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Targeted Therapies and Surgical Resection for Lung Cancer: Evolving Treatment Options
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Saadia A. Faiz, MD, FCCP

Click to view more from Pulmonology Data Trends 2024. 

References
  1. American Cancer Society. Key statistics for lung cancer. Revised January 29, 2024. Accessed June 10, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
  2. Drilon A, Camidge DR, Lin JJ, et al; for the TRIDENT-1 Investigators. Repotrectinib in ROS1 fusion-positive non-small-cell lung cancer. N Engl J Med. 2024;390(2):118-131. doi:10.1056/NEJMoa2302299
  3. Wu YL, Dziadziuszko R, Ahn JS, et al; for the ALINA Investigators. Alectinib in resected ALK-positive non-small-cell lung cancer. N Engl J Med. 2024;390(14):1265-1276.
  4. Mulligan L. Selective RET kinase inhibitors and lung cancer. N Engl J Med. 2023;389(20):1913-1916. doi:10.1056/NEJMe2311295                                                                                                 
  5. Zhou C, Soloman B, Loong HH, et al; for the LIBRETTO-432 Trial Investigators. First-line selpercatinib or chemotherapy and pembrolizumab in RET fusion-positive NSCLC. N Engl J Med. 2023:389(20):1839-1850. doi:10.1056/NEJMoa239457
  6. Vaccaro K, Allen J, Whitfield TW, et al. Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction. bioRxiv. Preprint posted online March 6, 2023. doi:10.1101/2023.03.03.531059
  7. Liu M, Hu S, Yan N, Popowski KD, Cheng K. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat Nanotechnol. 2024;19(4):565-575. doi:10.1038/s41565-023-01580-3
  8. Altorki N, Wang X, Kozono D, et al. Lobar or sublobar resection for peripheral stage IA non-small-cell lung cancer. N Engl J Med. 2023;388(6):489-498. doi:10.1056/NEJMoa2212083
  9. Koike T, Hasebe T, Nakamura M, Shimizu Y, Goto T, Tsuchida M. Towards better outcomes: segmentectomy for ground-glass opacity-dominant non-small cell lung cancer 3 cm or less─insights form JCOG1211 [editorial commentary]. AME Clin Trials Rev. 2023;1:5. doi:10.21037/actr-23-10
  10. Aokage K, Suzuki K, Saji H, et al; for the Japan Clinical Oncology Group. Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including groundglass opacity (JCOG1211): a multicentre, single-arm, confirmatory phase 3 trial. Lancet Respir Med. 2023;11(6):540-549. doi:10.1016/S2213-2600(23)00041-3    
  11. Mandula JK, Sierra-Mondragon RA, Jimenez RV, et al. Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages. Immunity. 2024;57(5):1124-1140.e9. doi:10.1016/j.immuni.2024.03.020

 

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Saadia A. Faiz, MD, FCCP
Professor, Department of Pulmonary Medicine
The University of Texas
Physician
MD Anderson Cancer Center
Houston, TX

Dr. Faiz serve(d) as director, officer, partner, employee, advisor, consultant, or trustee for: Medscape. Medscape and MDedge are both part of the Medscape Professional Network.

Publications
MDedge Internal Medicine
CHEST Physician
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Lung Cancer
Author(s)
Saadia A. Faiz, MD, FCCP
Author(s)
Saadia A. Faiz, MD, FCCP
Author and Disclosure Information

Saadia A. Faiz, MD, FCCP
Professor, Department of Pulmonary Medicine
The University of Texas
Physician
MD Anderson Cancer Center
Houston, TX

Dr. Faiz serve(d) as director, officer, partner, employee, advisor, consultant, or trustee for: Medscape. Medscape and MDedge are both part of the Medscape Professional Network.

Author and Disclosure Information

Saadia A. Faiz, MD, FCCP
Professor, Department of Pulmonary Medicine
The University of Texas
Physician
MD Anderson Cancer Center
Houston, TX

Dr. Faiz serve(d) as director, officer, partner, employee, advisor, consultant, or trustee for: Medscape. Medscape and MDedge are both part of the Medscape Professional Network.

Click to view more from Pulmonology Data Trends 2024. 

Click to view more from Pulmonology Data Trends 2024. 

References
  1. American Cancer Society. Key statistics for lung cancer. Revised January 29, 2024. Accessed June 10, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
  2. Drilon A, Camidge DR, Lin JJ, et al; for the TRIDENT-1 Investigators. Repotrectinib in ROS1 fusion-positive non-small-cell lung cancer. N Engl J Med. 2024;390(2):118-131. doi:10.1056/NEJMoa2302299
  3. Wu YL, Dziadziuszko R, Ahn JS, et al; for the ALINA Investigators. Alectinib in resected ALK-positive non-small-cell lung cancer. N Engl J Med. 2024;390(14):1265-1276.
  4. Mulligan L. Selective RET kinase inhibitors and lung cancer. N Engl J Med. 2023;389(20):1913-1916. doi:10.1056/NEJMe2311295                                                                                                 
  5. Zhou C, Soloman B, Loong HH, et al; for the LIBRETTO-432 Trial Investigators. First-line selpercatinib or chemotherapy and pembrolizumab in RET fusion-positive NSCLC. N Engl J Med. 2023:389(20):1839-1850. doi:10.1056/NEJMoa239457
  6. Vaccaro K, Allen J, Whitfield TW, et al. Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction. bioRxiv. Preprint posted online March 6, 2023. doi:10.1101/2023.03.03.531059
  7. Liu M, Hu S, Yan N, Popowski KD, Cheng K. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat Nanotechnol. 2024;19(4):565-575. doi:10.1038/s41565-023-01580-3
  8. Altorki N, Wang X, Kozono D, et al. Lobar or sublobar resection for peripheral stage IA non-small-cell lung cancer. N Engl J Med. 2023;388(6):489-498. doi:10.1056/NEJMoa2212083
  9. Koike T, Hasebe T, Nakamura M, Shimizu Y, Goto T, Tsuchida M. Towards better outcomes: segmentectomy for ground-glass opacity-dominant non-small cell lung cancer 3 cm or less─insights form JCOG1211 [editorial commentary]. AME Clin Trials Rev. 2023;1:5. doi:10.21037/actr-23-10
  10. Aokage K, Suzuki K, Saji H, et al; for the Japan Clinical Oncology Group. Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including groundglass opacity (JCOG1211): a multicentre, single-arm, confirmatory phase 3 trial. Lancet Respir Med. 2023;11(6):540-549. doi:10.1016/S2213-2600(23)00041-3    
  11. Mandula JK, Sierra-Mondragon RA, Jimenez RV, et al. Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages. Immunity. 2024;57(5):1124-1140.e9. doi:10.1016/j.immuni.2024.03.020

 

References
  1. American Cancer Society. Key statistics for lung cancer. Revised January 29, 2024. Accessed June 10, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
  2. Drilon A, Camidge DR, Lin JJ, et al; for the TRIDENT-1 Investigators. Repotrectinib in ROS1 fusion-positive non-small-cell lung cancer. N Engl J Med. 2024;390(2):118-131. doi:10.1056/NEJMoa2302299
  3. Wu YL, Dziadziuszko R, Ahn JS, et al; for the ALINA Investigators. Alectinib in resected ALK-positive non-small-cell lung cancer. N Engl J Med. 2024;390(14):1265-1276.
  4. Mulligan L. Selective RET kinase inhibitors and lung cancer. N Engl J Med. 2023;389(20):1913-1916. doi:10.1056/NEJMe2311295                                                                                                 
  5. Zhou C, Soloman B, Loong HH, et al; for the LIBRETTO-432 Trial Investigators. First-line selpercatinib or chemotherapy and pembrolizumab in RET fusion-positive NSCLC. N Engl J Med. 2023:389(20):1839-1850. doi:10.1056/NEJMoa239457
  6. Vaccaro K, Allen J, Whitfield TW, et al. Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction. bioRxiv. Preprint posted online March 6, 2023. doi:10.1101/2023.03.03.531059
  7. Liu M, Hu S, Yan N, Popowski KD, Cheng K. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat Nanotechnol. 2024;19(4):565-575. doi:10.1038/s41565-023-01580-3
  8. Altorki N, Wang X, Kozono D, et al. Lobar or sublobar resection for peripheral stage IA non-small-cell lung cancer. N Engl J Med. 2023;388(6):489-498. doi:10.1056/NEJMoa2212083
  9. Koike T, Hasebe T, Nakamura M, Shimizu Y, Goto T, Tsuchida M. Towards better outcomes: segmentectomy for ground-glass opacity-dominant non-small cell lung cancer 3 cm or less─insights form JCOG1211 [editorial commentary]. AME Clin Trials Rev. 2023;1:5. doi:10.21037/actr-23-10
  10. Aokage K, Suzuki K, Saji H, et al; for the Japan Clinical Oncology Group. Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including groundglass opacity (JCOG1211): a multicentre, single-arm, confirmatory phase 3 trial. Lancet Respir Med. 2023;11(6):540-549. doi:10.1016/S2213-2600(23)00041-3    
  11. Mandula JK, Sierra-Mondragon RA, Jimenez RV, et al. Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages. Immunity. 2024;57(5):1124-1140.e9. doi:10.1016/j.immuni.2024.03.020

 

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Targeted Therapies and Surgical Resection for Lung Cancer: Evolving Treatment Options
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Lung cancer, the leading cause of cancer-related deaths in the United States, is expected to have 234,580 new cases and 125,070 deaths in 2024.1 Targeted therapies directed toward ROS1, ALK, and RET* have demonstrated clinically significant outcomes for patients with non-small cell lung cancer (NSCLC).2-5 Further emerging novel drug formulations, including macrophage immune checkpoint inhibitors, inhaled cytokines, and Notch ligands,show promise with targeted delivery and fewer adverse effects with in-vitro and murine models.6,7 Lobectomy is currently the gold standard for NSCLC treatment. However, sublobar resection (segmentectomy or wedge) are viable alternatives for early-stage NSCLCs, as shown in the CALGB 140503 and JCOG0802/ WJOG4607L112 trials.8-10 As lung cancer screening with computed tomography increases, detection of early-stage NSCLC, primarily adenocarcinoma, has also grown. Many of these lesions are peripheral and ground-glass opacity-dominant tumors.9 The CALGB 140503 and JCOG0802/JCOG1211 trials suggest sublobar resection is associated with an even lower risk than lobectomy, thus preserving lung function.8-10 The JCOG0802/JCOG1211 trials specifically demonstrate segmentectomy does not compromise therapeutic efficacy for tumors ≤ 3 cm.9,10 Targeted therapies are showing potential for treating NSCLC, and sublobar resection is proving to be a viable alternative to lobectomy for certain NSCLC cases. These developments mark significant strides in lung cancer treatments.

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