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2. Tissue-specific thresholds of mutation burden associated with anti-PD-1/L1 therapy benefit and prognosis in microsatellite-stable cancers

Author

Muquith, Maishara, Espinoza, Magdalena, Elliott, Andrew, Xiu, Joanne, Seeber, Andreas, El-Deiry, Wafik, Antonarakis, Emmanuel S., Graff, Stephanie L., Hall, Michael J., Borghaei, Hossein, Hoon, Dave S. B., Liu, Stephen V., Ma, Patrick C., McKay, Rana R., Wise-Draper, Trisha, Marshall, John, Sledge, George W., Spetzler, David, Zhu, Hao, and Hsiehchen, David

Published
2024
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3. Impact of gender and mutational differences in hormone receptor expressing non-small cell lung cancer

Author

Hsu, Robert, Chen, Denaly, Xia, Bing, Feldman, Rebecca, Cozen, Wendy, Raez, Luis E, Borghaei, Hossein, Kim, Chul, Nagasaka, Misako, Mamdani, Hirva, Vanderwalde, Ari M, Lopes, Gilberto, Socinski, Mark A, Wozniak, Antoinette J, Spira, Alexander I, Liu, Stephen V, and Nieva, Jorge J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Estrogen, Cancer, Lung, Lung Cancer, Genetics, Good Health and Well Being, gender, hormone receptor, mutational differences, non-small cell lung cancer, disparities, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundThe incidence of lung cancer in the US has been decreasing but a bigger decline has been observed in men despite similar declines in tobacco use between men and women. Multiple theories have been proposed, including exposure to exogenous estrogens. Our study seeks to understand the relationship between hormone receptors (HR), gender, and the genomic landscape of non-small lung cancer (NSCLC).Methods3,256 NSCLC tumor samples submitted for molecular profiling between 2013-2018 were retrospectively identified and assessed for HR expression. Hormone receptor (HR+) was defined as ≥ 1% nuclear staining of estrogen receptor-alpha (ER-a) or progesterone receptor (PR) by immunohistochemistry. DNA sequencing by NGS included cases sequenced by the Illumina MiSeq hot spot 47 gene panel (n=2753) and Illumina NextSeq 592 gene panel (n=503). An adjusted p-value (q-value)

Published
2023

6. A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors

Author

Zibelman, Matthew, MacFarlane, IV, Alexander W., Costello, Kimberly, McGowan, Thomas, O’Neill, John, Kokate, Rutika, Borghaei, Hossein, Denlinger, Crystal S., Dotan, Efrat, Geynisman, Daniel M., Jain, Angela, Martin, Lainie, Obeid, Elias, Devarajan, Karthik, Ruth, Karen, Alpaugh, R. Katherine, Dulaimi, Essel Al-Saleem, Cukierman, Edna, Einarson, Margret, Campbell, Kerry S., and Plimack, Elizabeth R.

Published
2023
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7. A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors

Author

Beckermann, Kathryn E., Bestvina, Christine M., El Osta, Badi, Sanborn, Rachel E., Borghaei, Hossein, Lammers, Philip Edward, Selvaggi, Giovanni, Whisenant, Jennifer G., Heimann-Nichols, Ellen, Berry, Lynne, Hsu, Chih-Yuan, Shyr, Yu, Horn, Leora, and Wakelee, Heather

Published
2024
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9. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

Author

Abdel-Karim, Isam, Abdelsalam, Mahmoud, Addeo, Alfredo, Aguado, Carlos, Alexander, Patrick, Alt, Jürgen, Azzi, Georges, Balaraman, Rama, Biesma, Bonne, Blackhall, Fiona, Bohnet, Sabine, Boleti, Ekaterini, Borghaei, Hossein, Bradbury, Penelope, Brighenti, Matteo, Campbell, Nicholas, Campbell, Toby, Canon, Jean-Luc, Cappuzzo, Federico, Costa, Enric Carcereny, Cavanna, Luigi, Cetnar, Jeremy, Chella, Antonio, Chouaid, Christos, Christoph, Daniel, Castán, Javier Cortés, Dakhil, Shaker, de Castro Carpeño, Francisco Javier, de Marinis, Filippo, Delmonte, Angelo, Demedts, Ingel, Demey, Wim, Dits, Joyce, del Pilar Diz Taín, Maria, Gómez, Manuel Dómine, Dorius, Timothy, Dumoulin, Daphne, Duruisseaux, Michaël, Eaton, Keith, González, Emilio Esteban, Evans, Devon, Faehling, Martin, Farrell, Nicholas, Feinstein, Trevor, Font, Enriqueta Felip, Garcia Campelo, Maria Rosario, Garon, Edward, Garrido López, María Pilar, Germonpré, Paul, Gersten, Todd, Cao, Maria Gonzalez, Gopaluni, Srivalli, Greillier, Laurent, Grossi, Francesco, Guisier, Florian, Gurubhagavatula, Sarada, Calderón, Vanesa Gutiérrez, Hakimian, David, Hall, Richard, Jr., Hao, Desirée, Harris, Ronald, Hashemi, Sayed, He, Kai, Hendriks, Lizza, Huang, Chao, Ibrahim, Emad, Jain, Sharad, Johnson, Melissa, Jones, Benjamin, Jones, Monte, Juan Vidal, Óscar José, Juergens, Rosalyn, Kaderbhai, Courèche, Kastelijn, Elisabeth A (Lisanne), Keresztes, Roger, Kio, Ebenezer, Kokowski, Konrad, Konduri, Kartik, Kulkarni, Swati, Kuon, Jonas, Kurkjian, Carla, Labbé, Catherine, Lerner, Rachel, Lim, Farah, Madroszyk-Flandin, Anne, Marathe, Omkar, Martincic, Danko, McClay, Edward, McIntyre, Kristi, Mekhail, Tarek, Misino, Andrea, Molinier, Olivier, Morabito, Alessandro, Morócz, Éva, Müller, Veronika, Nagy, Tünde, Nguyen, Anthony V., Nidhiry, Emmanuel, Okazaki, Ian, Ortega-Granados, Ana Laura, Ostoros, Gyula, Oubre, David, Owen, Scott, Pachipala, Krishna, Park, David, Patel, Pareshkumar, Percent, Ivor, Pérol, Maurice, Peters, Solange, Piet, Berber, Planchard, David, Polychronis, Andreas, Aix, Santiago Ponce, Pons-Tostivint, Elvire, Popat, Sanjaykumar, Pulla, Mariano Provencio, Quantin, Xavier, Quéré, Gilles, Rafique, Noman, Ramaekers, Ryan, Reck, Martin, Reiman, Anthony, Reinmuth, Niels, Reynolds, Craig, Rodríguez-Abreu, Delvys, Romano, Gianpiero, Roque, Tammy, Salzberg, Matthew, Sanborn, Rachel, Sandiego, Sergio, Schaefer, Eric, Schreeder, Marshall, Seetharamu, Nagashree, Seneviratne, Lasika, Shah, Purvi, Shunyakov, Leonid, Slater, Dennis, Parra, Hector Soto, Stigt, Johannes, Stilwill, Joseph, Su, Jingdong, Surmont, Veerle, Swink, Alicia, Szalai, Zsuzsanna, Talbot, Toby, Garcia, Alvaro Taus, Theelen, Willemijn, Thompson, Jonathan, Tiseo, Marcello, Uprety, Dipesh, Uyeki, James, van der Leest, Kornelius Cor, Van Ho, Anthony, van Putten, John, Estévez, Sergio Vázquez, Veatch, Andrea, Vergnenègre, Alain, Ward, Patrick, Weise, Amy, Weiss, Matthias, Whitehurst, Matthew, Zai, Silvia, Zalcman, Gérard, Zuniga, Richard, Borghaei, H., de Marinis, F., Dumoulin, D., Reynolds, C., Theelen, W.S.M.E., Percent, I., Gutierrez Calderon, V., Johnson, M.L., Madroszyk-Flandin, A., Garon, E.B., He, K., Planchard, D., Reck, M., Popat, S., Herbst, R.S., Leal, T.A., Shazer, R.L., Yan, X., Harrigan, R., and Peters, S.

Published
2024
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10. Characterization of KRAS Mutation Subtypes in Non-small Cell Lung Cancer.

Author

Judd, Julia, Abdel Karim, Nagla, Khan, Hina, Naqash, Abdul, Baca, Yasmine, Xiu, Joanne, VanderWalde, Ari, Mamdani, Hirva, Raez, Luis, Nagasaka, Misako, Pai, Sachin, Socinski, Mark, Nieva, Jorge, Kim, Chul, Wozniak, Antoinette, Ikpeazu, Chukwuemeka, de Lima Lopes, Gilberto, Spira, Alexander, Korn, W, Kim, Edward, Liu, Stephen, and Borghaei, Hossein

Subjects
Carcinoma, Non-Small-Cell Lung, High-Throughput Nucleotide Sequencing, Humans, Lung Neoplasms, Microsatellite Instability, Mutation, Prognosis, Proto-Oncogene Proteins p21(ras)
Abstract

KRAS is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different KRAS mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, KRAS-mutated non-small cell lung cancer (NSCLC) in a large national cohort to help guide future therapeutic development.Molecular profiles of 17,095 NSCLC specimens were obtained using DNA next-generation sequencing of 592 genes (Caris Life Sciences) and classified on the basis of presence and subtype of KRAS mutations. Co-occurring genomic alterations, tumor mutational burden (TMB), and PD-L1 expression [22C3, tumor proportion score (TPS) score] were analyzed by KRAS mutation type.Across the cohort, 4,706 (27.5%) samples harbored a KRAS mutation. The most common subtype was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of KRAS mutations was 37.2% among adenocarcinomas and 4.4% in squamous cell carcinomas. Rates of high TMB (≥10 mutations/Mb) and PD-L1 expression varied across KRAS mutation subtypes. KRAS G12C was the most likely to be PD-L1 positive (65.5% TPS ≥ 1%) and PD-L1 high (41.3% TPS ≥ 50%). STK11 was mutated in 8.6% of KRAS wild-type NSCLC but more frequent in KRAS-mutant NSCLC, with the highest rate in G13 (36.2%). TP53 mutations were more frequent in KRAS wild-type NSCLC (73.6%).KRAS mutation subtypes have different co-occurring mutations and a distinct genomic landscape. The clinical relevance of these differences in the context of specific therapeutic interventions warrants investigation.

Published
2021

11. Impact of XPO1 mutations on survival outcomes in metastatic non-small cell lung cancer (NSCLC).

Author

Nagasaka, Misako, Asad, Mohammad, Al Hallak, Mohammed, Uddin, Md, Sukari, Ammar, Baca, Yasmine, Xiu, Joanne, Magee, Dan, Mamdani, Hirva, Uprety, Dipesh, Kim, Chul, Xia, Bing, Liu, Stephen, Nieva, Jorge, Lopes, Gilberto, Bepler, Gerold, Borghaei, Hossein, Demeure, Michael, Raez, Luis, Ma, Patrick, Puri, Sonam, Korn, W, and Azmi, Asfar

Subjects
NGS, NSCLC, Nuclear Protein Transport, Tumor Mutational Burden, XPO1, Carcinoma, Non-Small-Cell Lung, Humans, Karyopherins, Lung Neoplasms, Mutation, Receptors, Cytoplasmic and Nuclear
Abstract

BACKGROUND: Nuclear protein transport is essential in guiding the traffic of important proteins and RNAs between the nucleus and cytoplasm. Export of proteins from the nucleus is mostly regulated by Exportin 1 (XPO1). In cancer, XPO1 is almost universally hyperactive and can promote the export of important tumor suppressors to the cytoplasm. Currently, there are no studies evaluating XPO1 amplifications and mutations in NSCLC and the impact on outcomes. METHODS: Tumor samples were analyzed using next-generation sequencing (NGS) (NextSeq, 592 Genes), immunohistochemistry (IHC), and whole transcriptome sequencing (WTS, NovaSeq) (Caris Life Sciences, Phoenix, AZ). Survival was extracted from insurance claims data and calculated from time of tissue collection to last contact using Kaplan-Meier estimate. RESULTS: Among 18,218 NSCLC tumors sequenced, 26 harbored XPO1 mutations and 24 had amplifications. XPO1 mutant tumors were more likely to have high TMB (79% vs. 52%, p = 0.007) and less likely to have high PD-L1 (32% vs. 68%, p = 0.03). KRAS co-mutations were seen in 19% (n = 5) and EGFR co-mutations were rare (n = 2). Among the 17,449 NSCLC tumors with clinical data, there were 24 XPO1 mutant. Comparison of survival between XPO1 mutant and WT showed a negative association with a hazard ratio (HR) of 1.932 (95% CI: 1.144-3.264 p = 0.012). XPO1 amplification was not associated with survival. CONCLUSIONS: XPO1 pathogenic mutations were associated with a poor survival in NSCLC. Although XPO1 mutations are rare in NSCLC, further studies to assess its associations with treatment responses are warranted.

Published
2021

14. Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1

Author

Reck, Martin, Ciuleanu, Tudor-Eliade, Lee, Jong-Seok, Schenker, Michael, Zurawski, Bogdan, Kim, Sang-We, Mahave, Mauricio, Alexandru, Aurelia, Peters, Solange, Pluzanski, Adam, Caro, Reyes Bernabe, Linardou, Helena, Burgers, Jacobus A., Nishio, Makoto, Martinez-Marti, Alex, Azuma, Koichi, Axelrod, Rita, Paz-Ares, Luis G., Ramalingam, Suresh S., Borghaei, Hossein, O’Byrne, Kenneth J., Li, Li, Bushong, Judith, Gupta, Ravi G., Grootendorst, Diederik J., Eccles, Laura J., and Brahmer, Julie R.

Published
2023
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15. Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817

Author

Paz-Ares, Luis G., Ciuleanu, Tudor-Eliade, Pluzanski, Adam, Lee, Jong-Seok, Gainor, Justin F., Otterson, Gregory A., Audigier-Valette, Clarisse, Ready, Neal, Schenker, Michael, Linardou, Helena, Caro, Reyes Bernabe, Provencio, Mariano, Zurawski, Bogdan, Lee, Ki Hyeong, Kim, Sang-We, Caserta, Claudia, Ramalingam, Suresh S., Spigel, David R., Brahmer, Julie R., Reck, Martin, O’Byrne, Kenneth J., Girard, Nicolas, Popat, Sanjay, Peters, Solange, Memaj, Arteid, Nathan, Faith, Aanur, Nivedita, and Borghaei, Hossein

Published
2023
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16. Sotorasib versus pembrolizumab in combination with platinum doublet chemotherapy as first-line treatment for metastatic or locally advanced, PD-L1 negative, KRAS G12C-mutated NSCLC (CodeBreaK 202).

Author

Barlesi, Fabrice, primary, Felip, Enriqueta, additional, Popat, Sanjay, additional, Solomon, Benjamin J., additional, Wolf, Juergen, additional, Li, Bob T., additional, Wu, Yi-Long, additional, Kerr, Keith, additional, Akamatsu, Hiroaki, additional, Camidge, David Ross, additional, Gupta, Ravi G., additional, Meloni, Alison, additional, Dai, Tian, additional, and Borghaei, Hossein, additional

Published
2024
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17. TRITON: Phase 3b study of tremelimumab (T) + durvalumab (D) vs pembrolizumab (P), in combination with chemotherapy (CT), in non-squamous (NSQ) metastatic NSCLC (mNSCLC) with STK11and/or KEAP1 and/or KRAS mutations.

Author

Skoulidis, Ferdinandos, primary, Borghaei, Hossein, additional, Garon, Edward B., additional, Leal, Ticiana, additional, Liu, Stephen V., additional, Nadler, Eric S., additional, Patel, Sandip Pravin, additional, Velcheti, Vamsidhar, additional, Gautam, Ashish, additional, Emeribe, Ugochinyere, additional, Luciani-Silverman, Luisa, additional, and Heymach, John, additional

Published
2024
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28. A process to reanalyze clinical DNA sequencing data for biomarker matching in the Lung-MAP Master Protocol

Author

Neal, Joel W, primary, Minichiello, Katherine, additional, Brennick, Ryan, additional, Huang, Richard S P, additional, Hiemenz, Matthew C, additional, Amler, Cornel, additional, Patel, Jyoti, additional, Herbst, Roy, additional, Reckamp, Karen L, additional, Borghaei, Hossein, additional, Highleyman, Louise, additional, Redman, Mary W, additional, Pasquina, Lincoln W, additional, and Kozono, David E, additional

Published
2024
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29. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial

Author

Paz-Ares, Luis G., Ramalingam, Suresh S., Ciuleanu, Tudor-Eliade, Lee, Jong-Seok, Urban, Laszlo, Caro, Reyes Bernabe, Park, Keunchil, Sakai, Hiroshi, Ohe, Yuichiro, Nishio, Makoto, Audigier-Valette, Clarisse, Burgers, Jacobus A., Pluzanski, Adam, Sangha, Randeep, Gallardo, Carlos, Takeda, Masayuki, Linardou, Helena, Lupinacci, Lorena, Lee, Ki Hyeong, Caserta, Claudia, Provencio, Mariano, Carcereny, Enric, Otterson, Gregory A., Schenker, Michael, Zurawski, Bogdan, Alexandru, Aurelia, Vergnenegre, Alain, Raimbourg, Judith, Feeney, Kynan, Kim, Sang-We, Borghaei, Hossein, O'Byrne, Kenneth John, Hellmann, Matthew D., Memaj, Arteid, Nathan, Faith Ellen, Bushong, Judith, Tran, Phuong, Brahmer, Julie R., and Reck, Martin

Published
2022
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30. The Effects of HER2 Alterations in EGFR Mutant Non-small Cell Lung Cancer

Author

Nagasaka, Misako, Singh, Vijendra, Baca, Yasmine, Sukari, Ammar, Kim, Chul, Mamdani, Hirva, Spira, Alexander I., Uprety, Dipesh, Bepler, Gerold, Kim, Edward S., Raez, Luis E., Pai, Sachin Gopalkrishna, Ikpeazu, Chukwuemeka, Oberley, Matthew, Feldman, Rebecca, Xiu, Joanne, Korn, W. Michael, Wozniak, Antoinette J., Borghaei, Hossein, and Liu, Stephen V.

Published
2022
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31. Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial

Author

Forde, Patrick M., Anagnostou, Valsamo, Sun, Zhuoxin, Dahlberg, Suzanne E., Kindler, Hedy L., Niknafs, Noushin, Purcell, Thomas, Santana-Davila, Rafael, Dudek, Arkadiusz Z., Borghaei, Hossein, Lanis, Mara, Belcaid, Zineb, Smith, Kellie N., Balan, Archana, White, James R., Cherry, Christopher, Ashok Sivakumar, I. K., Shao, Xiaoshan M., Chan, Hok Yee, Singh, Dipika, Thapa, Sampriti, Illei, Peter B., Pardoll, Drew M., Karchin, Rachel, Velculescu, Victor E., Brahmer, Julie R., and Ramalingam, Suresh S.

Published
2021
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32. Incidence, Correlates, and Prognostic Significance of Mixed Response in Advanced Non-small Cell Lung Cancer.

Author

Gerber, David E, Wang, Yating, Ramalingam, Suresh S, Bhalla, Sheena, Sun, Zhuoxin, Borghaei, Hossein, Brahmer, Julie R, and Schiller, Joan H

Subjects
THERAPEUTIC use of antineoplastic agents, PEARSON correlation (Statistics), RISK assessment, BEVACIZUMAB, TREATMENT effectiveness, CARBOPLATIN, MANN Whitney U Test, CHI-squared test, MULTIVARIATE analysis, LOG-rank test, CANCER chemotherapy, CANCER cells, LUNG cancer, TUMOR classification, PACLITAXEL, CONFIDENCE intervals, SURVIVAL analysis (Biometry), OVERALL survival, PROPORTIONAL hazards models
Abstract

Background Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non–small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy. Patients and Methods We analyzed patient-level data from ECOG-ACRIN E5508 (carboplatin-paclitaxel + bevacizumab induction followed by randomization to maintenance therapy regimens). For patients with at least 2 target lesions and available measurements after cycle 2, we characterized response as homogeneous response (HR, similar behavior of all lesions), MR (similar behavior but >30% difference in magnitude of best and least responding lesions), or true mixed response (TMR, best and least responding lesions showing different behavior: ≥10% growth versus ≥10% shrinkage). We compared category characteristics using Mann-Whitney U and Chi-square tests, and overall survival (OS) using log-rank test and Cox models. Results Among 965 evaluable patients, HR occurred in 609 patients (63%), MR in 208 (22%), and TMR in 148 (15%). Median OS was 13.6 months for HR, 12.0 months for MR, and 7.6 months for TMR (P  < .001). Compared to HR, TMR had inferior OS among stable disease cases (HR 1.62; 95% CI, 1.23-2.12; P  < .001) and a trend toward inferior OS among progressive disease cases (HR 1.39; 95% CI, 0.83-2.33; P  = .2). In multivariate analysis, TMR was associated with worse OS (HR 1.48; 95% CI, 1.22-1.79; P  < .001). Conclusion True mixed response occurs in a substantial minority of lung cancer cases treated with chemotherapy and independently confers poor prognosis. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer

Author

Ahn, Myung-Ju, primary, Cho, Byoung Chul, additional, Felip, Enriqueta, additional, Korantzis, Ippokratis, additional, Ohashi, Kadoaki, additional, Majem, Margarita, additional, Juan-Vidal, Oscar, additional, Handzhiev, Sabin, additional, Izumi, Hiroki, additional, Lee, Jong-Seok, additional, Dziadziuszko, Rafal, additional, Wolf, Jürgen, additional, Blackhall, Fiona, additional, Reck, Martin, additional, Bustamante Alvarez, Jean, additional, Hummel, Horst-Dieter, additional, Dingemans, Anne-Marie C., additional, Sands, Jacob, additional, Akamatsu, Hiroaki, additional, Owonikoko, Taofeek K., additional, Ramalingam, Suresh S., additional, Borghaei, Hossein, additional, Johnson, Melissa L., additional, Huang, Shuang, additional, Mukherjee, Sujoy, additional, Minocha, Mukul, additional, Jiang, Tony, additional, Martinez, Pablo, additional, Anderson, Erik S., additional, and Paz-Ares, Luis, additional

Published
2023
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34. Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non–Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked

Author

Bodor, J. Nicholas, primary, Patel, Jyoti D., additional, Wakelee, Heather A., additional, Levy, Benjamin P., additional, Borghaei, Hossein, additional, Pellini, Bruna, additional, Costello, Michael R., additional, Dowell, Jonathan E., additional, Finley, Gene, additional, Huang, Chao H., additional, Neal, Joel W., additional, Nieva, Jorge J, additional, Puri, Sonam, additional, Socinski, Mark A., additional, Thomas, Christian, additional, Ross, Eric A., additional, Litwin, Samuel, additional, Clapper, Margie L., additional, and Treat, Joseph, additional

Published
2023
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35. Validation of a Molecular Diagnostic Test for Circulating Tumor DNA by Next-Gen Sequencing

Author

Fernandez, Sandra V., primary, Tan, Yin Fei, additional, Rao, Shilpa, additional, Fittipaldi, Patricia, additional, Sheriff, Fathima, additional, Borghaei, Hossein, additional, Dotan, Efrat, additional, Winn, Jennifer S., additional, Edelman, Martin J., additional, Treat, Joseph, additional, Judd, Julia, additional, Alpaugh, R. Katherine, additional, Wang, Y. Lynn, additional, Yu, Jian Q., additional, Wasik, Mariusz, additional, and Baldwin, Don A., additional

Published
2023
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36. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

Author

Borghaei, H., primary, de Marinis, F., additional, Dumoulin, D., additional, Reynolds, C., additional, Theelen, W.S.M.E., additional, Percent, I., additional, Gutierrez Calderon, V., additional, Johnson, M.L., additional, Madroszyk-Flandin, A., additional, Garon, E.B., additional, He, K., additional, Planchard, D., additional, Reck, M., additional, Popat, S., additional, Herbst, R.S., additional, Leal, T.A., additional, Shazer, R.L., additional, Yan, X., additional, Harrigan, R., additional, Peters, S., additional, Abdel-Karim, Isam, additional, Abdelsalam, Mahmoud, additional, Addeo, Alfredo, additional, Aguado, Carlos, additional, Alexander, Patrick, additional, Alt, Jürgen, additional, Azzi, Georges, additional, Balaraman, Rama, additional, Biesma, Bonne, additional, Blackhall, Fiona, additional, Bohnet, Sabine, additional, Boleti, Ekaterini, additional, Borghaei, Hossein, additional, Bradbury, Penelope, additional, Brighenti, Matteo, additional, Campbell, Nicholas, additional, Campbell, Toby, additional, Canon, Jean-Luc, additional, Cappuzzo, Federico, additional, Costa, Enric Carcereny, additional, Cavanna, Luigi, additional, Cetnar, Jeremy, additional, Chella, Antonio, additional, Chouaid, Christos, additional, Christoph, Daniel, additional, Castán, Javier Cortés, additional, Dakhil, Shaker, additional, de Castro Carpeño, Francisco Javier, additional, de Marinis, Filippo, additional, Delmonte, Angelo, additional, Demedts, Ingel, additional, Demey, Wim, additional, Dits, Joyce, additional, del Pilar Diz Taín, Maria, additional, Gómez, Manuel Dómine, additional, Dorius, Timothy, additional, Dumoulin, Daphne, additional, Duruisseaux, Michaël, additional, Eaton, Keith, additional, González, Emilio Esteban, additional, Evans, Devon, additional, Faehling, Martin, additional, Farrell, Nicholas, additional, Feinstein, Trevor, additional, Font, Enriqueta Felip, additional, Garcia Campelo, Maria Rosario, additional, Garon, Edward, additional, Garrido López, María Pilar, additional, Germonpré, Paul, additional, Gersten, Todd, additional, Cao, Maria Gonzalez, additional, Gopaluni, Srivalli, additional, Greillier, Laurent, additional, Grossi, Francesco, additional, Guisier, Florian, additional, Gurubhagavatula, Sarada, additional, Calderón, Vanesa Gutiérrez, additional, Hakimian, David, additional, Hall, Richard, additional, Hao, Desirée, additional, Harris, Ronald, additional, Hashemi, Sayed, additional, He, Kai, additional, Hendriks, Lizza, additional, Huang, Chao, additional, Ibrahim, Emad, additional, Jain, Sharad, additional, Johnson, Melissa, additional, Jones, Benjamin, additional, Jones, Monte, additional, Juan Vidal, Óscar José, additional, Juergens, Rosalyn, additional, Kaderbhai, Courèche, additional, Kastelijn, Elisabeth A (Lisanne), additional, Keresztes, Roger, additional, Kio, Ebenezer, additional, Kokowski, Konrad, additional, Konduri, Kartik, additional, Kulkarni, Swati, additional, Kuon, Jonas, additional, Kurkjian, Carla, additional, Labbé, Catherine, additional, Lerner, Rachel, additional, Lim, Farah, additional, Madroszyk-Flandin, Anne, additional, Marathe, Omkar, additional, Martincic, Danko, additional, McClay, Edward, additional, McIntyre, Kristi, additional, Mekhail, Tarek, additional, Misino, Andrea, additional, Molinier, Olivier, additional, Morabito, Alessandro, additional, Morócz, Éva, additional, Müller, Veronika, additional, Nagy, Tünde, additional, Nguyen, Anthony V., additional, Nidhiry, Emmanuel, additional, Okazaki, Ian, additional, Ortega-Granados, Ana Laura, additional, Ostoros, Gyula, additional, Oubre, David, additional, Owen, Scott, additional, Pachipala, Krishna, additional, Park, David, additional, Patel, Pareshkumar, additional, Percent, Ivor, additional, Pérol, Maurice, additional, Peters, Solange, additional, Piet, Berber, additional, Planchard, David, additional, Polychronis, Andreas, additional, Aix, Santiago Ponce, additional, Pons-Tostivint, Elvire, additional, Popat, Sanjaykumar, additional, Pulla, Mariano Provencio, additional, Quantin, Xavier, additional, Quéré, Gilles, additional, Rafique, Noman, additional, Ramaekers, Ryan, additional, Reck, Martin, additional, Reiman, Anthony, additional, Reinmuth, Niels, additional, Reynolds, Craig, additional, Rodríguez-Abreu, Delvys, additional, Romano, Gianpiero, additional, Roque, Tammy, additional, Salzberg, Matthew, additional, Sanborn, Rachel, additional, Sandiego, Sergio, additional, Schaefer, Eric, additional, Schreeder, Marshall, additional, Seetharamu, Nagashree, additional, Seneviratne, Lasika, additional, Shah, Purvi, additional, Shunyakov, Leonid, additional, Slater, Dennis, additional, Parra, Hector Soto, additional, Stigt, Johannes, additional, Stilwill, Joseph, additional, Su, Jingdong, additional, Surmont, Veerle, additional, Swink, Alicia, additional, Szalai, Zsuzsanna, additional, Talbot, Toby, additional, Garcia, Alvaro Taus, additional, Theelen, Willemijn, additional, Thompson, Jonathan, additional, Tiseo, Marcello, additional, Uprety, Dipesh, additional, Uyeki, James, additional, van der Leest, Kornelius Cor, additional, Van Ho, Anthony, additional, van Putten, John, additional, Estévez, Sergio Vázquez, additional, Veatch, Andrea, additional, Vergnenègre, Alain, additional, Ward, Patrick, additional, Weise, Amy, additional, Weiss, Matthias, additional, Whitehurst, Matthew, additional, Zai, Silvia, additional, Zalcman, Gérard, additional, and Zuniga, Richard, additional

Published
2023
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37. Influence of TP53 Comutation on the Tumor Immune Microenvironment and Clinical Outcomes With Immune Checkpoint Inhibitors in STK11 -Mutant Non–Small-Cell Lung Cancer.

Author

Naqash, Abdul Rafeh, Floudas, Charalampos S., Aber, Etan, Maoz, Asaf, Nassar, Amin H., Adib, Elio, Choucair, Khalil, Xiu, Joanne, Baca, Yasmine, Ricciuti, Biagio, Alessi, Joao V., Awad, Mark M., Kim, Chul, Judd, Julia, Raez, Luis E., Lopes, Gilberto, Nieva, Jorge J., Borghaei, Hossein, Takebe, Naoko, and Ma, Patrick C.

Subjects
IMMUNE checkpoint inhibitors, NON-small-cell lung carcinoma, GLUTAMINE, TUMOR microenvironment, GLUTAMINE synthetase, KILLER cells, METABOLIC reprogramming
Abstract

PURPOSE: Non–small-cell lung cancer (NSCLC) with STK11 mut has inferior outcomes to immune checkpoint inhibitors (ICIs). Using multiomics, we evaluated whether a subtype of STK11 mut NSCLC with a uniquely inflamed tumor immune microenvironment (TIME) harboring TP53 comutations could have favorable outcomes to ICIs. PATIENTS AND METHODS: NSCLC tumors (N = 16,896) were analyzed by next-generation sequencing (DNA-Seq/592 genes). A subset (n = 5,034) underwent gene expression profiling (RNA-Seq/whole transcriptome). Exome-level neoantigen load for STK11 mut NSCLC was obtained from published pan-immune analysis. Tumor immune cell content was obtained from transcriptome profiles using the microenvironment cell population (MCP) counter. ICI data from POPLAR/OAK (n = 34) and the study by Rizvi et al (n = 49) were used to model progression-free survival (PFS), and a separate ICI-treated cohort (n = 53) from Dana-Farber Cancer Institute (DFCI) was used to assess time to treatment failure (TTF) and tumor RECIST response for STK11 mut TP53 mut versus STK11 mut TP53 wt NSCLC. RESULTS: Overall, 12.6% of NSCLC tumors had a STK11 mut with the proportions of tumor mutational burden (TMB)-high (≥10 mut/Mb), PD-L1 ≥50%, and microsatellite instability-high being 38.3%, 11.8%, and 0.72%, respectively. Unsupervised hierarchical clustering of STK11 mut (n = 463) for stimulator of interferon-gamma (STING) pathway genes identified a STING-high cluster, which was significantly enriched in TP53 mut NSCLC (P <.01). Compared with STK11 mut TP53 wt, tumors with STK11 mut TP53 mut had higher CD8+T cells and natural killer cells (P <.01), higher TMB (P <.001) and neoantigen load (P <.001), and increased expression of MYC and HIF-1A (P <.01), along with higher expression (P <.01) of glycolysis/glutamine metabolism genes. Meta-analysis of data from OAK/POPLAR and the study by Rizvi et al showed a trend toward improved PFS in patients with STK11 mut TP53 mut. In the DFCI cohort, compared with the STK11 mut TP53 wt cohort, the STK11 mut TP53 mut tumors had higher objective response rates (42.9% v 16.7%; P =.04) and also had longer TTF (14.5 v 4.5 months, P adj =.054) with ICI. CONCLUSION: STK11 mut NSCLC with TP53 comutation is a distinct subgroup with an immunologically active TIME and metabolic reprogramming. These properties should be exploited to guide patient selection for novel ICI-based combination approaches. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Impact of gender and mutational differences in hormone receptor expressing non-small cell lung cancer

Author

Hsu, Robert, primary, Chen, Denaly, additional, Xia, Bing, additional, Feldman, Rebecca, additional, Cozen, Wendy, additional, Raez, Luis E., additional, Borghaei, Hossein, additional, Kim, Chul, additional, Nagasaka, Misako, additional, Mamdani, Hirva, additional, Vanderwalde, Ari M., additional, Lopes, Gilberto, additional, Socinski, Mark A., additional, Wozniak, Antoinette J., additional, Spira, Alexander I., additional, Liu, Stephen V., additional, and Nieva, Jorge J., additional

Published
2023
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39. Systemic and intracranial outcomes with first-line nivolumab plus ipilimumab in patients with metastatic non–small cell lung cancer and baseline brain metastases from CheckMate 227 Part 1

Author

Reck, Martin, primary, Ciuleanu, Tudor-Eliade, additional, Lee, Jong-Seok, additional, Schenker, Michael, additional, Zurawski, Bogdan, additional, Kim, Sang-We, additional, Mahave, Mauricio, additional, Alexandru, Aurelia, additional, Peters, Solange, additional, Pluzanski, Adam, additional, Caro, Reyes Bernabe, additional, Linardou, Helena, additional, Burgers, Jacobus A., additional, Nishio, Makoto, additional, Martinez-Marti, Alex, additional, Azuma, Koichi, additional, Axelrod, Rita, additional, Paz-Ares, Luis G., additional, Ramalingam, Suresh S., additional, Borghaei, Hossein, additional, O’Byrne, Kenneth J., additional, Li, Li, additional, Bushong, Judith, additional, Gupta, Ravi G., additional, Grootendorst, Diederik J., additional, Eccles, Laura J., additional, and Brahmer, Julie R., additional

Published
2023
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40. ERBB family fusions are recurrent and actionable oncogenic targets across cancer types

Author

Schubert, Laura, primary, Elliott, Andrew, additional, Le, Anh T., additional, Estrada-Bernal, Adriana, additional, Doebele, Robert C., additional, Lou, Emil, additional, Borghaei, Hossein, additional, Demeure, Michael J., additional, Kurzrock, Razelle, additional, Reuss, Joshua E., additional, Ou, Sai-Hong Ignatius, additional, Braxton, David R., additional, Thomas, Christian A., additional, Darabi, Sourat, additional, Korn, Wolfgang Michael, additional, El-Deiry, Wafik S., additional, and Liu, Stephen V., additional

Published
2023
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41. Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817

Author

Bristol Myers Squibb Foundation, Paz-Ares, Luis, Ciuleanu, Tudor-Eliade, Pluzanski, Adam, Lee, Jong-Seok, Gainor, Justin F., Otterson, Gregory A., Audigier-Valette, Clarisse, Ready, Neal, Schenker, Michael, Linardou, Helena, Caro, Reyes Bernabe, Provencio, Mariano, Zurawski, Bogdan, Lee, Ki Hyeong, Kim, Sang-We, Caserta, Claudia, Ramalingam, Suresh S., Spigel, David R., Brahmer, Julie R., Reck, Martin, O'Byrne, Kenneth J., Girard, Nicolas, Popat, Sanjay, Peters, Solange, Memaj, Arteid, Nathan, Faith Ellen, Aanur, Nivedita, Borghaei, Hossein, Bristol Myers Squibb Foundation, Paz-Ares, Luis, Ciuleanu, Tudor-Eliade, Pluzanski, Adam, Lee, Jong-Seok, Gainor, Justin F., Otterson, Gregory A., Audigier-Valette, Clarisse, Ready, Neal, Schenker, Michael, Linardou, Helena, Caro, Reyes Bernabe, Provencio, Mariano, Zurawski, Bogdan, Lee, Ki Hyeong, Kim, Sang-We, Caserta, Claudia, Ramalingam, Suresh S., Spigel, David R., Brahmer, Julie R., Reck, Martin, O'Byrne, Kenneth J., Girard, Nicolas, Popat, Sanjay, Peters, Solange, Memaj, Arteid, Nathan, Faith Ellen, Aanur, Nivedita, and Borghaei, Hossein

Abstract

[Introduction] We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs)., [Methods] We pooled data from three first-line NIVO+IPI studies (NIVO, 3 mg/kg or 240 mg every 2 wk; IPI, 1 mg/kg every 6 wk) in metastatic NSCLC (CheckMate 227 part 1, CheckMate 817 cohort A, CheckMate 568 part 1). Safety end points included TRAEs and immune-mediated adverse events (IMAEs) in the pooled population and patients aged 75 years or older., [Results] In the pooled population (N = 1255), any-grade TRAEs occurred in 78% of the patients, grade 3 or 4 TRAEs in 34%, and discontinuation of any regimen component owing to TRAEs in 21%. The most frequent TRAE and IMAE were diarrhea (20%; grade 3 or 4, 2%) and rash (17%; grade 3 or 4, 3%), respectively. The most common grade 3 or 4 IMAEs were hepatitis (5%) and diarrhea/colitis and pneumonitis (4% each). Pneumonitis was the most common cause of treatment-related death (5 of 16). Safety in patients aged 75 years or older (n = 174) was generally similar to the overall population, but discontinuation of any regimen component owing to TRAEs was more common (29%). In patients discontinuing NIVO+IPI owing to TRAEs (n = 225), 3-year overall survival was 50% (95% confidence interval: 42.6–56.0), and 42% (31.2–52.4) of 130 responders remained in response 2 years after discontinuation., [Conclusions] First-line NIVO+IPI was well tolerated in this large population with metastatic NSCLC and in patients aged 75 years or older. Discontinuation owing to TRAEs did not reduce long-term survival.

Published
2023

42. Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227

Author

Brahmer, Julie R., Lee, Jong-Seok, Ciuleanu, Tudor-Eliade, Bernabé Caro, Reyes, Nishio, Makoto, Urban, Laszlo, Audigier-Valette, Clarisse, Lupinacci, Lorena, Sangha, Randeep, Pluzanski, Adam, Burgers, Jacobus, Mahave, Mauricio, Ahmed, Samreen, Schoenfeld, Adam J., Paz-Ares, Luis, Reck, Martin, Borghaei, Hossein, O'Byrne, Kenneth J., Gupta, Ravi G., Bushong, Judith, Li, Li, Blum, Steven I., Eccles, Laura J., Ramalingam, Suresh S., Brahmer, Julie R., Lee, Jong-Seok, Ciuleanu, Tudor-Eliade, Bernabé Caro, Reyes, Nishio, Makoto, Urban, Laszlo, Audigier-Valette, Clarisse, Lupinacci, Lorena, Sangha, Randeep, Pluzanski, Adam, Burgers, Jacobus, Mahave, Mauricio, Ahmed, Samreen, Schoenfeld, Adam J., Paz-Ares, Luis, Reck, Martin, Borghaei, Hossein, O'Byrne, Kenneth J., Gupta, Ravi G., Bushong, Judith, Li, Li, Blum, Steven I., Eccles, Laura J., and Ramalingam, Suresh S.

Abstract

[Purpose] We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non–small-cell lung cancer, regardless of tumor programmed death ligand 1 (PD-L1) status., [Methods] Adults with stage IV/recurrent non–small-cell lung cancer without EGFR mutations or ALK alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life., [Results] At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed., [Conclusion] With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non–small-cell lung cancer.

Published
2023

43. Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1

Author

Bristol Myers Squibb Foundation, Reck, Martin, Ciuleanu, Tudor-Eliade, Lee, Jong-Seok, Schenker, Michael, Zurawski, Bogdan, Kim, Sang-We, Mahave, Mauricio, Alexandru, Aurelia, Peters, Solange, Pluzanski, Adam, Bernabé Caro, Reyes, Linardou, Helena, Burgers, Jacobus A., Nishio, Makoto, Martinez-Marti, Alex, Azuma, Koichi, Axelrod, Rita, Paz-Ares, Luis, Ramalingam, Suresh S., Borghaei, Hossein, O'Byrne, Kenneth J., Li, Li, Bushong, Judith, Gupta, Ravi G., Grootendorst, Diederik J., Eccles, Laura J., Brahmer, Julie R., Bristol Myers Squibb Foundation, Reck, Martin, Ciuleanu, Tudor-Eliade, Lee, Jong-Seok, Schenker, Michael, Zurawski, Bogdan, Kim, Sang-We, Mahave, Mauricio, Alexandru, Aurelia, Peters, Solange, Pluzanski, Adam, Bernabé Caro, Reyes, Linardou, Helena, Burgers, Jacobus A., Nishio, Makoto, Martinez-Marti, Alex, Azuma, Koichi, Axelrod, Rita, Paz-Ares, Luis, Ramalingam, Suresh S., Borghaei, Hossein, O'Byrne, Kenneth J., Li, Li, Bushong, Judith, Gupta, Ravi G., Grootendorst, Diederik J., Eccles, Laura J., and Brahmer, Julie R.

Abstract

[Introduction] In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic and intracranial efficacy outcomes and safety by baseline brain metastasis status at 5 years’ minimum follow-up., [Methods] Treatment-naive adults with stage IV or recurrent NSCLC without EGFR or ALK alterations, including asymptomatic patients with treated brain metastases, were enrolled. Patients with tumor PD-L1 greater than or equal to 1% were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy; patients with tumor PD-L1 less than 1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy groups. Assessments included OS, systemic and intracranial progression-free survival per blinded independent central review, new brain lesion development, and safety. Brain imaging was performed at baseline (all randomized patients) and approximately every 12 weeks thereafter (patients with baseline brain metastases only)., [Results] Overall, 202 of 1739 randomized patients had baseline brain metastases (nivolumab plus ipilimumab: 68; chemotherapy: 66). At 61.3 months’ minimum follow-up, nivolumab plus ipilimumab prolonged OS versus chemotherapy in patients with baseline brain metastases (hazard ratio = 0.63; 95% confidence interval: 0.43–0.92) and in those without (hazard ratio = 0.76; 95% confidence interval: 0.66–0.87). In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ipilimumab (12% and 16%, respectively) than chemotherapy (0% and 6%). Fewer patients with baseline brain metastases developed new brain lesions with nivolumab plus ipilimumab (4%) versus chemotherapy (20%). No new safety signals were observed., [Conclusions] With all patients off immunotherapy for more than or equal to 3 years, nivolumab plus ipilimumab continued to provide a long-term, durable survival benefit in patients with or without brain metastases. Intracranial efficacy outcomes favored nivolumab plus ipilimumab versus chemotherapy. These results further support nivolumab plus ipilimumab as an efficacious first-line treatment for patients with metastatic NSCLC, regardless of baseline brain metastasis status.

Published
2023

44. Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis

Author

Bristol Myers Squibb Foundation, Ono Pharmaceutical, Borghaei, Hossein, Ciuleanu, Tudor-Eliade, Lee, Jong-Seok, Pluzanski, Adam, Bernabé Caro, Reyes, Gutierrez, Martin E., Ohe, Yuichiro, Nishio, Makoto, Goldman, Jacki P., Ready, Neal, Spigel, David R., Ramalingam, Suresh S., Paz-Ares, Luis, Gainor, Justin F., Ahmed, Samreen, Reck, Martin, Maio, Michele, O'Byrne, Kenneth J., Memaj, Arteid, Nathan, Faith Ellen, Tran, Phuong, Hellmann, Matthew D., Brahmer, Julie R., Bristol Myers Squibb Foundation, Ono Pharmaceutical, Borghaei, Hossein, Ciuleanu, Tudor-Eliade, Lee, Jong-Seok, Pluzanski, Adam, Bernabé Caro, Reyes, Gutierrez, Martin E., Ohe, Yuichiro, Nishio, Makoto, Goldman, Jacki P., Ready, Neal, Spigel, David R., Ramalingam, Suresh S., Paz-Ares, Luis, Gainor, Justin F., Ahmed, Samreen, Reck, Martin, Maio, Michele, O'Byrne, Kenneth J., Memaj, Arteid, Nathan, Faith Ellen, Tran, Phuong, Hellmann, Matthew D., and Brahmer, Julie R.

Abstract

[Background] First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival., [Patients and methods] Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed., [Results] In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population., [Conclusion] Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

Published
2023

45. Figure S3 from Detection of NRG1 Gene Fusions in Solid Tumors

Author

Jonna, Sushma, primary, Feldman, Rebecca A., primary, Swensen, Jeffrey, primary, Gatalica, Zoran, primary, Korn, Wolfgang M., primary, Borghaei, Hossein, primary, Ma, Patrick C., primary, Nieva, Jorge J., primary, Spira, Alexander I., primary, Vanderwalde, Ari M., primary, Wozniak, Antoinette J., primary, Kim, Edward S., primary, and Liu, Stephen V., primary

Published
2023
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46. Figure S1 from A Phase I, Open-Label Study of Siltuximab, an Anti–IL-6 Monoclonal Antibody, in Patients with B-cell Non-Hodgkin Lymphoma, Multiple Myeloma, or Castleman Disease

Author

Kurzrock, Razelle, primary, Voorhees, Peter M., primary, Casper, Corey, primary, Furman, Richard R., primary, Fayad, Luis, primary, Lonial, Sagar, primary, Borghaei, Hossein, primary, Jagannath, Sundar, primary, Sokol, Lubomir, primary, Usmani, Saad Z., primary, van de Velde, Helgi, primary, Qin, Xiang, primary, Puchalski, Thomas A., primary, Hall, Brett, primary, Reddy, Manjula, primary, Qi, Ming, primary, and van Rhee, Frits, primary

Published
2023
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47. Supplementary Methods from A Phase I, Open-Label Study of Siltuximab, an Anti–IL-6 Monoclonal Antibody, in Patients with B-cell Non-Hodgkin Lymphoma, Multiple Myeloma, or Castleman Disease

Author

Kurzrock, Razelle, primary, Voorhees, Peter M., primary, Casper, Corey, primary, Furman, Richard R., primary, Fayad, Luis, primary, Lonial, Sagar, primary, Borghaei, Hossein, primary, Jagannath, Sundar, primary, Sokol, Lubomir, primary, Usmani, Saad Z., primary, van de Velde, Helgi, primary, Qin, Xiang, primary, Puchalski, Thomas A., primary, Hall, Brett, primary, Reddy, Manjula, primary, Qi, Ming, primary, and van Rhee, Frits, primary

Published
2023
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48. Table from Detection of NRG1 Gene Fusions in Solid Tumors

Author

Jonna, Sushma, primary, Feldman, Rebecca A., primary, Swensen, Jeffrey, primary, Gatalica, Zoran, primary, Korn, Wolfgang M., primary, Borghaei, Hossein, primary, Ma, Patrick C., primary, Nieva, Jorge J., primary, Spira, Alexander I., primary, Vanderwalde, Ari M., primary, Wozniak, Antoinette J., primary, Kim, Edward S., primary, and Liu, Stephen V., primary

Published
2023
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49. Supplementary Table S1 from A Phase I, Open-Label Study of Siltuximab, an Anti–IL-6 Monoclonal Antibody, in Patients with B-cell Non-Hodgkin Lymphoma, Multiple Myeloma, or Castleman Disease

Author

Kurzrock, Razelle, primary, Voorhees, Peter M., primary, Casper, Corey, primary, Furman, Richard R., primary, Fayad, Luis, primary, Lonial, Sagar, primary, Borghaei, Hossein, primary, Jagannath, Sundar, primary, Sokol, Lubomir, primary, Usmani, Saad Z., primary, van de Velde, Helgi, primary, Qin, Xiang, primary, Puchalski, Thomas A., primary, Hall, Brett, primary, Reddy, Manjula, primary, Qi, Ming, primary, and van Rhee, Frits, primary

Published
2023
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