstrates Superiority of Cell-Free DNA over Cell Pellet Genomic DNA for Molecular Profiling

Author

Bale, Tejus A., Yang, Soo-Ryum, Solomon, James P., Nafa, Khedoudja, Middha, Sumit, Casanova, Jacklyn, Sadowska, Justyna, Skakodub, Anna, Ahmad, Hamza, Yu, Helena A., Riely, Greg J., Kris, Mark G., Chandarlapaty, Sarat, Rosenblum, Marc K., Gavrilovic, Igor, Karajannis, Matthias A., Pentsova, Elena, Miller, Alexandra, Boire, Adrienne, Mellinghoff, Ingo, Berger, Michael F., Zehir, Ahmet, Ladanyi, Marc, Benayed, Ryma, and Arcila, Maria E.

Published
2021
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23. Consolidation ALK Tyrosine Kinase Inhibitors Versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK-Positive NSCLC

Author

Nassar, Amin H., Jayakrishnan, Ritujith, Feng, Jamie, Shepherd, Frances, Adib, Elio, Cheung, Justin M., Lin, Jessica J., Liu, Yufei, Lin, Steven H., Parikh, Kaushal, Sridhar, Arthi, Shakya, Purnima, Dilling, Thomas J., Kaldas, David, Gray, Jhanelle E., Lobachov, Anastasiya, Bar, Jair, Luders, Heike, Grohe, Christian, Gupta, Shruti, Leal, Ticiana, Fitzgerald, Bailey, Crowley, Fionnuala, Fujiwara, Yu, Marron, Thomas U., Wilgucki, Molly, Reuss, Joshua, Chen, Luxi, Sankar, Kamya, Aredo, Jacqueline V., Neal, Joel W., Wakelee, Heather A., Thummalapalli, Rohit, Yu, Helena, Whitaker, Ryan, Velazquez, Ana, Ragavan, Meera, Cortellini, Alessio, Kwiatkowski, David J., Naqash, Abdul Rafeh, Goldberg, Sarah B., and Kim, So Yeon

Abstract

Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Published
2025
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25. 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

Author

Sequist, Lecia V, Han, Ji-Youn, Ahn, Myung-Ju, Cho, Byoung Chul, Yu, Helena, Kim, Sang-We, Yang, James Chih-Hsin, Lee, Jong Seok, Su, Wu-Chou, Kowalski, Dariusz, Orlov, Sergey, Cantarini, Mireille, Verheijen, Remy B, Mellemgaard, Anders, Ottesen, Lone, Frewer, Paul, Ou, Xiaoling, and Oxnard, Geoffrey

Published
2020
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28. Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation

Author

Quintanal-Villalonga, Alvaro, Taniguchi, Hirokazu, Zhan, Yingqian A., Hasan, Maysun M., Chavan, Shweta S., Meng, Fanli, Uddin, Fathema, Allaj, Viola, Manoj, Parvathy, Shah, Nisargbhai S., Chan, Joseph M., Ciampricotti, Metamia, Chow, Andrew, Offin, Michael, Ray-Kirton, Jordana, Egger, Jacklynn D., Bhanot, Umesh K., Linkov, Irina, Asher, Marina, Roehrl, Michael H., Ventura, Katia, Qiu, Juan, de Stanchina, Elisa, Chang, Jason C., Rekhtman, Natasha, Houck-Loomis, Brian, Koche, Richard P., Yu, Helena A., Sen, Triparna, and Rudin, Charles M.

Published
2021
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30. Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS

Author

Rose Brannon, A., Jayakumaran, Gowtham, Diosdado, Monica, Patel, Juber, Razumova, Anna, Hu, Yu, Meng, Fanli, Haque, Mohammad, Sadowska, Justyna, Murphy, Brian J., Baldi, Tessara, Johnson, Ian, Ptashkin, Ryan, Hasan, Maysun, Srinivasan, Preethi, Rema, Anoop Balakrishnan, Rijo, Ivelise, Agarunov, Aaron, Won, Helen, Perera, Dilmi, Brown, David N., Samoila, Aliaksandra, Jing, Xiaohong, Gedvilaite, Erika, Yang, Julie L., Stephens, Dennis P., Dix, Jenna-Marie, DeGroat, Nicole, Nafa, Khedoudja, Syed, Aijazuddin, Li, Alan, Lebow, Emily S., Bowman, Anita S., Ferguson, Donna C., Liu, Ying, Mata, Douglas A., Sharma, Rohit, Yang, Soo-Ryum, Bale, Tejus, Benhamida, Jamal K., Chang, Jason C., Dogan, Snjezana, Hameed, Meera R., Hechtman, Jaclyn F., Moung, Christine, Ross, Dara S., Vakiani, Efsevia, Vanderbilt, Chad M., Yao, JinJuan, Razavi, Pedram, Smyth, Lillian M., Chandarlapaty, Sarat, Iyer, Gopa, Abida, Wassim, Harding, James J., Krantz, Benjamin, O’Reilly, Eileen, Yu, Helena A., Li, Bob T., Rudin, Charles M., Diaz, Luis, Solit, David B., Arcila, Maria E., Ladanyi, Marc, Loomis, Brian, Tsui, Dana, Berger, Michael F., Zehir, Ahmet, and Benayed, Ryma

Published
2021
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31. Concurrent RB1 and TP53 Alterations Define a Subset of EGFR-Mutant Lung Cancers at risk for Histologic Transformation and Inferior Clinical Outcomes

Author

Offin, Michael, Chan, Joseph M., Tenet, Megan, Rizvi, Hira A., Shen, Ronglai, Riely, Gregory J., Rekhtman, Natasha, Daneshbod, Yahya, Quintanal-Villalonga, Alvaro, Penson, Alexander, Hellmann, Matthew D., Arcila, Maria E., Ladanyi, Marc, Pe’er, Dana, Kris, Mark G., Rudin, Charles M., and Yu, Helena A.

Published
2019
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33. Consolidation Osimertinib versus Durvalumab versus Observation following Concurrent Chemoradiation in Unresectable EGFR-Mutant Non-Small-Cell Lung Cancer: A Multicenter Retrospective Cohort Study

Author

Nassar, Amin H., primary, Kim, So Yeon, additional, Aredo, Jacqueline V., additional, Feng, Jamie, additional, Shepherd, Frances, additional, Xu, Chao, additional, Kaldas, David, additional, Gray, Jhanelle E., additional, Dilling, Thomas J., additional, Neal, Joel W., additional, Wakelee, Heather A., additional, Liu, Yufei, additional, Lin, Steven H., additional, Abuali, Tariq, additional, Amini, Arya, additional, Nie, Yunan, additional, Patil, Tejas, additional, Lobachov, Anastasiya, additional, Bar, Jair, additional, Fitzgerald, Bailey, additional, Fujiwara, Yu, additional, Marron, Thomas U., additional, Thummalapalli, Rohit, additional, Yu, Helena, additional, Owen, Dwight H., additional, Sharp, John, additional, Farid, Saira, additional, Rocha, Pedro, additional, Arriola, Edurne, additional, D’Aiello, Angelica, additional, Cheng, Haiying, additional, Whitaker, Ryan, additional, Parikh, Kaushal, additional, Ashara, Yash, additional, Chen, Luxi, additional, Sankar, Kamya, additional, Harris, Jeremy P., additional, Nagasaka, Misako, additional, Ayanambakkam, Adanma, additional, Manana, Ana I., additional, Ragavan, Meera, additional, Lin, Jessica J., additional, Piotrowska, Zofia, additional, Wilgucki, Molly, additional, Reuss, Joshua, additional, Luders, Heike, additional, Grohe, Christian, additional, Espinar, Javier Baena, additional, Feiner, Ella, additional, Punekar, Salman R., additional, Gupta, Shruti, additional, Leal, Ticiana, additional, Kwiatkowski, David J., additional, Mak, Raymond H., additional, Adib, Elio, additional, Naqash, Abdul Rafeh, additional, and Goldberg, Sarah B., additional

Published
2024
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35. HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor–Mutated Non–Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy

Author

Yu, Helena A., primary, Goto, Yasushi, additional, Hayashi, Hidetoshi, additional, Felip, Enriqueta, additional, Chih-Hsin Yang, James, additional, Reck, Martin, additional, Yoh, Kiyotaka, additional, Lee, Se-Hoon, additional, Paz-Ares, Luis, additional, Besse, Benjamin, additional, Bironzo, Paolo, additional, Kim, Dong-Wan, additional, Johnson, Melissa L., additional, Wu, Yi-Long, additional, John, Thomas, additional, Kao, Steven, additional, Kozuki, Toshiyuki, additional, Massarelli, Erminia, additional, Patel, Jyoti, additional, Smit, Egbert, additional, Reckamp, Karen L., additional, Dong, Qian, additional, Shrestha, Pomy, additional, Fan, Pang-Dian, additional, Patel, Parul, additional, Sporchia, Andrea, additional, Sternberg, David W., additional, Sellami, Dalila, additional, and Jänne, Pasi A., additional

Published
2023
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36. YES1 amplification is a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics

Author

Fan, Pang-Dian, Narzisi, Giuseppe, Jayaprakash, Anitha D., Venturini, Elisa, Robine, Nicolas, Smibert, Peter, Germer, Soren, Yu, Helena A., Jordan, Emmet J., Paik, Paul K., Janjigian, Yelena Y., Chaft, Jamie E., Wang, Lu, Jungbluth, Achim A., Middha, Sumit, Spraggon, Lee, Qiao, Huan, Lovly, Christine M., Kris, Mark G., Riely, Gregory J., Politi, Katerina, Varmus, Harold, and Ladanyi, Marc

Published
2018

40. PS1-2 First report of cohort 3 and mature survival data from the U31402-A-U102 study of HER3-DXd in EGFR-mutated NSCLC

Author

Hayashi, Hidetoshi, primary, Yu, Helena A., additional, Baik, Christina, additional, Kim, Dong-Wan, additional, Johnson, Melissa L., additional, Nishio, Makoto, additional, Chih-Hsin Yang, James, additional, Su, Wu-Chou, additional, Gold, Kathryn A., additional, Koczywas, Marianna, additional, Smit, Egbert F., additional, Steuer, Conor, additional, Felip, Enriqueta, additional, Murakami, Haruyasu, additional, Kim, Sang-We, additional, Kim, Ben, additional, Su, Xin, additional, Tanaka, Yoshimi, additional, Fan, Pang-Dian, additional, and Cantero, Frederique, additional

Published
2023
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41. Safety, Tolerability, and Antitumor Activity of Zipalertinib Among Patients With Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 20 Insertions

Author

Piotrowska, Zofia, primary, Tan, Daniel Shao-Weng, additional, Smit, Egbert F., additional, Spira, Alexander I., additional, Soo, Ross A., additional, Nguyen, Danny, additional, Lee, Victor Ho-Fun, additional, Yang, James Chih-Hsin, additional, Velcheti, Vamsidhar, additional, Wrangle, John M., additional, Socinski, Mark A., additional, Koczywas, Marianna, additional, Janik, John E., additional, Jones, Jeffrey, additional, and Yu, Helena Alexandra, additional

Published
2023
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47. HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation EGFR TKI.

Author

Mok, Tony, Jänne, Pasi A, Nishio, Makoto, Novello, Silvia, Reck, Martin, Steuer, Conor, Wu, Yi-Long, Fougeray, Ronan, Fan, Pang-Dian, Meng, Jie, Sternberg, David W, Esker, Stephen, and Yu, Helena A

Abstract

After disease progression on EGFR tyrosine kinase inhibitor (TKI) therapy, patients with EGFR-mutated NSCLC who are then treated with platinum-based chemotherapy (PBC) obtain only limited clinical benefit with transient responses. Therapies with greater efficacy and tolerable safety profiles are needed in this setting. The receptor tyrosine kinase HER3 is widely expressed in NSCLC, and increased expression is associated with poor treatment outcomes. In the U31402-A-U102 phase I trial, HER3-DXd showed promising antitumor activity with manageable safety in heavily pre-treated patients with EGFR-mutated NSCLC across a range of tumor HER3 expression levels and EGFR TKI resistance mechanisms. HERTHENA-Lung02 is the first phase III trial to evaluate the safety and efficacy of HER3-DXd versus PBC in patients with progression on a third-generation EGFR TKI. Clinical Trial Registration:NCT05338970 (clinicaltrials.gov); 2021-005879-40 (EudraCT Number). In some patients with non-small-cell lung cancer, changes (or mutations) in the DNA sequence can alter a protein called EGFR and allow tumors to grow and survive. Drugs called EGFR tyrosine kinase inhibitors (EGFR TKIs for short) are used to treat these tumors by interfering with the abnormal EGFR protein. Treatment with these drugs can work well at first, but some tumors never respond, and for tumors that do respond, the cancer eventually becomes resistant to the EGFR TKI and the drug stops working. Platinum-based chemotherapy is often prescribed after an EGFR TKI stops working; however, platinum-based chemotherapy can provide only temporary control of the tumor growth. Most patients with non-small-cell lung cancer have a protein called HER3 on the surface of their tumor cells. A new drug candidate called patritumab deruxtecan (HER3-DXd) finds tumor cells and attaches to the HER3 protein on their surface. HER3-DXd then moves inside the cancer cells, where a novel antitumor payload is released and kills the tumor cells. This article describes the phase III clinical trial HERTHENA-Lung02 (NCT05338970) that compares the benefit of HER3-DXd to platinum-based chemotherapy for patients who have non-small-cell lung cancer with the abnormal EGFR protein and whose disease stopped responding or never responded to EGFR TKI therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Supplementary Table S6 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers

Author

Rotow, Julia, primary, Patel, Jyoti D., primary, Hanley, Matthew P., primary, Yu, Helena, primary, Awad, Mark, primary, Goldman, Jonathan W., primary, Nechushtan, Hovav, primary, Scheffler, Matthias, primary, Kuo, Chih-Hsi S., primary, Rajappa, Senthil, primary, Harada, Guilherme, primary, Clifford, Sarah, primary, Santucci, Alison, primary, Silva, Laura, primary, Tupper, Rebecca, primary, Oxnard, Geoffrey R., primary, Kherani, Jennifer, primary, and Drilon, Alexander, primary

Published
2023
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49. Supplementary Figure S2 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers

Author

Rotow, Julia, primary, Patel, Jyoti D., primary, Hanley, Matthew P., primary, Yu, Helena, primary, Awad, Mark, primary, Goldman, Jonathan W., primary, Nechushtan, Hovav, primary, Scheffler, Matthias, primary, Kuo, Chih-Hsi S., primary, Rajappa, Senthil, primary, Harada, Guilherme, primary, Clifford, Sarah, primary, Santucci, Alison, primary, Silva, Laura, primary, Tupper, Rebecca, primary, Oxnard, Geoffrey R., primary, Kherani, Jennifer, primary, and Drilon, Alexander, primary

Published
2023
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50. Data from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers

Author

Rotow, Julia, primary, Patel, Jyoti D., primary, Hanley, Matthew P., primary, Yu, Helena, primary, Awad, Mark, primary, Goldman, Jonathan W., primary, Nechushtan, Hovav, primary, Scheffler, Matthias, primary, Kuo, Chih-Hsi S., primary, Rajappa, Senthil, primary, Harada, Guilherme, primary, Clifford, Sarah, primary, Santucci, Alison, primary, Silva, Laura, primary, Tupper, Rebecca, primary, Oxnard, Geoffrey R., primary, Kherani, Jennifer, primary, and Drilon, Alexander, primary

Published
2023
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