69 results on '"Jamie E. Chaft"'
Search Results
2. Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in PD-(L)1–Monotherapy Pretreated, Advanced Non-Small Cell Lung Cancer: Results From a Phase 1b Clinical Trial
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Edward B. Garon, Alexander I. Spira, Sarah B. Goldberg, Jamie E. Chaft, Vassiliki Papadimitrakopoulou, Tina Cascone, Scott J. Antonia, Julie R. Brahmer, D. Ross Camidge, John D. Powderly, Antoinette J. Wozniak, Enriqueta Felip, Song Wu, Maria L. Ascierto, Nairouz Elgeioushi, and Mark M. Awad
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Pulmonary and Respiratory Medicine ,Oncology - Published
- 2023
3. Effects of Tumor Mutational Burden and Gene Alterations Associated with Radiation Response on Outcomes of Postoperative Radiation Therapy in Non-Small Cell Lung Cancer
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Narek Shaverdian, Annemarie F. Shepherd, Xingzhe Li, Michael Offin, Harry B. Lengel, Daphna Y. Gelblum, Abraham J. Wu, Charles B. Simone, Andreas Rimner, David R. Jones, Jamie E. Chaft, Nadeem Riaz, and Daniel R. Gomez
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Cancer Research ,Kelch-Like ECH-Associated Protein 1 ,Lung Neoplasms ,Radiation ,Oncology ,NF-E2-Related Factor 2 ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Biomarkers, Tumor ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Article - Abstract
Postoperative radiation therapy (PORT) in resected non-small cell lung cancer (NSCLC) improves locoregional outcomes, but recent randomized data do not support its unselected use. We assessed if tumor mutational burden (TMB) and mutations in genes associated with radiation sensitivity can select patients for PORT.Patients with resected NSCLC treated with and without PORT who underwent tumor genomic profiling were examined. The incidence of locoregional failures (LRFs) in patients with deleterious mutations in DNA damage response and repair (DDR) genes and genes associated with radiation resistance (KEAP1/NFE2L2/STK11/PIK3CA) were investigated. Cox modeling and receiver operating characteristic curve (ROC) analysis assessed the relationship between TMB and locoregional control (LRC).Eighty-nine patients with NSCLC treated with PORT were analyzed, with a 2-year LRF rate of 19% (95% confidence interval, 10%-27%). Among patients treated with PORT, those with mutations in radiation resistance genes (n = 16 [18%]) had significantly more LRFs than patients without mutations (2-year LRF rate: 60% vs 11%; P.001). On multivariate analysis, radiation-resistance mutations were associated with LRF after PORT (hazard ratio, 7.42; P.001). Patients with mutations identified in DDR genes (n = 15 [17%]) had significantly improved LRC (P = .048) and no LRF events after PORT. On multivariate analysis, a higher TMB was associated with improved LRC after PORT (hazard ratio, 0.86; P = .01), and TMB was associated with PORT outcomes (area under ROC curve, 0.67-0.77). These genomic markers were not similarly associated with LRF in patients not treated with PORT.The data suggest that patients with radiation-resistance gene alterations may derive minimal benefit from PORT, whereas patients with high TMB and/or alterations in DDR genes may benefit from PORT and be suited for future precision-RT strategies. Prospective studies are necessary to validate these findings.
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- 2022
4. Randomized Phase 2 Placebo-Controlled Trial of Nintedanib for the Treatment of Radiation Pneumonitis
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Andreas Rimner, Zachary R. Moore, Stephanie Lobaugh, Alexander Geyer, Daphna Y. Gelblum, Raja-Elie E. Abdulnour, Annemarie F. Shepherd, Narek Shaverdian, Abraham J. Wu, John Cuaron, Jamie E. Chaft, Marjorie G. Zauderer, Juliana Eng, Gregory J. Riely, Charles M. Rudin, Nicholas Vander Els, Mohit Chawla, Megan McCune, Henry Li, David R. Jones, Dennis M. Sopka, Charles B. Simone, Raymond Mak, Gerald L. Weinhouse, Zhongxing Liao, Daniel R. Gomez, Zhigang Zhang, and Paul K. Paik
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Cancer Research ,Radiation ,Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2023
5. Clinicopathologic outcomes of preoperative targeted therapy in patients with clinical stage I to III non–small cell lung cancer
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Harry B, Lengel, Junting, Zheng, Kay See, Tan, Corinne C, Liu, Bernard J, Park, Gaetano, Rocco, Prasad S, Adusumilli, Daniela, Molena, Helena A, Yu, Gregory J, Riely, Manjit S, Bains, Valerie W, Rusch, Mark G, Kris, Jamie E, Chaft, Bob T, Li, James M, Isbell, and David R, Jones
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Pulmonary and Respiratory Medicine ,Surgery ,Cardiology and Cardiovascular Medicine - Abstract
Targeted therapy improves outcomes in patients with advanced-stage non-small cell lung cancer (NSCLC) and in the adjuvant setting, but data on its use before surgery are limited. We sought to investigate the safety and feasibility of preoperative targeted therapy in patients with operable NSCLC.We retrospectively reviewed 51 patients with clinical stage I to III NSCLC who received targeted therapy, alone or in combination with chemotherapy, before surgical resection with curative intent, treated from 2004 to 2021. The primary outcome was the safety and feasibility of preoperative targeted therapy; secondary outcomes included objective response rate, major pathologic response (defined as ≤10% viable tumor) rate, recurrence-free survival (RFS), and overall survival.Of the 51 patients included, 46 had an activating epidermal growth factor receptor gene alteration and 5 had an anaplastic lymphoma kinase fusion. Overall, 37 of 46 evaluable patients experienced at least 1 adverse event before surgery; however, only 3 patients experienced a grade 3 or 4 event. The objective response rate was 38% (17/45) for all evaluable patients and 44% (14/32) for patients with clinical stage II or III disease. The major pathologic response rate was 20% (9/44); 2 patients had a complete pathologic response. Median RFS was 3.8 years (95% CI, 2.8 to not reached). Targeted therapy alone was associated with better RFS than combination therapy (P = .009) in patients with clinical stage II or III disease.Preoperative targeted therapy was well tolerated and associated with good outcomes, with or without induction chemotherapy. In addition, radiographic response and pathologic response were strongly correlated.
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- 2023
6. Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade
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Joy A. Pai, Matthew D. Hellmann, Jennifer L. Sauter, Marissa Mattar, Hira Rizvi, Hyung Jun Woo, Nisargbhai Shah, Evelyn M. Nguyen, Fathema Z. Uddin, Alvaro Quintanal-Villalonga, Joseph M. Chan, Parvathy Manoj, Viola Allaj, Marina K. Baine, Umesh K. Bhanot, Mala Jain, Irina Linkov, Fanli Meng, David Brown, Jamie E. Chaft, Andrew J. Plodkowski, Mathieu Gigoux, Helen H. Won, Triparna Sen, Daniel K. Wells, Mark T.A. Donoghue, Elisa de Stanchina, Jedd D. Wolchok, Brian Loomis, Taha Merghoub, Charles M. Rudin, Andrew Chow, and Ansuman T. Satpathy
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Cancer Research ,Oncology - Published
- 2023
7. Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non–small cell lung cancer
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Valerie W, Rusch, Alan, Nicholas, G Alexander, Patterson, Salama N, Waqar, Eric M, Toloza, Eric B, Haura, Dan J, Raz, Karen L, Reckamp, Robert E, Merritt, Dwight H, Owen, David J, Finley, Ciaran J, McNamee, Justin D, Blasberg, Edward B, Garon, John D, Mitchell, Robert C, Doebele, Frank, Baciewicz, Misako, Nagasaka, Harvey I, Pass, Katja, Schulze, Ann, Johnson, Paul A, Bunn, Bruce E, Johnson, Mark G, Kris, David J, Kwiatkowski, Ignacio I, Wistuba, Jamie E, Chaft, David P, Carbone, and Jay M, Lee
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Pulmonary and Respiratory Medicine ,Surgery ,Cardiology and Cardiovascular Medicine - Abstract
Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0.From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached.Neoadjuvant atezolizumab in resectable stage IB to IIIB non-small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non-small cell lung cancer.
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- 2023
8. Safety of thoracic radiotherapy in patients with prior immune-related adverse events from immune checkpoint inhibitors
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Andreas Rimner, Daphna Y. Gelblum, Daniel R. Gomez, Abraham J. Wu, Annemarie F. Shepherd, Michael Offin, Narek Shaverdian, Charles B. Simone, Matthew D. Hellmann, Jamie E. Chaft, Jason Beattie, and Maria Thor
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0301 basic medicine ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Adverse effect ,Immune Checkpoint Inhibitors ,Retrospective Studies ,Pneumonitis ,Autoimmune disease ,Lung ,business.industry ,Hematology ,Odds ratio ,medicine.disease ,Radiation Pneumonitis ,Radiation therapy ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,business - Abstract
Background Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are increasingly used to treat advanced cancers. Despite data indicating exaggerated radiation toxicities in patients with autoimmune disease, the safety of thoracic radiotherapy in patients with prior ICI-associated immune-related adverse events (irAEs) is undefined. Patients and methods Patients treated from 2014 to 2020 with ICIs were queried for receipt of corticosteroids and radiotherapy. Patients who received thoracic radiation after symptomatic irAEs were assessed for ≥grade 2 radiation pneumonitis (RP). Characteristics predictive of RP were assessed using logistic regression and response relationships were modeled. Results Among 496 assessed patients, 41 with irAE history subsequently treated with thoracic radiotherapy were analyzed. Most irAEs were grade 2 (n = 21) and 3 (n = 19). Median time from irAE onset to radiotherapy was 8.1 months. Most patients received stereotactic body radiation therapy (n = 20) or hypofractionated radiotherapy (n = 18). In total, 25 patients (61%) developed ≥grade 2 RP at a median of 4 months from radiotherapy and 11 months from onset of irAEs. Three months from RP onset, 16 of 24 (67%) assessable patients had persistent symptoms. Among patients with prior ICI pneumonitis (n = 6), five patients (83%) developed ≥grade 2 RP (grade 2, n = 3; grade ≥3, n = 2). The mean lung radiation dose (MLD) predicted for RP (odds ratio: 1.60, P = 0.00002). The relationship between MLD and RP was strong (area under the receiver-operating characteristic curve: 0.85) and showed an exaggerated dose-response. Among patients with an MLD >5 Gy (n = 26), 21 patients (81%) developed ≥grade 2 RP. Conclusion This is the first study assessing the toxicity of radiotherapy among patients with prior irAEs from ICIs. Patients with prior irAEs were found to be at very high risk for clinically significant and persistent RP from thoracic radiotherapy. Careful consideration should be given to the possibility of an increased risk of RP, and close monitoring is recommended in these patients.
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- 2020
9. COVID-19 in patients with lung cancer
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Alexander Drilon, David Hoyos, M. Offin, Jia Luo, Paul K. Paik, A. Iqbal, Chaitanya Bandlamudi, Kathryn C. Arbour, Matthew D. Hellmann, Marjorie G. Zauderer, Benjamin D. Greenbaum, Marta Łuksza, Mark T.A. Donoghue, Kenneth K.-S. Ng, Bob T. Li, R.M. Daly, Adam J. Schoenfeld, Hira Rizvi, Helena A. Yu, Isabel Ruth Preeshagul, Caroline G. McCarthy, Jamie E. Chaft, Charles M. Rudin, Gregory J Riely, Juliana Eng, Jacklynn V. Egger, Azadeh Namakydoust, W.V. Lai, Mark G. Kris, Christina Falcon, and Piro Lito
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Male ,0301 basic medicine ,Lung Neoplasms ,immunotherapy/ checkpoint blockade ,medicine.medical_treatment ,chemotherapy ,B7-H1 Antigen ,law.invention ,0302 clinical medicine ,law ,Intubation ,Aged, 80 and over ,Hematology ,Middle Aged ,Intensive care unit ,Hospitalization ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Lung cancer ,Coronavirus Infections ,Hydroxychloroquine ,Adult ,medicine.medical_specialty ,Pneumonia, Viral ,macromolecular substances ,Article ,Betacoronavirus ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Pandemics ,Aged ,Retrospective Studies ,Lung ,SARS-CoV-2 ,business.industry ,COVID-19 ,Cancer ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Confidence interval ,COVID-19 Drug Treatment ,small molecule agents ,030104 developmental biology ,business ,Follow-Up Studies - Abstract
Structured Abstract Background Patients with lung cancers may have disproportionately severe COVID-19 outcomes. Understanding the patient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer care during this pandemic. Patients and methods We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n=102) at a single center from March 12-May 6, 2020. Thresholds of severity were defined a priori as hospitalization, ICU/intubation/DNI (a composite metric of severe disease including ICU stay, intubation and invasive mechanical ventilation, and/or transition to do not intubate [DNI]), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. HLA alleles were inferred from MSK-IMPACT (n=46) and compared to controls with lung cancer and no known non-COVID-19 (n=5166). Results COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer-deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease (Odds ratios for severe COVID-19 2.9, 95% CI 1.07-9.44 comparing the median [23.5 pack-years] to never and 3.87, 95% CI 1.35-9.68, respectively). Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. HLA supertypes were generally similar in mild or severe cases of COVID-19 compared to non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. Conclusion COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity., Highlights • COVID-19 is associated with high burden of severity in patients with lung cancer. • Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.
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- 2020
10. Clinical outcomes, local–regional control and the role for metastasis-directed therapies in stage III non-small cell lung cancers treated with chemoradiation and durvalumab
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Abraham J. Wu, Nancy Y. Lee, Andreas Rimner, Zhigang Zhang, Daphna Y. Gelblum, Charles B. Simone, Charles M. Rudin, Daniel R. Gomez, Narek Shaverdian, Matthew D. Hellmann, Annemarie F. Shepherd, Stephanie Lobaugh, Mark G. Kris, Michael Offin, and Jamie E. Chaft
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Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Durvalumab ,Article ,030218 nuclear medicine & medical imaging ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Aged ,Lung ,business.industry ,Incidence (epidemiology) ,Antibodies, Monoclonal ,Chemoradiotherapy ,Hematology ,medicine.disease ,Clinical trial ,Regimen ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Non small cell ,business - Abstract
Background and purpose Concurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined. Materials and methods We reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local–regional and metastatic failures. Results Sixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51–79%) and 85% (95% CI: 75–95%), respectively. The cumulative 12-month incidence of local–regional and distant failures were 18% (95% CI: 5.9–30%) and 30% (95% CI: 16.3–44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS. Conclusions Outcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone.
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- 2020
11. PS01.05 Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis
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Robert E. Merritt, Misako Nagasaka, Eric M. Toloza, Katja Schulze, Jamie E. Chaft, Alan Nicholas, Karen L. Reckamp, V. Rusch, Dan J. Raz, Eric B. Haura, John D. Mitchell, A. Johnson, I. I. Wistuba, Dwight H. Owen, David J. Finley, Frank A. Baciewicz, Alexander Patterson, David P. Carbone, Harvey I. Pass, Justin D. Blasberg, Robert C. Doebele, Jivianne T. Lee, David J. Kwiatkowski, Bruce E. Johnson, S. Phan, Paul A. Bunn, Mark G. Kris, C. Mcnamee, Edward B. Garon, and S. Waqar
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Pulmonary and Respiratory Medicine ,Stage ib ,Oncology ,medicine.medical_specialty ,Atezolizumab ,business.industry ,Internal medicine ,medicine ,business - Published
- 2021
12. FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC
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Luc Dirix, Jamie E. Chaft, Scott N. Gettinger, Marcin Kowanetz, Bo H. Chao, Rodney J. Hicks, Laura Q.M. Chow, Naiyer A. Rizvi, David R. Spigel, Jill Fredrickson, Alan Sandler, Larry Leon, Roel Funke, and Peter Schmid
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Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Phases of clinical research ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,B7-H1 Antigen ,Article ,03 medical and health sciences ,0302 clinical medicine ,Atezolizumab ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Lung cancer ,Adverse effect ,Aged ,Aged, 80 and over ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,030104 developmental biology ,Docetaxel ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Cohort ,Female ,Immunotherapy ,business ,medicine.drug - Abstract
Introduction The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti–programmed death-ligand 1 (PD-L1) atezolizumab in advanced NSCLC selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. Methods Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into cohort 1 (chemotherapy-naive/>6 months between adjuvant chemotherapy and recurrence), cohort 2 (≥ second-line without brain metastases), or cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab on day 1 (21-day cycles). Primary endpoint was investigator-assessed modified Response Evaluation Criteria in Solid Tumors, objective response rate (Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints were overall survival, progression-free survival, duration of response, and safety. Results Patients (N = 138) were enrolled (137 evaluable for response: cohort 1, n = 31; cohort 2, n = 93; and cohort 3, n = 13). Investigator-assessed objective response rate was 32%, 21%, and 23% for cohorts 1, 2, and 3, respectively. Treatment-related adverse events were reported in 81%, 67%, and 69% of patients, respectively, including grade 3–4 treatment-related adverse events in 16%, 19%, and 15%, respectively. Moreover, 88.6% (86 of 97) paired baseline tumor samples had Conclusions Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line. Front-line trials are ongoing, confirming these favorable results.
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- 2018
13. 93TiP MERMAID-2: Phase III study of durvalumab in patients with resected, stage II-III NSCLC who become MRD+ after curative-intent therapy
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D. Harpole, M-J. Ahn, Phillip A. Dennis, Charles Swanton, Christopher Abbosh, Masahiro Tsuboi, David R. Spigel, Helen Mann, Solange Peters, R. May, Fabrice Barlesi, and Jamie E. Chaft
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Pulmonary and Respiratory Medicine ,Oncology ,Curative intent ,medicine.medical_specialty ,Durvalumab ,business.industry ,Internal medicine ,medicine ,In patient ,Stage ii ,business - Published
- 2021
14. Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition
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Abraham J. Wu, R. Dick-Godfrey, Andrew J. Plodkowski, Christopher A. Barker, Donata von Reibnitz, Zhigang Zhang, Robert M. Samstein, Jamie E. Chaft, Andreas Rimner, Kelly Panchoo, Weiji Shi, and Matthew D. Hellmann
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lcsh:Medical physics. Medical radiology. Nuclear medicine ,0301 basic medicine ,medicine.medical_specialty ,Combination therapy ,lcsh:R895-920 ,medicine.medical_treatment ,Thoracic Cancer ,lcsh:RC254-282 ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Clinical endpoint ,Medicine ,Radiology, Nuclear Medicine and imaging ,Adverse effect ,Lung cancer ,Pneumonitis ,Univariate analysis ,business.industry ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,3. Good health ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business ,Esophagitis - Abstract
Purpose The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors. Methods and Materials Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n = 79). Receiving both treatments within 1 month was considered concurrent (n = 35; 44%), and any treatment up to 6 months apart was considered sequential (n = 44; 56%). The primary endpoint of this study was the rate of Grade ≥2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables. Results A total of 79 patients were identified, with lung cancer (n = 45) and melanoma (n = 15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ≥2 AEs included pneumonitis (n = 5; 6%), esophagitis (n = 6; 8%), and dermatitis (n = 8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ≥2 esophagitis (P = .04). Conclusions Overall, Grade ≥2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.
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- 2018
15. Identifying the Optimal Radiation Dose in Locally Advanced Non–Small-cell Lung Cancer Treated With Definitive Radiotherapy Without Concurrent Chemotherapy
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Daphna Y. Gelblum, Zhigang Zhang, Abraham J. Wu, Anish Desai, F. Oro, Weiji Shi, Jamie E. Chaft, Bernice Yan, Andreas Rimner, M. Sonnick, Kenneth E. Rosenzweig, Ellen Yorke, and Paul K. Paik
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Multivariate analysis ,Locally advanced ,Article ,Cigarette Smoking ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Concurrent chemotherapy ,Carcinoma, Non-Small-Cell Lung ,Humans ,Medicine ,Lung cancer ,Definitive radiotherapy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Tumor size ,business.industry ,Radiation dose ,Radiotherapy Dosage ,Chemoradiotherapy ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Tumor Burden ,Oncology ,030220 oncology & carcinogenesis ,Female ,Radiology ,Non small cell ,business ,Nuclear medicine - Abstract
INTRODUCTION: The optimal radiation dose in locally advanced non-small cell lung cancer (NSCLC) is not known for patients who receive sequential chemoradiation or definitive radiation only. Our objective was to determine whether there is a benefit to radiation dose escalation for these patients. METHODS: Patients included in our retrospective analysis received radiation treatment for NSCLC between 2004 and 2013, did not have surgery, and received a dose ≥50.0 Grays (Gy). Patients who received concurrent chemoradiation were excluded from the analysis, leaving 336 patients included. The primary outcomes were overall survival, local failure, and distant failure. RESULTS: On multivariate analysis, after adjusting for age, Karnofsky performance status, gross tumor volume, and treatment modality, patients treated with radiation dose >66 Gy had significantly improved overall survival compared to those treated with 66 Gy had a significantly decreased risk of local failure compared to those treated with 66 Gy versus
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- 2018
16. Corrigendum to 'Clinical utility of next-generation sequencing-based ctDNA testing for common and novel ALK fusions' [Lung Cancer 159 (2021) 66–73]
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Jamie E. Chaft, Yonina R. Murciano-Goroff, Stephen Clarke, Daniel R. Gomez, Malinda Itchins, Ronglai Shen, Seyed Ali Hosseini, Gregory J. Riely, Chongrui Xu, Ryma Benayed, Emily S. Lebow, Hai-Yan Tu, Charles M. Rudin, Michael F. Berger, Maria E. Arcila, Lee P. Lim, David R. Jones, Jorge S. Reis-Filho, Andreas Rimner, Andres Martinez, Alex Makhnin, Caterina Bertucci, Sebastian Mondaca, Mark Li, Pedram Razavi, Tristan Shaffer, Adrian Lee, Azadeh Namakydoust, Nick Pavlakis, James M. Isbell, Michael Offin, Bob T. Li, Gaetano Rocco, and Alexander Drilon
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology ,business.industry ,medicine ,MEDLINE ,Computational biology ,Lung cancer ,medicine.disease ,business ,DNA sequencing - Published
- 2021
17. OA06.06 Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study
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S. Phan, Jamie E. Chaft, Mark G. Kris, David S. Shames, Paul A. Bunn, Alan Nicholas, Justin F. Gainor, A. Johnson, J. Grindheim, V. Rusch, Bruce E. Johnson, Edwin R. Parra, Dwight H. Owen, J. Abel, David P. Carbone, Dan J. Raz, Jivianne T. Lee, David J. Kwiatkowski, F. Oezkan, Alexander Patterson, Gerard Lozanski, Eric B. Haura, Katja Schulze, Karen L. Reckamp, I. I. Wistuba, Christopher J. Rivard, C. Mcnamee, Eric M. Toloza, David J. Finley, Y. Tang, and S. Waqar
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Pulmonary and Respiratory Medicine ,Stage ib ,Clinical biomarker ,Oncology ,medicine.medical_specialty ,business.industry ,Atezolizumab ,Internal medicine ,Medicine ,business - Published
- 2021
18. P03.03 MERMAID-1: A Phase III Study of Adjuvant Durvalumab plus Chemotherapy in Resected NSCLC Patients with MRD+ Post-Surgery
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Jamie E. Chaft, Myung-Ju Ahn, Charles Swanton, Fabrice Barlesi, L. Poole, D. Harpole, David R. Spigel, Solange Peters, R. May, Glenwood D. Goss, Phillip A. Dennis, Masahiro Tsuboi, and C. Abbosh
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Chemotherapy ,Durvalumab ,Oncology ,business.industry ,medicine.medical_treatment ,medicine ,Post surgery ,business ,Adjuvant ,Surgery - Published
- 2021
19. FP04.01 Heart Dose is a Dosimetric Predictor of Overall Survival in Patients with NSCLC Undergoing Post-Operative Radiation Therapy
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Daniel R. Gomez, Brandon S. Imber, Michael Offin, Jonathan E. Leeman, A. Peleg, Daphna Y. Gelblum, Anthony F. Yu, Annemarie F. Shepherd, Charles B. Simone, Abraham J. Wu, Jamie E. Chaft, M. Iocolano, A. Jackson, M. Al-Sadawi, Ellen Yorke, James Huang, Aaron T. Wild, Andreas Rimner, and Narek Shaverdian
- Subjects
Pulmonary and Respiratory Medicine ,Radiation therapy ,medicine.medical_specialty ,Oncology ,business.industry ,medicine.medical_treatment ,Overall survival ,Medicine ,In patient ,Radiology ,Post operative ,business - Published
- 2021
20. Association Between the Early Discontinuation of Durvalumab and Poor Survival in Patients With Stage III NSCLC
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Andreas Rimner, Matthew D. Hellmann, Daniel R. Gomez, Jamie E. Chaft, Michael Offin, Narek Shaverdian, and Annemarie F. Shepherd
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Durvalumab ,Toxicity ,business.industry ,Brief Report ,Stage III NSCLC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,medicine.disease ,Chemoradiation ,Oncology ,Unresected ,Internal medicine ,Cohort ,Medicine ,Stage (cooking) ,Pneumonitis ,business ,Adverse effect ,RC254-282 - Abstract
Introduction: Durvalumab after concurrent chemoradiation (cCRT) has been found to improve outcomes of patients with unresected stage III NSCLC. However, the survival impact of discontinuing durvalumab early owing to adverse events (AEs) remains unknown. Methods: Patients with stage III NSLCC treated with cCRT and greater than or equal to one dose of durvalumab across a multisite cancer center were evaluated. The median durvalumab treatment duration among patients who discontinued owing to AEs (2.1 mo) defined two patient cohorts: early discontinuation (
- Published
- 2021
21. 76 FECAL MICROBIOTA TRANSPLANTATION (FMT) FOR THE TREATMENT OF IMMUNE-MEDIATED DIARRHEA AND COLITIS: A CASE SERIES
- Author
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Matthew D. Hellmann, Jonathan U. Peled, David Faleck, Robin B. Mendelsohn, Paul B. Chapman, Jamie E. Chaft, Robert J. Motzer, Juliana Eng, and Arielle Elkrief
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Diarrhea ,Immune system ,Hepatology ,business.industry ,Immunology ,Gastroenterology ,medicine ,Fecal bacteriotherapy ,Colitis ,medicine.symptom ,medicine.disease ,business - Published
- 2021
22. Definitive Radiotherapy for Local Recurrence of NSCLC After Surgery
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James Huang, Andreas Rimner, Elizabeth Garay, Abraham J. Wu, Jamie E. Chaft, Meier Hsu, Kenneth E. Rosenzweig, A. Foster, and Zhigang Zhang
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Radiosurgery ,Article ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Stage (cooking) ,Lung cancer ,Survival analysis ,Aged ,Aged, 80 and over ,Chemotherapy ,Performance status ,business.industry ,Histology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Surgery ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Introduction Locoregional recurrence after resection of non–small-cell lung cancer (NSCLC) is common. We examined outcomes after definitive radiotherapy (RT) to identify prognostic factors for survival and further recurrence. Patients and Methods We reviewed 152 patients who received RT for locoregional recurrent (LR)-NSCLC, and analyzed subsequent overall survival (OS), locoregional failure (LRF), distant metastasis (DM), and any disease progression (LRF and DM). Results Two- and 5-year OS were 49% and 28%, respectively. Two- and 5-year LRF, DM, and any disease progression rates were 40% and 45%, 33% and 37%, and 53% and 57%, respectively. Performance status and intensity-modulated RT (IMRT) were independently associated with OS, as was RT dose ≥ 60 Gy. Stage, chemotherapy at recurrence, and surgery to recurrence interval were not independently associated with outcome. Chemotherapy at initial presentation, adenocarcinoma histology, and male sex were independently associated with higher rates of DM. Conclusion To our knowledge, this is the largest reported series of LR-NSCLC treated with definitive RT. Survival appears comparable to or greater than that of primary NSCLC. Subsequent LRF is more common than distant failure. Established prognostic factors for primary NSCLC, such as chemotherapy and stage, were not clearly prognostic in this analysis. IMRT and higher RT doses were associated with improved survival, though IMRT patients were also treated more recently. These data support definitive-intent RT with optimal dose and technique in such patients.
- Published
- 2017
23. The Use of Antiangiogenic Agents for Lung Cancer in Elderly Patients: An Expert Panel Discussion Synopsis
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Laura M. Healy, Roman Perez-Soler, Jamie E. Chaft, Corey J. Langer, Mark A. Socinski, Linda Gracie-King, Gregory J. Riely, Deborah L. Middleton, and Benjamin Levy
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Consensus ,Lung Neoplasms ,Angiogenesis Inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Antiangiogenic agents ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lung cancer ,Expert Testimony ,Aged ,Panel discussion ,business.industry ,medicine.disease ,Bevacizumab ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,business - Published
- 2017
24. Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer
- Author
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L. Cambridge, M.K. Kasler, Stephanie Fish, Dennis Stephens, Carlos J. Rodriguez, Hira Rizvi, R. Pollina, Jamie E. Chaft, Juan C. Osorio, Taha Merghoub, Matthew D. Hellmann, Jedd D. Wolchok, Charles M. Rudin, and Ai Ni
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,endocrine system ,medicine.medical_specialty ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,endocrine system diseases ,T-Lymphocytes ,Programmed Cell Death 1 Receptor ,Thyroid Gland ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Hyperthyroidism ,Thyroid function tests ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Humans ,Medicine ,Adverse effect ,Lung cancer ,Aged ,Neoplasm Staging ,biology ,medicine.diagnostic_test ,business.industry ,Thyroid ,Antibodies, Monoclonal ,Cancer ,Original Articles ,Hematology ,Middle Aged ,medicine.disease ,Blockade ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Antibody ,business - Abstract
Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described.Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04).Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.
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- 2017
25. Chemotherapy remains an essential element of personalized care for persons with lung cancers
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Mark G. Kris, Matthew D. Hellmann, Jamie E. Chaft, and Bob T. Li
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Immunoconjugates ,Lung Neoplasms ,medicine.medical_treatment ,Reviews ,Angiogenesis Inhibitors ,Context (language use) ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Immune system ,Drug Therapy ,Internal medicine ,medicine ,Humans ,Precision Medicine ,Lung cancer ,Chemotherapy ,business.industry ,Cancer ,Hematology ,medicine.disease ,Precision medicine ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,Immunotherapy ,business - Abstract
Molecularly targeted and immunotherapies have improved the care of patients with lung cancers. These successes have rallied calls to replace or avoid chemotherapy. Yet, even in this era of precision medicine and exciting advances, cytotoxic chemotherapies remain an essential component of lung cancer treatment. In the setting of locoregional disease, chemotherapy is the only systemic therapy thus far proven to enhance curability when combined with surgery or radiation. In the metastatic setting, chemotherapy can improve the length and quality of life in many patients. Chemotherapy remains the mainstay of care for individuals whose cancers with oncogenic drivers have acquired resistance to targeted agents. Chemotherapy also has the potential to modulate the immune system to enhance the effectiveness of immune checkpoint inhibitors. In this context, chemotherapy should be framed as a critical component of the armamentarium available for optimizing cancer care rather than an unfortunate anachronism. We examine the role of chemotherapy with precision medicine in the current care of patients with lung cancers, as well as opportunities for future integration in combinations with targeted agents, angiogenesis inhibitors, immunotherapies, and antibody drug conjugates.
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- 2016
26. MA11.10 Peripheral T Cell Repertoire Evolution in Resectable NSCLC Treated with Neoadjuvant PD-1 Blockade
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Srinivasan Yegnasubramanian, Tricia R. Cottrell, Patrick M. Forde, Zhicheng Ji, Hok Yee Chan, Valsamo Anagnostou, Ed Gabrielson, Jarushka Naidoo, D. Pardoll, Janis M. Taube, Jamie E. Chaft, M. El Asmar, Jedd D. Wolchok, Hongkai Ji, Haidan Guo, Matthew D. Hellmann, Ni Zhao, Taha Merghoub, Kristen A. Marrone, Joshua E. Reuss, Justina X. Caushi, Julie R. Brahmer, Victor E. Velculescu, Jiajia Zhang, and Kellie N. Smith
- Subjects
Pulmonary and Respiratory Medicine ,T cell repertoire ,Oncology ,business.industry ,Cancer research ,Medicine ,Pd 1 blockade ,business ,Peripheral - Published
- 2019
27. OA13.07 Neoadjuvant Atezolizumab in Resectable NSCLC Patients: Immunophenotyping Results from the Interim Analysis of the Multicenter Trial LCMC3
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L. Fiorillo, Robert D. Suh, I. I. Wistuba, Dwight H. Owen, Alan Nicholas, V. Rusch, S. Phan, Dan J. Raz, Mark G. Kris, Kai He, Rebecca Pearson, Maciej Pietrzak, Katja Schulze, Karen L. Reckamp, Peter J. Kneuertz, Filiz Oezkan, Gerard Lozanski, J. Grindheim, J.H. Cho, Rhonda Kitzler, J.M. Lee, Bruce E. Johnson, Paul A. Bunn, Edward B. Garon, A. Johnson, David P. Carbone, Justin D. Blasberg, R. Banchereau, Jamie E. Chaft, and David J. Kwiatkowski
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Immunophenotyping ,Atezolizumab ,business.industry ,Internal medicine ,Multicenter trial ,medicine ,business ,Interim analysis - Published
- 2019
28. P03.02 Neoadjuvant Osimertinib with/without Chemotherapy vs Chemotherapy for EGFR Mutated Resectable NSCLC: NeoADAURA
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Masahiro Tsuboi, Jamie E. Chaft, Lingmin Zeng, Walter Weder, Andrew Walding, Yasushi Yatabe, C. Escriu, Sanja Dacic, Jing He, and Collin M. Blakely
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Internal medicine ,medicine.medical_treatment ,Medicine ,Osimertinib ,business - Published
- 2021
29. Genomic Analyses for Predictors of Response to Chemoradiation in Stage III Non-Small Cell Lung Cancer
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Andreas Rimner, M. Sonnick, F. Oro, L. Luo, Jamie E. Chaft, Abraham J. Wu, R. Dick-Godfrey, Daniel R. Gomez, Robert M. Samstein, Narek Shaverdian, C. Wang, Paul K. Paik, and Baho Sidiqi
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,Oncology ,medicine.medical_specialty ,DNA damage ,lcsh:R895-920 ,medicine.medical_treatment ,lcsh:RC254-282 ,DNA sequencing ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Scientific Article ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Gene ,Chemotherapy ,Proportional hazards model ,business.industry ,Hazard ratio ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030220 oncology & carcinogenesis ,Cohort ,business - Abstract
Background: Radiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy. Methods: We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing. Results: 110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between AKT2 mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7, P = .003 and P = .003, respectively). Analyses restricted to loss-of-function mutations identified KMT2C and KMT2D deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, P < .001 and P < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, P = .049). Conclusions: This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in AKT2, KMT2C, and KMT2D as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.
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- 2021
30. A Pre-Treatment PET And CT-Derived Model for Progression-Free Survival in Early Stage Non-Small Cell Lung Cancer
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Joseph O. Deasy, Abraham J. Wu, Saad Nadeem, Daphna Y. Gelblum, K.J. Fitzgerald, Andreas Rimner, Ellen Yorke, Aditi Iyer, A. Apte, Wookjin Choi, Maria Thor, Michael Offin, J.H. Oh, and Jamie E. Chaft
- Subjects
Oncology ,Pre treatment ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.disease ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Progression-free survival ,Non small cell ,Stage (cooking) ,Lung cancer ,business - Published
- 2020
31. Durvalumab with Concurrent Definitive Radiation Therapy (DART) for Locally-Advanced Non-Small Cell Lung Cancer - A Phase II Study
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D. McKnight, M. Mccune, Andreas Rimner, Rupesh Kotecha, B. Patson, H. Li, Jamie E. Chaft, Narek Shaverdian, Daniel R. Gomez, and Michael Offin
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,Durvalumab ,business.industry ,Locally advanced ,Phases of clinical research ,medicine.disease ,Definitive Radiation Therapy ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Non small cell ,Lung cancer ,business - Published
- 2020
32. One-Year Disease Outcomes in Stage III Non-Small Cell Lung Cancers Treated with Trimodality Therapy vs Concurrent Chemoradiation and Durvalumab
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Abraham J. Wu, Charles B. Simone, Daphna Y. Gelblum, David R. Jones, Andreas Rimner, Annemarie F. Shepherd, Zhigang Zhang, Stephanie Lobaugh, Daniel R. Gomez, Charles M. Rudin, Michael Offin, James M. Isbell, Narek Shaverdian, Mark G. Kris, Jamie E. Chaft, and Matthew D. Hellmann
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,Durvalumab ,Lung ,business.industry ,Disease outcome ,Concurrent chemoradiation ,medicine.anatomical_structure ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Non small cell ,Stage (cooking) ,business - Published
- 2020
33. Final Results of a Phase I Trial of Stereotactic Body Radiotherapy for Larger (>3cm) Inoperable Non-Small Cell Lung Cancer
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Abraham J. Wu, Si-Yuan Zhang, John J. Cuaron, D. von Reibnitz, Andreas Rimner, E. Gelb, Ellen Yorke, Jamie E. Chaft, Daphna Y. Gelblum, and Kenneth K.-S. Ng
- Subjects
Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Phase (waves) ,medicine.disease ,Oncology ,Medicine ,Radiology, Nuclear Medicine and imaging ,Non small cell ,Radiology ,business ,Lung cancer ,Stereotactic body radiotherapy - Published
- 2020
34. HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers
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Maria E. Arcila, Dara L. Aisner, Meier Hsu, Jamie E. Chaft, Dara S. Ross, Marileila Varella-Garcia, Bob T. Li, Mark G. Kris, and Severine Kako
- Subjects
0301 basic medicine ,Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Receptor, ErbB-2 ,Adenocarcinoma of Lung ,Biology ,Adenocarcinoma ,medicine.disease_cause ,Article ,03 medical and health sciences ,Exon ,symbols.namesake ,0302 clinical medicine ,medicine ,Humans ,Molecular Targeted Therapy ,skin and connective tissue diseases ,Lung cancer ,neoplasms ,Genotyping ,In Situ Hybridization, Fluorescence ,Aged ,Sanger sequencing ,Mutation ,medicine.diagnostic_test ,Gene Amplification ,Cancer ,Genes, erbB-2 ,Middle Aged ,medicine.disease ,Molecular biology ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,symbols ,Immunohistochemistry ,Female ,Fluorescence in situ hybridization - Abstract
Introduction Human epidermal growth factor receptor 2 gene (HER2 [also known as ERBB2]) alterations have been identified as oncogenic drivers and potential therapeutic targets in lung cancers. The molecular associations of HER2 gene amplification, mutation, and HER2 protein overexpression in lung cancers have not been distinctly defined. To explore these associations, Memorial Sloan Kettering Cancer Center and the University of Colorado combined their data on HER2 alterations in lung cancers. Methods Tumor specimens from 175 patients with lung adenocarcinomas and no prior targeted therapy were evaluated for the presence of HER2 amplification and mutation and HER2 protein overexpression. Amplification was assessed by fluorescence in situ hybridization (FISH) and defined as an HER2-to-chromosome enumeration probe 17 ratio of at least 2.0. Mutation was assessed by fragment analysis, mass spectrometry genotyping, and Sanger sequencing. Overexpression was assessed by immunohistochemical (IHC) staining. The frequencies of HER2 amplification and mutation and HER2 overexpression were calculated and their overlap examined. Results HER2 amplification was detected by FISH in 5 of 175 cases (3%). HER2 mutation was detected in 4 of 148 specimens (3%), including three identical 12–base pair insertions (p.A775_G776insYVMA) and a 9–base pair insertion, all in exon 20. None of the HER2-mutant cases was amplified. HER2 overexpression (2+ or 3+) on IHC staining was not detected in the 25 specimens available for testing, and negative IHC staining correlated with the negative results according to FISH. Conclusions HER2 mutations are not associated with HER2 amplification, thus suggesting a distinct entity and therapeutic target. HER2-positive lung cancer may not be an adequate term, and patient cohorts for the study of HER2-targeted agents should be defined by the specific HER2 alteration present.
- Published
- 2016
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35. Utility of Routine PET Imaging to Predict Response and Survival After Induction Therapy for Non-Small Cell Lung Cancer
- Author
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Tim Akhurst, Bernard J. Park, Robert J. Downey, Stephen A. Barnett, Valerie W. Rusch, Jamie E. Chaft, Ronglai Shen, Gabriel Plourde, and Junting Zheng
- Subjects
Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,New York ,Standardized uptake value ,Article ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Combined Modality Therapy ,Postoperative Period ,Lung cancer ,Survival rate ,Neoplasm Staging ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Induction chemotherapy ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Clinical trial ,030104 developmental biology ,Positron emission tomography ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Predictive value of tests ,Female ,Surgery ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Data from clinical trials suggest that changes in the glucose avidity of the primary site of lung cancer during induction therapy, measured by changes in 18 F-fluorodeoxyglucose positron emission tomography, correlate with tumor response. Little information about the utility of changes in positron emission tomography imaging of involved lymph nodes during induction chemotherapy is available. The utility of positron emission tomography imaging of either the primary site or nodal metastases, obtained during routine clinical care outside of a clinical trial setting, to predict response has also not been examined. Methods A retrospective review of all surgical patients with non-small cell lung cancer at a single institution imaged between 2000 and 2006 with 18 F-fluorodeoxyglucose positron emission tomography before or after induction therapy was performed. Results An increase in standardized uptake value in the primary site of disease during induction therapy was associated with reduced overall survival after resection. Neither pretreatment standardized uptake value nor percentage change in the primary site was associated with overall survival after resection. A decrease in standardized uptake value of greater than 60% in the involved N2 mediastinal nodes was the best predictor of overall survival, better than changes seen in the primary site of disease. Conclusions An increase in glucose avidity of non-small cell lung cancers during induction therapy was associated with a worse prognosis compared with stable or any decrease in standardized uptake value. Changes in the glucose avidity of mediastinal nodal metastases may be a stronger predictor of survival than changes in the primary site of disease.
- Published
- 2016
36. Impact of Concurrent PIK3CA Mutations on Response to EGFR Tyrosine Kinase Inhibition in EGFR-Mutant Lung Cancers and on Prognosis in Oncogene-Driven Lung Adenocarcinomas
- Author
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Andrew J. Plodkowski, Jamie E. Chaft, Maria E. Arcila, Kaitlin M. Woo, Mark G. Kris, Marc Ladanyi, Camelia S. Sima, Alexander Drilon, Matthew D. Hellmann, and Juliana Eng
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Class I Phosphatidylinositol 3-Kinases ,Mutant ,Adenocarcinoma of Lung ,Adenocarcinoma ,PIK3CA mutation ,medicine.disease_cause ,Article ,Phosphatidylinositol 3-Kinases ,medicine ,Humans ,Neoplasm ,Epidermal growth factor receptor ,Protein Kinase Inhibitors ,neoplasms ,Aged ,Aged, 80 and over ,Tyrosine kinase inhibitors ,Mutation ,Oncogene ,biology ,medicine.diagnostic_test ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,respiratory tract diseases ,ErbB Receptors ,Oncology ,Drug Resistance, Neoplasm ,Cancer research ,biology.protein ,Female ,EGFR-mutant lung adenocarcinomas ,KRAS ,business ,Fluorescence in situ hybridization - Abstract
Introduction In patients with epidermal growth factor receptor (EGFR) -mutant or KRAS -mutant lung adenocarcinomas, the prognostic impact of a concurrent PIK3CA mutation remains unclear. Although preclinical data suggest that sensitivity to EGFR tyrosine kinase inhibition (TKI) is decreased in EGFR -mutant lung cancers also harboring a PIK3CA mutation, this interaction has not been explored clinically. Methods Patients with lung adenocarcinomas harboring a PIK3CA mutation concurrent with a separate driver mutation were identified through mutational hotspot testing, multiplex sizing assays, and fluorescence in situ hybridization. Overall survival and outcomes with EGFR TKI monotherapy ( EGFR -mutant) were estimated using Kaplan–Meier methods and compared between double-mutant ( EGFR -mutant or KRAS -mutant, concurrent PIK3CA -mutant) and single-mutant patients ( EGFR -mutant or KRAS -mutant, PIK3CA wild-type) using log-rank tests. Results In EGFR -mutant and KRAS -mutant lung cancers, a concurrent PIK3CA mutation was associated with a decrease in median overall survival: 18 versus 33 months ( EGFR double mutant, n=10 versus single mutant, n=43, p = 0.006), and 9 versus 16 months ( KRAS double mutant, n=16 versus single mutant, n=47, p = 0.020). In EGFR -mutant lung cancers, a concurrent PIK3CA mutation did not impact benefit from EGFR TKI monotherapy. Single versus double mutant: objective response rate, 83% (n = 29) versus 62% (n = 6, p = 0.80); median time to progression, 11 (n = 29) versus 8 months (n = 6, p = 0.84); and median duration of TKI therapy, 15 (n = 32) versus 15 months (n = 10, p = 0.65). Conclusion A concurrent PIK3CA mutation is a poor prognostic factor in patients with advanced EGFR -mutant or KRAS -mutant lung adenocarcinomas. There was no evidence that clinical benefit from EGFR TKI monotherapy is affected by a concurrent PIK3CA mutation in EGFR -mutant lung cancers.
- Published
- 2015
37. P2.04-88 Surgical Outcomes of a Multicenter Phase II Trial of Neoadjuvant Atezolizumab in Resectable Stages IB-IIIB NSCLC: Update on LCMC3 Clinical Trial
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Mark G. Kris, David J. Finley, S. Phan, Frank A. Baciewicz, Katja Schulze, S. Waqar, Alan Nicholas, A. Johnson, Karen L. Reckamp, V. Rusch, John D. Mitchell, Jamie E. Chaft, David P. Carbone, Justin D. Blasberg, Robert E. Merritt, Eric M. Toloza, J.M. Lee, Harvey I. Pass, G. Patterson, Dan J. Raz, I. I. Wistuba, Robert C. Doebele, David J. Kwiatkowski, Edward B. Garon, Paul A. Bunn, Bruce E. Johnson, Misako Nagasaka, Dwight H. Owen, Eric B. Haura, and C. Mcnamee
- Subjects
Pulmonary and Respiratory Medicine ,Clinical trial ,Oncology ,medicine.medical_specialty ,Atezolizumab ,business.industry ,Internal medicine ,medicine ,business - Published
- 2019
38. P2.04-24 Transcriptional Profiling of Neoantigen Specific T Cells in Resectable NSCLC Treated with Neoadjuvant Anti-PD-1
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Julie R. Brahmer, Srinivasan Yegnasubramanian, Janis M. Taube, Tricia R. Cottrell, Jarushka Naidoo, Hok Yee Chan, Zhicheng Ji, Justina X. Caushi, Patrick M. Forde, Edward Gabrielson, Taha Merghoub, Kellie N. Smith, M. El Asmar, Kristen A. Marrone, Jamie E. Chaft, Haidan Guo, J. Zhang, Matthew D. Hellmann, Ni Zhao, Hongkai Ji, Victor E. Velculescu, Valsamo Anagnostou, D. Pardoll, and Jedd D. Wolchok
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,business.industry ,Anti pd 1 ,Cancer research ,Medicine ,business - Published
- 2019
39. P1.17-08 Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer
- Author
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F. Oro, R. Dick-Godfrey, Abraham J. Wu, L. Luo, Andreas Rimner, M. Sonnick, R. Samstein, Baho Sidiqi, C. Wang, Jamie E. Chaft, and Paul K. Paik
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,business ,Stage III Non-Small Cell Lung Cancer - Published
- 2018
40. P1.16-47 Adjuvant Targeted Therapy Following Standard Adjuvant Therapy for Resected NSCLC: An Initial Report from ALCHEMIST (Alliance A151216)
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Karen Kelly, Phillip Joseph La Stella, S. Malik, S.S. Ramalingam, K. Tazi, Jamie E. Chaft, A.D. Tan, David R. Gandara, C. Watt, Sumithra J. Mandrekar, M. Faggen, Geoffrey R. Oxnard, Shauna L. Hillman, David E. Gerber, Tom Stinchcombe, Suzanne E. Dahlberg, Ramaswamy Govindan, and Dennis A. Wigle
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Internal medicine ,Adjuvant therapy ,Medicine ,business ,Adjuvant ,Targeted therapy - Published
- 2018
41. Phase II Study of the GI-4000 KRAS Vaccine After Curative Therapy in Patients With Stage I-III Lung Adenocarcinoma Harboring a KRAS G12C, G12D, or G12V Mutation
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Claire Coeshott, Sandra P. D'Angelo, Alicia Mattson, Jamie E. Chaft, Valerie W. Rusch, Mark G. Kris, Payal R. Patel, Lee M. Krug, Anya Litvak, Maria E. Arcila, David Apelian, Christopher G. Azzoli, and Bernard J. Park
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,T-Lymphocytes ,Phases of clinical research ,Saccharomyces cerevisiae ,Adenocarcinoma ,Lymphocyte Activation ,medicine.disease_cause ,Cancer Vaccines ,GTP-Binding Protein alpha Subunits, G12-G13 ,Proto-Oncogene Proteins p21(ras) ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Stage (cooking) ,Lung cancer ,Adverse effect ,Cells, Cultured ,Aged ,Neoplasm Staging ,business.industry ,Middle Aged ,medicine.disease ,Consolidation Chemotherapy ,Vaccination ,Treatment Outcome ,Mutation ,Immunology ,ras Proteins ,Female ,KRAS ,business - Abstract
Introduction Patients with early-stage lung cancer have a high risk of recurrence despite multimodality therapy. KRAS-mutant lung adenocarcinomas are the largest genetically defined subgroup, representing 25% of patients. GI-4000 is a heat-killed recombinant Saccharomyces cerevisiae yeast–derived vaccine expressing mutant KRAS proteins. The present phase II study assessed the feasibility, immunogenicity, and safety of the GI-4000 vaccine in patients with early-stage, KRAS-mutant lung cancer. Materials and Methods Patients with stage I-III KRAS-mutant lung cancer who completed curative therapy were enrolled. The patients received the genotype matched GI-4000 vaccine for ≤ 3 years or until intolerance, disease recurrence, or death. The KRAS antigen T-cell response was assessed using the interferon-gamma enzyme-linked immunospot assay in peripheral blood mononuclear cells. The study was powered to detect an immune response in ≥ 25% of patients. Results A total of 24 patients were enrolled over 28 months. No vaccine-related serious adverse events occurred. One patient withdrew consent because of pain at the injection site. The study met its primary endpoint, with 50% of patients developing an immune response to mutant KRAS. The median number of vaccinations received was 15 (range, 1-19). Ten patients experienced disease recurrence, and 6 died. Compared with the genotypically matched historical controls, the recurrence rates were equivalent but overall survival showed a favorable trend. Conclusion GI-4000 was well tolerated and immunogenic when used as consolidation therapy in patients with stage I-III KRAS-mutant lung cancer. The patterns of recurrence and death observed in the present study can be used to design a randomized study of GI-4000 with overall survival as the primary endpoint.
- Published
- 2014
42. HER2 insertion YVMA mutant lung cancer: Long natural history and response to afatinib
- Author
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Nick Pavlakis, Maria E. Arcila, Adrian Lee, Mark G. Kris, Wendy A Cooper, Jamie E. Chaft, Sandra A O'Toole, Bing Yu, and Bob T. Li
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Receptor, ErbB-2 ,Afatinib ,medicine.medical_treatment ,Mutant ,Antineoplastic Agents ,medicine.disease_cause ,Article ,Targeted therapy ,Exon ,medicine ,Humans ,skin and connective tissue diseases ,Lung cancer ,Protein Kinase Inhibitors ,neoplasms ,Mutation ,Lung ,business.industry ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Mutagenesis, Insertional ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Quinazolines ,Cancer research ,Tomography, X-Ray Computed ,business ,medicine.drug - Abstract
Human epidermal growth factor 2 (HER2, ERBB2) mutations in lung cancers are oncogenic drivers that respond to HER2 targeted therapies. Little is known about the sensitivity of subtypes of HER2 mutant lung cancers to targeted agents. We present a patient with HER2 mutant lung cancer with a 12 base pair insertion YVMA (p.A775_G776insYVMA), who had a long natural history and durable partial response to afatinib. We demonstrate that afatinib has activity in patients with HER2 mutant lung cancers with exon 20 YVMA insertions, the most common variant.
- Published
- 2015
43. Serpins Promote Cancer Cell Survival and Vascular Co-Option in Brain Metastasis
- Author
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Xiang Zhang, Jamie E. Chaft, Anna C. Obenauf, Derek J. Lee, Qing Chen, Edi Brogi, Mark G. Kris, Xin Jin, Jason T. Huse, Joan Massagué, and Manuel Valiente
- Subjects
Fas Ligand Protein ,Lung Neoplasms ,Cell Survival ,Mice, Nude ,Breast Neoplasms ,Neural Cell Adhesion Molecule L1 ,Adenocarcinoma ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Plasminogen Activators ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,Breast cancer ,Neuroserpin ,Cell Line, Tumor ,Plasminogen Activator Inhibitor 2 ,medicine ,Animals ,Humans ,Fibrinolysin ,Lung cancer ,Serpins ,030304 developmental biology ,0303 health sciences ,Biochemistry, Genetics and Molecular Biology(all) ,Brain Neoplasms ,Carcinoma ,Neuropeptides ,Brain ,Cancer ,medicine.disease ,3. Good health ,Disease Models, Animal ,Astrocytes ,030220 oncology & carcinogenesis ,Immunology ,Cancer cell ,Cancer research ,Female ,Brain metastasis - Abstract
SummaryBrain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers.
- Published
- 2014
44. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint
- Author
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Matthew D, Hellmann, Jamie E, Chaft, William N, William, Valerie, Rusch, Katherine M W, Pisters, Neda, Kalhor, Apar, Pataer, William D, Travis, Stephen G, Swisher, Mark G, Kris, and Ara, Vaporciyan
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,Lung Neoplasms ,business.industry ,Surrogate endpoint ,medicine.medical_treatment ,medicine.disease ,Neoadjuvant Therapy ,Surgery ,Clinical trial ,Major Pathologic Response ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Carcinoma ,Clinical endpoint ,Humans ,Medicine ,business ,Prospective cohort study ,Biomarkers ,Neoadjuvant therapy ,Neoplasm Staging - Abstract
Improvements in outcomes for patients with resectable lung cancers have plateaued. Clinical trials of resectable non-small-cell lung cancers with overall survival as the primary endpoint require a decade or longer to complete, are expensive, and limit innovation. A surrogate for survival, such as pathological response to neoadjuvant chemotherapy, has the potential to improve the efficiency of trials and expedite advances. 10% or less residual viable tumour after neoadjuvant chemotherapy, termed here major pathological response, meets criteria for a surrogate; major pathological response strongly associates with improved survival, is reflective of treatment effect, and captures the magnitude of the treatment benefit on survival. We support the incorporation of major pathological response as a surrogate endpoint for survival in future neoadjuvant trials of resectable lung cancers. Additional prospective studies are needed to confirm the validity and reproducibility of major pathological response within individual histological and molecular subgroups and with new drugs.
- Published
- 2014
45. Real-World Evaluation of Consolidative Durvalumab in Locally Advanced Non-Small-Cell Lung Cancer Treated with Definitive Chemoradiation
- Author
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Isabel Ruth Preeshagul, Abraham J. Wu, Narek Shaverdian, Nancy Y. Lee, Annemarie F. Shepherd, Andreas Rimner, Daniel R. Gomez, Jamie E. Chaft, Stephanie Lobaugh, Joseph O. Deasy, Zhigang Zhang, Michael Offin, Daphna Y. Gelblum, and Matthew D. Hellmann
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,Durvalumab ,business.industry ,Locally advanced ,medicine.disease ,Internal medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,Non small cell ,business ,Lung cancer - Published
- 2019
46. Predicting Tumor Progression in Early Stage Non-small Cell Lung Cancer Using Pre-treatment Imaging
- Author
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Abraham J. Wu, Michael Offin, Andreas Rimner, Joseph O. Deasy, Jamie E. Chaft, Maria Thor, A. Apte, J.H. Oh, Daphna Y. Gelblum, K.J. Fitzgerald, and Aditi Iyer
- Subjects
Oncology ,Pre treatment ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.disease ,Tumor progression ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Non small cell ,Stage (cooking) ,business ,Lung cancer - Published
- 2019
47. A Comparison of Trimodality Therapy Versus Definitive Concurrent Chemoradiation in Patients With Stage IIIA Non–small Cell Lung Cancer
- Author
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Abraham J. Wu, Annemarie F. Shepherd, Brandon S. Imber, Jonathan E. Leeman, Daphna Y. Gelblum, Andreas Rimner, X. Pei, E. Gelb, James M. Isbell, Ellen Yorke, Jamie E. Chaft, and Aaron T. Wild
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Stage IIIA Non-Small Cell Lung Cancer ,Concurrent chemoradiation ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,business - Published
- 2017
48. Tumor Spread through Airspaces and Histologic Subtype Predict Outcomes Following Post-operative Radiation Therapy for Locally Advanced Lung Adenocarcinoma
- Author
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Prasad S. Adusumilli, Brandon S. Imber, Jonathan E. Leeman, David R. Jones, E. Gelb, X. Pei, Andreas Rimner, William D. Travis, James M. Isbell, Abraham J. Wu, Ellen Yorke, Borys Mychalczak, Annemarie F. Shepherd, Jamie E. Chaft, and Aaron T. Wild
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,Lung ,business.industry ,medicine.medical_treatment ,Locally advanced ,medicine.disease ,Radiation therapy ,medicine.anatomical_structure ,Internal medicine ,medicine ,Adenocarcinoma ,Radiology, Nuclear Medicine and imaging ,Radiology ,Post operative ,business - Published
- 2017
49. Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer
- Author
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L. Luo, Robert M. Samstein, Andreas Rimner, M. Sonnick, Abraham J. Wu, Jamie E. Chaft, F. Oro, R. Dick-Godfrey, and Paul K. Paik
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,business ,Stage III Non-Small Cell Lung Cancer - Published
- 2018
50. MA04.11 Neoantigen Targeting and T Cell Reshaping in Resectable NSCLC Patients Treated with Neoadjuvant PD-1 Blockade
- Author
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Julie R. Brahmer, Haidan Guo, Matthew D. Hellmann, Patrick M. Forde, Valsamo Anagnostou, D. Pardoll, Victor E. Velculescu, M. El Asmar, Tricia R. Cottrell, Taha Merghoub, Zhicheng Ji, Jiajia Zhang, Janis M. Taube, Justina X. Caushi, Jarushka Naidoo, Hongkai Ji, Prerna Suri, Kristen A. Marrone, Jamie E. Chaft, Kellie N. Smith, and Hok Yee Chan
- Subjects
Pulmonary and Respiratory Medicine ,medicine.anatomical_structure ,Oncology ,business.industry ,T cell ,Cancer research ,Pd 1 blockade ,Medicine ,business - Published
- 2018
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