Cancer Data Trends 2024: Breast Cancer

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References

1. US Department of Veterans Affairs. Mammogram/breast health. March 28, 2022. Accessed January 10, 2024. https://www.womenshealth.va.gov/topics/mammogram-breast-health.asp

2. First anniversary of Mammography and Medical Options Act (MAMMO Act). VA News. June 6, 2023. Accessed January 10, 2024. https://news.va.gov/120476/anniversary-mammography-and-medicaloptions-act/

3. Moss HA, Rasmussen, KM, Patil, V, et al. Demographic characteristics of veterans diagnosed with breast and gynecologic cancers: a comparative analysis with the general population. Abstract presented at: Annual Meeting of the Association of VA Hematology/ Oncology (AVAHO); September 29–October 1, 2023; Chicago, IL. Abstract 47.

4. US Department of Veterans Affairs. Racial and ethnic minority veterans. Updated July 9, 2020. Accessed January 10, 2024. https:// www.va.gov/HEALTHEQUITY/Race_Ethnicity.asp

5. Stringer-Reasor EM, Elkhanany A, Khoury K, Simon MA, Newman LA. Disparities in breast cancer associated with African American identity. Am Soc Clin Oncol Educ Book. 2021;41:e29-e46. doi:10.1200/EDBK_319929

6. Landry I, Sumbly V, Vest M. Advancements in the treatment of triple- CANCER DATA TRENDS 2024 MARCH 2024 • FEDERAL PRACTITIONER negative breast cancer: a narrative review of the literature. Cureus. 2022;14(2):e21970. doi:10.7759/cureus.21970

7. Schlam I, Tolaney SM, Tarantino P. How I treat HER2-low advanced breast cancer. Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005

8. Modi S, Jacot W, Yamashita T, et al; for the DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690

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George E. Wahlen VA Medical Center
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References

1. US Department of Veterans Affairs. Mammogram/breast health. March 28, 2022. Accessed January 10, 2024. https://www.womenshealth.va.gov/topics/mammogram-breast-health.asp

2. First anniversary of Mammography and Medical Options Act (MAMMO Act). VA News. June 6, 2023. Accessed January 10, 2024. https://news.va.gov/120476/anniversary-mammography-and-medicaloptions-act/

3. Moss HA, Rasmussen, KM, Patil, V, et al. Demographic characteristics of veterans diagnosed with breast and gynecologic cancers: a comparative analysis with the general population. Abstract presented at: Annual Meeting of the Association of VA Hematology/ Oncology (AVAHO); September 29–October 1, 2023; Chicago, IL. Abstract 47.

4. US Department of Veterans Affairs. Racial and ethnic minority veterans. Updated July 9, 2020. Accessed January 10, 2024. https:// www.va.gov/HEALTHEQUITY/Race_Ethnicity.asp

5. Stringer-Reasor EM, Elkhanany A, Khoury K, Simon MA, Newman LA. Disparities in breast cancer associated with African American identity. Am Soc Clin Oncol Educ Book. 2021;41:e29-e46. doi:10.1200/EDBK_319929

6. Landry I, Sumbly V, Vest M. Advancements in the treatment of triple- CANCER DATA TRENDS 2024 MARCH 2024 • FEDERAL PRACTITIONER negative breast cancer: a narrative review of the literature. Cureus. 2022;14(2):e21970. doi:10.7759/cureus.21970

7. Schlam I, Tolaney SM, Tarantino P. How I treat HER2-low advanced breast cancer. Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005

8. Modi S, Jacot W, Yamashita T, et al; for the DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690

References

1. US Department of Veterans Affairs. Mammogram/breast health. March 28, 2022. Accessed January 10, 2024. https://www.womenshealth.va.gov/topics/mammogram-breast-health.asp

2. First anniversary of Mammography and Medical Options Act (MAMMO Act). VA News. June 6, 2023. Accessed January 10, 2024. https://news.va.gov/120476/anniversary-mammography-and-medicaloptions-act/

3. Moss HA, Rasmussen, KM, Patil, V, et al. Demographic characteristics of veterans diagnosed with breast and gynecologic cancers: a comparative analysis with the general population. Abstract presented at: Annual Meeting of the Association of VA Hematology/ Oncology (AVAHO); September 29–October 1, 2023; Chicago, IL. Abstract 47.

4. US Department of Veterans Affairs. Racial and ethnic minority veterans. Updated July 9, 2020. Accessed January 10, 2024. https:// www.va.gov/HEALTHEQUITY/Race_Ethnicity.asp

5. Stringer-Reasor EM, Elkhanany A, Khoury K, Simon MA, Newman LA. Disparities in breast cancer associated with African American identity. Am Soc Clin Oncol Educ Book. 2021;41:e29-e46. doi:10.1200/EDBK_319929

6. Landry I, Sumbly V, Vest M. Advancements in the treatment of triple- CANCER DATA TRENDS 2024 MARCH 2024 • FEDERAL PRACTITIONER negative breast cancer: a narrative review of the literature. Cureus. 2022;14(2):e21970. doi:10.7759/cureus.21970

7. Schlam I, Tolaney SM, Tarantino P. How I treat HER2-low advanced breast cancer. Breast. 2023;67:116-123. doi:10.1016/j.breast.2023.01.005

8. Modi S, Jacot W, Yamashita T, et al; for the DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690

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Cancer Data Trends 2024: Colorectal Cancer

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Cancer Data Trends 2024: Colorectal Cancer
References

1. May FP, Yano EM, Provenzale D, et al. Barriers to follow-up colonoscopies for patients with positive results from fecal immunochemical tests during colorectal cancer screening. Clin Gastroenterol Hepatol. 2019;17(3):469-476. doi:10.1016/j.cgh.2018.05.022

2. San Miguel Y, Demb J, Martinez ME, Gupta S, May FP. Time to colonoscopy after abnormal stool-based screening and risk for colorectal cancer incidence and mortality. Gastroenterology. 2021;160(6):1997-2005.e3. doi:10.1053/j.gastro.2021.01.219

3. Coronado GD, Rawlings AM, Petrik AF, et al. Precision patient navigation to improve rates of follow-up colonoscopy, an individual randomized effectiveness trial. Cancer Epidemiol Biomarkers Prev. 2021;30(12):2327-2333. doi:10.1158/1055-9965.EPI-20-1793

4. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget stool RNA test for colorectal cancer screening. JAMA. 2023;330(18):1760- 1768. doi:10.1001/jama.2023.22231

5. McNamara D. Two multitarget stool tests show promise for CRC screening: studies. Medscape. Published October 22, 2023. Accessed December 20, 2023. https://www.medscape.com/viewarticle/997609#vp_1

6. Clinical validation of an optimized multi-target stool DNA (Mt-sDNA 2.0) test, for colorectal cancer screening “BLUE-C.” ClinicalTrials. gov identifier: NCT04144738. Updated September 1, 2023. Accessed December 20, 2023. https://www.clinicaltrials.gov/study/ NCT04144738

7. Universal Diagnostics. Universal DX Presents Data from Large, 1,000-patient, Multi-Cohort Study Proving 93% Sensitivity for Colorectal Cancer and 54% Sensitivity for Advanced Adenoma at 92% Specificity. Press Release. Published May 2023. Accessed January 26. 2024.

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Divya Bhatt, MD, has disclosed the following relevant financial relationship:
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VA North Texas Health Care System
Dallas, TX

Divya Bhatt, MD, has disclosed the following relevant financial relationship:
Received research grant from: VA North Texas Health Care System 2019-2021

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University of Texas Southwestern
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VA North Texas Health Care System
Dallas, TX

Divya Bhatt, MD, has disclosed the following relevant financial relationship:
Received research grant from: VA North Texas Health Care System 2019-2021

References

1. May FP, Yano EM, Provenzale D, et al. Barriers to follow-up colonoscopies for patients with positive results from fecal immunochemical tests during colorectal cancer screening. Clin Gastroenterol Hepatol. 2019;17(3):469-476. doi:10.1016/j.cgh.2018.05.022

2. San Miguel Y, Demb J, Martinez ME, Gupta S, May FP. Time to colonoscopy after abnormal stool-based screening and risk for colorectal cancer incidence and mortality. Gastroenterology. 2021;160(6):1997-2005.e3. doi:10.1053/j.gastro.2021.01.219

3. Coronado GD, Rawlings AM, Petrik AF, et al. Precision patient navigation to improve rates of follow-up colonoscopy, an individual randomized effectiveness trial. Cancer Epidemiol Biomarkers Prev. 2021;30(12):2327-2333. doi:10.1158/1055-9965.EPI-20-1793

4. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget stool RNA test for colorectal cancer screening. JAMA. 2023;330(18):1760- 1768. doi:10.1001/jama.2023.22231

5. McNamara D. Two multitarget stool tests show promise for CRC screening: studies. Medscape. Published October 22, 2023. Accessed December 20, 2023. https://www.medscape.com/viewarticle/997609#vp_1

6. Clinical validation of an optimized multi-target stool DNA (Mt-sDNA 2.0) test, for colorectal cancer screening “BLUE-C.” ClinicalTrials. gov identifier: NCT04144738. Updated September 1, 2023. Accessed December 20, 2023. https://www.clinicaltrials.gov/study/ NCT04144738

7. Universal Diagnostics. Universal DX Presents Data from Large, 1,000-patient, Multi-Cohort Study Proving 93% Sensitivity for Colorectal Cancer and 54% Sensitivity for Advanced Adenoma at 92% Specificity. Press Release. Published May 2023. Accessed January 26. 2024.

References

1. May FP, Yano EM, Provenzale D, et al. Barriers to follow-up colonoscopies for patients with positive results from fecal immunochemical tests during colorectal cancer screening. Clin Gastroenterol Hepatol. 2019;17(3):469-476. doi:10.1016/j.cgh.2018.05.022

2. San Miguel Y, Demb J, Martinez ME, Gupta S, May FP. Time to colonoscopy after abnormal stool-based screening and risk for colorectal cancer incidence and mortality. Gastroenterology. 2021;160(6):1997-2005.e3. doi:10.1053/j.gastro.2021.01.219

3. Coronado GD, Rawlings AM, Petrik AF, et al. Precision patient navigation to improve rates of follow-up colonoscopy, an individual randomized effectiveness trial. Cancer Epidemiol Biomarkers Prev. 2021;30(12):2327-2333. doi:10.1158/1055-9965.EPI-20-1793

4. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget stool RNA test for colorectal cancer screening. JAMA. 2023;330(18):1760- 1768. doi:10.1001/jama.2023.22231

5. McNamara D. Two multitarget stool tests show promise for CRC screening: studies. Medscape. Published October 22, 2023. Accessed December 20, 2023. https://www.medscape.com/viewarticle/997609#vp_1

6. Clinical validation of an optimized multi-target stool DNA (Mt-sDNA 2.0) test, for colorectal cancer screening “BLUE-C.” ClinicalTrials. gov identifier: NCT04144738. Updated September 1, 2023. Accessed December 20, 2023. https://www.clinicaltrials.gov/study/ NCT04144738

7. Universal Diagnostics. Universal DX Presents Data from Large, 1,000-patient, Multi-Cohort Study Proving 93% Sensitivity for Colorectal Cancer and 54% Sensitivity for Advanced Adenoma at 92% Specificity. Press Release. Published May 2023. Accessed January 26. 2024.

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Cancer Data Trends 2024: Lung Cancer

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Cancer Data Trends 2024: Lung Cancer
References

1. Wolf AMD, Oeffinger KC, Shih TYC, et al. Screening for lung cancer: 2023 guideline update from the American Cancer Society. CA Cancer J Clin. 2023;10.3322/caac.21811. doi:10.3322/caac.21811

2. US Department of Veterans Affairs. VA promotes high-quality, patient-centered lung cancer screening for veterans. Published June 15, 2023. Accessed December 18, 2023. http://www.hsrd.research.va.gov/impacts/lcs.cfm

3. Navuluri N, Morrison S, Green CL, et al. Racial disparities in lung cancer screening among veterans, 2013 to 2021. JAMA Netw Open. 2023;6(6):e2318795. doi:10.1001/jamanetworkopen.2023.18795

4. Bruno DS, Hess LM, Li X, Su EW, Patel M. Disparities in biomarker testing and clinical trial enrollment among patients with lung, breast, or colorectal cancers in the United States. JCO Precis Oncol. 2022;6:e2100427. doi:10.1200/PO.21.00427

5. Jalal SI, Guo A, Ahmed S, Kelley MJ. Analysis of actionable genetic alterations in lung carcinoma from the VA National Precision Oncology Program. Semin Oncol. 2022;S0093-7754(22)00054-9. doi:10.1053/j.seminoncol.2022.06.014

6. Williams CD, Allo MA, Gu L, Vashistha V, Press A, Kelley M. Health outcomes and healthcare resource utilization among veterans with stage IV non-small cell lung cancer treated with second-line chemotherapy versus immunotherapy. PLoS One. 2023;18(2):e0282020. doi:10.1371/journal.pone.0282020

7. US Food and Drug Administration. Oncology (cancer)/hematologic malignancies approval notifications. Updated December 15, 2023. Accessed December 18, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications

8. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. doi:10.1016/j.esmoop.2022.100408

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University of Nebraska Medical Center
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VA Nebraska-Western Iowa Health Care System
Omaha, NE

Apar Kishor Ganti, MD, MS, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Flagship Biosciences; G1 Therapeutics; Jazz Pharmaceuticals; Cardinal Health; Mirati Therapeutics; Regeneron Pharmaceuticals; Sanofi; Genzyme; Eisai

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Professor, Department of Medicine
University of Nebraska Medical Center
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VA Nebraska-Western Iowa Health Care System
Omaha, NE

Apar Kishor Ganti, MD, MS, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Flagship Biosciences; G1 Therapeutics; Jazz Pharmaceuticals; Cardinal Health; Mirati Therapeutics; Regeneron Pharmaceuticals; Sanofi; Genzyme; Eisai

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Reviewed by Apar Kishor Ganti, MD, MS
Professor, Department of Medicine
University of Nebraska Medical Center
Staff Physician, Department of Internal Medicine
VA Nebraska-Western Iowa Health Care System
Omaha, NE

Apar Kishor Ganti, MD, MS, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Flagship Biosciences; G1 Therapeutics; Jazz Pharmaceuticals; Cardinal Health; Mirati Therapeutics; Regeneron Pharmaceuticals; Sanofi; Genzyme; Eisai

References

1. Wolf AMD, Oeffinger KC, Shih TYC, et al. Screening for lung cancer: 2023 guideline update from the American Cancer Society. CA Cancer J Clin. 2023;10.3322/caac.21811. doi:10.3322/caac.21811

2. US Department of Veterans Affairs. VA promotes high-quality, patient-centered lung cancer screening for veterans. Published June 15, 2023. Accessed December 18, 2023. http://www.hsrd.research.va.gov/impacts/lcs.cfm

3. Navuluri N, Morrison S, Green CL, et al. Racial disparities in lung cancer screening among veterans, 2013 to 2021. JAMA Netw Open. 2023;6(6):e2318795. doi:10.1001/jamanetworkopen.2023.18795

4. Bruno DS, Hess LM, Li X, Su EW, Patel M. Disparities in biomarker testing and clinical trial enrollment among patients with lung, breast, or colorectal cancers in the United States. JCO Precis Oncol. 2022;6:e2100427. doi:10.1200/PO.21.00427

5. Jalal SI, Guo A, Ahmed S, Kelley MJ. Analysis of actionable genetic alterations in lung carcinoma from the VA National Precision Oncology Program. Semin Oncol. 2022;S0093-7754(22)00054-9. doi:10.1053/j.seminoncol.2022.06.014

6. Williams CD, Allo MA, Gu L, Vashistha V, Press A, Kelley M. Health outcomes and healthcare resource utilization among veterans with stage IV non-small cell lung cancer treated with second-line chemotherapy versus immunotherapy. PLoS One. 2023;18(2):e0282020. doi:10.1371/journal.pone.0282020

7. US Food and Drug Administration. Oncology (cancer)/hematologic malignancies approval notifications. Updated December 15, 2023. Accessed December 18, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications

8. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. doi:10.1016/j.esmoop.2022.100408

References

1. Wolf AMD, Oeffinger KC, Shih TYC, et al. Screening for lung cancer: 2023 guideline update from the American Cancer Society. CA Cancer J Clin. 2023;10.3322/caac.21811. doi:10.3322/caac.21811

2. US Department of Veterans Affairs. VA promotes high-quality, patient-centered lung cancer screening for veterans. Published June 15, 2023. Accessed December 18, 2023. http://www.hsrd.research.va.gov/impacts/lcs.cfm

3. Navuluri N, Morrison S, Green CL, et al. Racial disparities in lung cancer screening among veterans, 2013 to 2021. JAMA Netw Open. 2023;6(6):e2318795. doi:10.1001/jamanetworkopen.2023.18795

4. Bruno DS, Hess LM, Li X, Su EW, Patel M. Disparities in biomarker testing and clinical trial enrollment among patients with lung, breast, or colorectal cancers in the United States. JCO Precis Oncol. 2022;6:e2100427. doi:10.1200/PO.21.00427

5. Jalal SI, Guo A, Ahmed S, Kelley MJ. Analysis of actionable genetic alterations in lung carcinoma from the VA National Precision Oncology Program. Semin Oncol. 2022;S0093-7754(22)00054-9. doi:10.1053/j.seminoncol.2022.06.014

6. Williams CD, Allo MA, Gu L, Vashistha V, Press A, Kelley M. Health outcomes and healthcare resource utilization among veterans with stage IV non-small cell lung cancer treated with second-line chemotherapy versus immunotherapy. PLoS One. 2023;18(2):e0282020. doi:10.1371/journal.pone.0282020

7. US Food and Drug Administration. Oncology (cancer)/hematologic malignancies approval notifications. Updated December 15, 2023. Accessed December 18, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications

8. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. doi:10.1016/j.esmoop.2022.100408

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Cancer Data Trends 2024: Multiple Myeloma

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Cancer Data Trends 2024: Multiple Myeloma
References

1. Mahmood S, Gupta P, Ma H. Impact of time period of diagnosis, race, and military exposures on the survival of US military veterans with multiple myeloma and/or plasmacytoma. J Clin Oncol. 2023;41(16 suppl). Abstract e20061. https://doi.org/10.1200/jco.2023.41.16_suppl.e20061  

2. National Cancer Institute. Cancer stat facts: myeloma. Accessed January 2, 2024. https://seer.cancer.gov/statfacts/html/mulmy.html 

3. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2022;33(1):117]. Ann Oncol. 2021;32(3):309-322. doi: 10.1016/j.annonc.2020.11.014 

4. Su CT, Chen JC, Sussman JB. Virtual care for multiple myeloma in the COVID-19 era: interrupted time series analysis of Veterans Health Administration data. Leuk Lymphoma. 2023;64(5):1035-1039. doi: 10.1080/10428194.2023.2189989 

5. O’Donnell EK, Shapiro YN, Yee AJ, et al. Quality of life, psychological distress, and prognostic perceptions in patients with multiple myeloma. Cancer. 2022;128(10):1996-2004. doi: 10.1002/cncr.34134 

6. O’Donnell EK, Shapiro YN, Yee AJ, et al. Quality of life, psychological distress, and prognostic perceptions in caregivers of patients with multiple myeloma. Blood Adv. 2022;6(17):4967-4974. doi: 10.1182/bloodadvances.2022007127 

7. Ahmed N, Shahzad M, Shippey E, et al. Socioeconomic and racial disparity in chimeric antigen receptor T cell therapy access. Transplant Cell Ther. 2022;28(7):358-364. doi: 10.1016/j.jtct.2022.04.008 

 

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University of Washington
Fred Hutchinson Cancer Center
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Dr. Su has no relevant financial relationships to disclose.

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Fred Hutchinson Cancer Center
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Reviewed by Christopher Su, MD, MPH
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University of Washington
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Dr. Su has no relevant financial relationships to disclose.

References

1. Mahmood S, Gupta P, Ma H. Impact of time period of diagnosis, race, and military exposures on the survival of US military veterans with multiple myeloma and/or plasmacytoma. J Clin Oncol. 2023;41(16 suppl). Abstract e20061. https://doi.org/10.1200/jco.2023.41.16_suppl.e20061  

2. National Cancer Institute. Cancer stat facts: myeloma. Accessed January 2, 2024. https://seer.cancer.gov/statfacts/html/mulmy.html 

3. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2022;33(1):117]. Ann Oncol. 2021;32(3):309-322. doi: 10.1016/j.annonc.2020.11.014 

4. Su CT, Chen JC, Sussman JB. Virtual care for multiple myeloma in the COVID-19 era: interrupted time series analysis of Veterans Health Administration data. Leuk Lymphoma. 2023;64(5):1035-1039. doi: 10.1080/10428194.2023.2189989 

5. O’Donnell EK, Shapiro YN, Yee AJ, et al. Quality of life, psychological distress, and prognostic perceptions in patients with multiple myeloma. Cancer. 2022;128(10):1996-2004. doi: 10.1002/cncr.34134 

6. O’Donnell EK, Shapiro YN, Yee AJ, et al. Quality of life, psychological distress, and prognostic perceptions in caregivers of patients with multiple myeloma. Blood Adv. 2022;6(17):4967-4974. doi: 10.1182/bloodadvances.2022007127 

7. Ahmed N, Shahzad M, Shippey E, et al. Socioeconomic and racial disparity in chimeric antigen receptor T cell therapy access. Transplant Cell Ther. 2022;28(7):358-364. doi: 10.1016/j.jtct.2022.04.008 

 

References

1. Mahmood S, Gupta P, Ma H. Impact of time period of diagnosis, race, and military exposures on the survival of US military veterans with multiple myeloma and/or plasmacytoma. J Clin Oncol. 2023;41(16 suppl). Abstract e20061. https://doi.org/10.1200/jco.2023.41.16_suppl.e20061  

2. National Cancer Institute. Cancer stat facts: myeloma. Accessed January 2, 2024. https://seer.cancer.gov/statfacts/html/mulmy.html 

3. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2022;33(1):117]. Ann Oncol. 2021;32(3):309-322. doi: 10.1016/j.annonc.2020.11.014 

4. Su CT, Chen JC, Sussman JB. Virtual care for multiple myeloma in the COVID-19 era: interrupted time series analysis of Veterans Health Administration data. Leuk Lymphoma. 2023;64(5):1035-1039. doi: 10.1080/10428194.2023.2189989 

5. O’Donnell EK, Shapiro YN, Yee AJ, et al. Quality of life, psychological distress, and prognostic perceptions in patients with multiple myeloma. Cancer. 2022;128(10):1996-2004. doi: 10.1002/cncr.34134 

6. O’Donnell EK, Shapiro YN, Yee AJ, et al. Quality of life, psychological distress, and prognostic perceptions in caregivers of patients with multiple myeloma. Blood Adv. 2022;6(17):4967-4974. doi: 10.1182/bloodadvances.2022007127 

7. Ahmed N, Shahzad M, Shippey E, et al. Socioeconomic and racial disparity in chimeric antigen receptor T cell therapy access. Transplant Cell Ther. 2022;28(7):358-364. doi: 10.1016/j.jtct.2022.04.008 

 

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References

1. Pinheiro PS, Jones PD, Medina H, et al. Incidence of etiology-specific hepatocellular carcinoma: diIverging trends and significant heterogeneity by race and ethnicity. Clin Gastroenterol Hepatol. Published online September 6, 2023. doi:10.1016/j.cgh.2023.08.016
 

2. Ju MR, Karalis JD, Chansard M, et al. Variation of hepatocellular carcinoma treatment patterns and survival across geographic regions in a veteran population. Ann Surg Oncol. 2022;29(13):8413-8420. doi:10.1245/s10434-022-12390-7
 

3. Veterans Health Administration. VA collaborative consensus on a pathway for the development of a multidisciplinary team to manage hepatocellular carcinoma. VA Liver Cancer Summit; March 8, 2019; Miami, FL. Accessed December 14, 2023. https://www.hepatitis.va.gov/pdf/HCC-multidisciplinary-management-best-practices.pdf
 

4. Emerson L. Hepatocellular carcinoma treatment, survival varies among VA regions. US Medicine. Published June 12, 2023. Accessed December 14, 2023. https://www.usmedicine.com/clinical-topics/cancer/hepatocellular-carcinoma/hepatocellular-carcinoma-treatment-survival-varies-among-va-regions/
 

5. Agarwal PD, Haftoglou BA, Ziemlewicz TJ, Lucey MR, Said A. Psychosocial barriers and their impact on hepatocellular carcinoma care in US veterans: tumor board model of care. Fed Pract. 2022;39(suppl 2):S32-S36. doi:10.12788/fp.0272
 

6. Ito T, Nguyen MH. Perspectives on the underlying etiology of HCC and its effects on treatment outcomes. J Hepatocell Carcinoma. 2023;10:413-428. doi:10.2147/JHC.S347959
 

7. Garren P, Serper M. Chronic hepatitis B in US veterans. Curr Hepatol Rep. 2019;18(3):310-315. doi:10.1007/s11901-019-00479-9
 

8. US Department of Veteran Affairs. Hepatitis C: information for veterans. Published November 2022. Accessed December 14, 2023. https://www.hepatitis.va.gov/pdf/Hepatitis-C-Factsheet-Veterans.pdf

9. Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci. 2015;3(4):732-736. doi:10.3889/oamjms.2015.111
 

10. Elderkin J, Al Hallak N, Azmi AS, et al. Hepatocellular carcinoma: surveillance, diagnosis, evaluation and management. Cancers (Basel). 2023;15(21):5118. doi:http://doi.org/10.3390/cancers15215118
 

11. Wei H, Yang J, Lu R, et al. m6A modification of AC026356.1 facilitates hepatocellular carcinoma progression by regulating the IGF2BP1-IL11 axis. Sci Rep. 2023;13(1):19124. doi:10.1038/s41598-023-45449-w
 

12. Espinoza M, Muquith M, Lim M, Zhu H, Singal AG, Hsiehchen D. Disease etiology and outcomes after atezolizumab plus bevacizumab in hepatocellular carcinoma: post-hoc analysis of IMbrave150. Gastroenterology. 2023;165(1):286-288.e4. doi:10.1053/j.gastro.2023.02.042
 

13. Zhang H, Zhang W, Jiang L, Chen Y. Recent advances in systemic therapy for hepatocellular carcinoma. Biomark Res. 2022;10(1):3. doi:10.1186/s40364-021-00350-4
 

14. Johnson P, Zhou Q, Dao DY, Lo YMD. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2022;19(10):670-681. doi:10.1038/s41575-022-00620-y
 

15. US Department of Veteran Affairs. VA Cooperative Studies Program (CSP). CSP #2023 PREventing liver cancer Mortality through Imaging with Ultrasound vs MRI (PREMIUM STUDY). Updated July 2022. Accessed December 14, 2023. https://www.vacsp.research.va.gov /CSP_2023/CSP_2023.asp

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Dr. Moylan has no relevant financial relationships to disclose.

References

1. Pinheiro PS, Jones PD, Medina H, et al. Incidence of etiology-specific hepatocellular carcinoma: diIverging trends and significant heterogeneity by race and ethnicity. Clin Gastroenterol Hepatol. Published online September 6, 2023. doi:10.1016/j.cgh.2023.08.016
 

2. Ju MR, Karalis JD, Chansard M, et al. Variation of hepatocellular carcinoma treatment patterns and survival across geographic regions in a veteran population. Ann Surg Oncol. 2022;29(13):8413-8420. doi:10.1245/s10434-022-12390-7
 

3. Veterans Health Administration. VA collaborative consensus on a pathway for the development of a multidisciplinary team to manage hepatocellular carcinoma. VA Liver Cancer Summit; March 8, 2019; Miami, FL. Accessed December 14, 2023. https://www.hepatitis.va.gov/pdf/HCC-multidisciplinary-management-best-practices.pdf
 

4. Emerson L. Hepatocellular carcinoma treatment, survival varies among VA regions. US Medicine. Published June 12, 2023. Accessed December 14, 2023. https://www.usmedicine.com/clinical-topics/cancer/hepatocellular-carcinoma/hepatocellular-carcinoma-treatment-survival-varies-among-va-regions/
 

5. Agarwal PD, Haftoglou BA, Ziemlewicz TJ, Lucey MR, Said A. Psychosocial barriers and their impact on hepatocellular carcinoma care in US veterans: tumor board model of care. Fed Pract. 2022;39(suppl 2):S32-S36. doi:10.12788/fp.0272
 

6. Ito T, Nguyen MH. Perspectives on the underlying etiology of HCC and its effects on treatment outcomes. J Hepatocell Carcinoma. 2023;10:413-428. doi:10.2147/JHC.S347959
 

7. Garren P, Serper M. Chronic hepatitis B in US veterans. Curr Hepatol Rep. 2019;18(3):310-315. doi:10.1007/s11901-019-00479-9
 

8. US Department of Veteran Affairs. Hepatitis C: information for veterans. Published November 2022. Accessed December 14, 2023. https://www.hepatitis.va.gov/pdf/Hepatitis-C-Factsheet-Veterans.pdf

9. Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci. 2015;3(4):732-736. doi:10.3889/oamjms.2015.111
 

10. Elderkin J, Al Hallak N, Azmi AS, et al. Hepatocellular carcinoma: surveillance, diagnosis, evaluation and management. Cancers (Basel). 2023;15(21):5118. doi:http://doi.org/10.3390/cancers15215118
 

11. Wei H, Yang J, Lu R, et al. m6A modification of AC026356.1 facilitates hepatocellular carcinoma progression by regulating the IGF2BP1-IL11 axis. Sci Rep. 2023;13(1):19124. doi:10.1038/s41598-023-45449-w
 

12. Espinoza M, Muquith M, Lim M, Zhu H, Singal AG, Hsiehchen D. Disease etiology and outcomes after atezolizumab plus bevacizumab in hepatocellular carcinoma: post-hoc analysis of IMbrave150. Gastroenterology. 2023;165(1):286-288.e4. doi:10.1053/j.gastro.2023.02.042
 

13. Zhang H, Zhang W, Jiang L, Chen Y. Recent advances in systemic therapy for hepatocellular carcinoma. Biomark Res. 2022;10(1):3. doi:10.1186/s40364-021-00350-4
 

14. Johnson P, Zhou Q, Dao DY, Lo YMD. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2022;19(10):670-681. doi:10.1038/s41575-022-00620-y
 

15. US Department of Veteran Affairs. VA Cooperative Studies Program (CSP). CSP #2023 PREventing liver cancer Mortality through Imaging with Ultrasound vs MRI (PREMIUM STUDY). Updated July 2022. Accessed December 14, 2023. https://www.vacsp.research.va.gov /CSP_2023/CSP_2023.asp

References

1. Pinheiro PS, Jones PD, Medina H, et al. Incidence of etiology-specific hepatocellular carcinoma: diIverging trends and significant heterogeneity by race and ethnicity. Clin Gastroenterol Hepatol. Published online September 6, 2023. doi:10.1016/j.cgh.2023.08.016
 

2. Ju MR, Karalis JD, Chansard M, et al. Variation of hepatocellular carcinoma treatment patterns and survival across geographic regions in a veteran population. Ann Surg Oncol. 2022;29(13):8413-8420. doi:10.1245/s10434-022-12390-7
 

3. Veterans Health Administration. VA collaborative consensus on a pathway for the development of a multidisciplinary team to manage hepatocellular carcinoma. VA Liver Cancer Summit; March 8, 2019; Miami, FL. Accessed December 14, 2023. https://www.hepatitis.va.gov/pdf/HCC-multidisciplinary-management-best-practices.pdf
 

4. Emerson L. Hepatocellular carcinoma treatment, survival varies among VA regions. US Medicine. Published June 12, 2023. Accessed December 14, 2023. https://www.usmedicine.com/clinical-topics/cancer/hepatocellular-carcinoma/hepatocellular-carcinoma-treatment-survival-varies-among-va-regions/
 

5. Agarwal PD, Haftoglou BA, Ziemlewicz TJ, Lucey MR, Said A. Psychosocial barriers and their impact on hepatocellular carcinoma care in US veterans: tumor board model of care. Fed Pract. 2022;39(suppl 2):S32-S36. doi:10.12788/fp.0272
 

6. Ito T, Nguyen MH. Perspectives on the underlying etiology of HCC and its effects on treatment outcomes. J Hepatocell Carcinoma. 2023;10:413-428. doi:10.2147/JHC.S347959
 

7. Garren P, Serper M. Chronic hepatitis B in US veterans. Curr Hepatol Rep. 2019;18(3):310-315. doi:10.1007/s11901-019-00479-9
 

8. US Department of Veteran Affairs. Hepatitis C: information for veterans. Published November 2022. Accessed December 14, 2023. https://www.hepatitis.va.gov/pdf/Hepatitis-C-Factsheet-Veterans.pdf

9. Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci. 2015;3(4):732-736. doi:10.3889/oamjms.2015.111
 

10. Elderkin J, Al Hallak N, Azmi AS, et al. Hepatocellular carcinoma: surveillance, diagnosis, evaluation and management. Cancers (Basel). 2023;15(21):5118. doi:http://doi.org/10.3390/cancers15215118
 

11. Wei H, Yang J, Lu R, et al. m6A modification of AC026356.1 facilitates hepatocellular carcinoma progression by regulating the IGF2BP1-IL11 axis. Sci Rep. 2023;13(1):19124. doi:10.1038/s41598-023-45449-w
 

12. Espinoza M, Muquith M, Lim M, Zhu H, Singal AG, Hsiehchen D. Disease etiology and outcomes after atezolizumab plus bevacizumab in hepatocellular carcinoma: post-hoc analysis of IMbrave150. Gastroenterology. 2023;165(1):286-288.e4. doi:10.1053/j.gastro.2023.02.042
 

13. Zhang H, Zhang W, Jiang L, Chen Y. Recent advances in systemic therapy for hepatocellular carcinoma. Biomark Res. 2022;10(1):3. doi:10.1186/s40364-021-00350-4
 

14. Johnson P, Zhou Q, Dao DY, Lo YMD. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2022;19(10):670-681. doi:10.1038/s41575-022-00620-y
 

15. US Department of Veteran Affairs. VA Cooperative Studies Program (CSP). CSP #2023 PREventing liver cancer Mortality through Imaging with Ultrasound vs MRI (PREMIUM STUDY). Updated July 2022. Accessed December 14, 2023. https://www.vacsp.research.va.gov /CSP_2023/CSP_2023.asp

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Cancer Data Trends 2024

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Cancer Data Trends 2024

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

Click to view the Digital Edition.

 

 

In this issue: 

Hepatocellular Carcinoma
Special care for veterans, changes in staging, and biomarkers for early diagnosis

Lung Cancer
Guideline updates and racial disparities in veterans

Multiple Myeloma
Improving survival in the VA

Colorectal Cancer
Barriers to follow-up colonoscopies after FIT testing 

B-Cell Lymphomas
Findings from the VA's National TeleOncology Program and recent therapy updates

Breast Cancer
A look at the VA's Risk Assessment Pipeline and incidence among veterans vs the general population

Genitourinary Cancers
Molecular testing in prostate cancer, improving survival for metastatic RCC, and links between bladder cancer and Agent Orange exposure

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The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

Click to view the Digital Edition.

 

 

In this issue: 

Hepatocellular Carcinoma
Special care for veterans, changes in staging, and biomarkers for early diagnosis

Lung Cancer
Guideline updates and racial disparities in veterans

Multiple Myeloma
Improving survival in the VA

Colorectal Cancer
Barriers to follow-up colonoscopies after FIT testing 

B-Cell Lymphomas
Findings from the VA's National TeleOncology Program and recent therapy updates

Breast Cancer
A look at the VA's Risk Assessment Pipeline and incidence among veterans vs the general population

Genitourinary Cancers
Molecular testing in prostate cancer, improving survival for metastatic RCC, and links between bladder cancer and Agent Orange exposure

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

Click to view the Digital Edition.

 

 

In this issue: 

Hepatocellular Carcinoma
Special care for veterans, changes in staging, and biomarkers for early diagnosis

Lung Cancer
Guideline updates and racial disparities in veterans

Multiple Myeloma
Improving survival in the VA

Colorectal Cancer
Barriers to follow-up colonoscopies after FIT testing 

B-Cell Lymphomas
Findings from the VA's National TeleOncology Program and recent therapy updates

Breast Cancer
A look at the VA's Risk Assessment Pipeline and incidence among veterans vs the general population

Genitourinary Cancers
Molecular testing in prostate cancer, improving survival for metastatic RCC, and links between bladder cancer and Agent Orange exposure

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Cancer Data Trends 2024: Genitourinary Cancers

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References

1. Sokolova A, Cheng H. Germline testing in prostate cancer: when and who to test. Oncology (Williston Park). 2021;35(10):645-653. doi:10.46883/ONC.2021.3510.0645  

2. Tuffaha H, Edmunds K, Fairbairn D, et al. Guidelines for genetic testing in prostate cancer: a scoping review. Prostate Cancer Prostatic Dis. 2023 May 18. doi:10.1038/s41391-023-00676-0 

3.    National Comprehensive Cancer Network. NCCN clinical practice guidelines for prostate cancer. Version 4.2023. September 7, 2023. Accessed December 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf 

4. National Precision Oncology Program. PMID 26149669 (e-mail, December 13, 2023). 

5. Shevach J, Lynch J, Candelieri-Surette D, et al. Racial disparities in germline testing among men with pancreas, breast and metastatic prostate cancers in two health systems. J Clin Oncol. 2023;41(16 suppl):abstract 10549. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.10549  

6. Velaer K, Thomas IC, Yang J, et al. Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: a laboratory wide association study (LWAS). Urol Oncol. 2022;40(1):12.e23-12.e30. doi:10.1016/j.urolonc.2021.08.011 

7. Heng DYC, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013;14(2):141-148. doi:10.1016/S1470-2045(12)70559-4 

8. Aguilar Palacios D, Wilson B, Michael P, et al. A novel metric for hospital quality in kidney cancer surgery: a Veterans Affairs National Health System validation of concept. Urol Pract. 2022;9(3):237-245. doi:10.1097/UPJ.0000000000000294 

9. Williams SB, Janes JL, Howard LE, et al. Exposure to Agent Orange and risk of bladder cancer among US veterans. JAMA Netw Open. 2023;6(6):e2320593. doi:10.1001/jamanetworkopen.2023.20593 

10. Penn T, Borza T, Liou JI, et al. Impact of Agent Orange exposure on non-muscle invasive bladder cancer outcomes. Urology. 2023;182:175-180. doi:10.1016/j.urology.2023.08.037 

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Reviewed by Bruce Montgomery, MD
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Attending Physician
Department of Medicine, Oncology
University of Washington
Fred Hutchinson Cancer Center
VA Puget Sound Health Care System
Seattle, WA

Dr. Montgomery has no relevant financial relationships to disclose.

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Dr. Montgomery has no relevant financial relationships to disclose.

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Attending Physician
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Dr. Montgomery has no relevant financial relationships to disclose.

References

1. Sokolova A, Cheng H. Germline testing in prostate cancer: when and who to test. Oncology (Williston Park). 2021;35(10):645-653. doi:10.46883/ONC.2021.3510.0645  

2. Tuffaha H, Edmunds K, Fairbairn D, et al. Guidelines for genetic testing in prostate cancer: a scoping review. Prostate Cancer Prostatic Dis. 2023 May 18. doi:10.1038/s41391-023-00676-0 

3.    National Comprehensive Cancer Network. NCCN clinical practice guidelines for prostate cancer. Version 4.2023. September 7, 2023. Accessed December 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf 

4. National Precision Oncology Program. PMID 26149669 (e-mail, December 13, 2023). 

5. Shevach J, Lynch J, Candelieri-Surette D, et al. Racial disparities in germline testing among men with pancreas, breast and metastatic prostate cancers in two health systems. J Clin Oncol. 2023;41(16 suppl):abstract 10549. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.10549  

6. Velaer K, Thomas IC, Yang J, et al. Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: a laboratory wide association study (LWAS). Urol Oncol. 2022;40(1):12.e23-12.e30. doi:10.1016/j.urolonc.2021.08.011 

7. Heng DYC, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013;14(2):141-148. doi:10.1016/S1470-2045(12)70559-4 

8. Aguilar Palacios D, Wilson B, Michael P, et al. A novel metric for hospital quality in kidney cancer surgery: a Veterans Affairs National Health System validation of concept. Urol Pract. 2022;9(3):237-245. doi:10.1097/UPJ.0000000000000294 

9. Williams SB, Janes JL, Howard LE, et al. Exposure to Agent Orange and risk of bladder cancer among US veterans. JAMA Netw Open. 2023;6(6):e2320593. doi:10.1001/jamanetworkopen.2023.20593 

10. Penn T, Borza T, Liou JI, et al. Impact of Agent Orange exposure on non-muscle invasive bladder cancer outcomes. Urology. 2023;182:175-180. doi:10.1016/j.urology.2023.08.037 

References

1. Sokolova A, Cheng H. Germline testing in prostate cancer: when and who to test. Oncology (Williston Park). 2021;35(10):645-653. doi:10.46883/ONC.2021.3510.0645  

2. Tuffaha H, Edmunds K, Fairbairn D, et al. Guidelines for genetic testing in prostate cancer: a scoping review. Prostate Cancer Prostatic Dis. 2023 May 18. doi:10.1038/s41391-023-00676-0 

3.    National Comprehensive Cancer Network. NCCN clinical practice guidelines for prostate cancer. Version 4.2023. September 7, 2023. Accessed December 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf 

4. National Precision Oncology Program. PMID 26149669 (e-mail, December 13, 2023). 

5. Shevach J, Lynch J, Candelieri-Surette D, et al. Racial disparities in germline testing among men with pancreas, breast and metastatic prostate cancers in two health systems. J Clin Oncol. 2023;41(16 suppl):abstract 10549. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.10549  

6. Velaer K, Thomas IC, Yang J, et al. Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: a laboratory wide association study (LWAS). Urol Oncol. 2022;40(1):12.e23-12.e30. doi:10.1016/j.urolonc.2021.08.011 

7. Heng DYC, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013;14(2):141-148. doi:10.1016/S1470-2045(12)70559-4 

8. Aguilar Palacios D, Wilson B, Michael P, et al. A novel metric for hospital quality in kidney cancer surgery: a Veterans Affairs National Health System validation of concept. Urol Pract. 2022;9(3):237-245. doi:10.1097/UPJ.0000000000000294 

9. Williams SB, Janes JL, Howard LE, et al. Exposure to Agent Orange and risk of bladder cancer among US veterans. JAMA Netw Open. 2023;6(6):e2320593. doi:10.1001/jamanetworkopen.2023.20593 

10. Penn T, Borza T, Liou JI, et al. Impact of Agent Orange exposure on non-muscle invasive bladder cancer outcomes. Urology. 2023;182:175-180. doi:10.1016/j.urology.2023.08.037 

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Cancer Data Trends 2024: B-Cell Lymphoma

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Fri, 03/22/2024 - 10:44
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Cancer Data Trends 2024: B-Cell Lymphoma
References
  1. Lu W, Chen W, Zhou Y, et al. A model to predict the prognosis of diffuse large B-cell lymphoma based on ultrasound images. Sci Rep. 2023;13(1):3346. doi:10.1038/s41598-023-30533-y 

  1. Leukemia - Chronic lymphocytic - CLL: statistics. Cancer.net. Published February 2023. Accessed January 24, 2024. https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/statistics  

  1. Harmanen M, Hujo M, Sund R, et al. Survival of patients with mantle cell lymphoma in the rituximab era: retrospective binational analysis between 2000 and 2020. Br J Haematol. 2023;201(1):64-74. doi:10.1111/bjh.18597 

  1. Romancik JT, Cohen JB. Management of older adults with mantle cell lymphoma. Drugs Aging. 2020;37(7):469-481. doi:10.1007/s40266-020-00765-y 

  1. Marginal zone lymphoma (MZL). Leukemia and Lymphoma Society. Accessed January 24, 2024. https://www.lls.org/research/marginal-zone-lymphoma-mzl 

  1. Understanding lymphoma: diffuse large B-cell lymphoma. Lymphoma Research Foundation fact sheet. Updated 2023. Accessed January 24, 2024 https://lymphoma.org/wp-content/uploads/2023/10/LRF_Understanding_Lymphoma_Diffuse_Large_B_Cell_Lymphoma_Fact_Sheet.pdf 

  1. Key statistics for non-Hodgkin lymphoma. American Cancer Society. Updated January 17, 2024. Accessed January 24, 2024. https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/key-statistics.html

  1. Zullig LL, Raska W, McWhirter G, et al. Veterans Health Administration National TeleOncology Service. JCO Oncol Pract. 2023;19(4):e504-e510. doi:10.1200/OP.22.00455 

  1. Lin C, Zhou KI, Burningham ZR, et al. Telemedicine-supervised cancer therapy for patients with an aggressive lymphoma and metastatic lung cancer in the U.S. Veterans Affairs National TeleOncology Service. J Clin Oncol. 2023;41(16 suppl)16:Abstract 1602. doi:10.1200/JCO.2023.41.16_suppl.1602 

  1.  Zhang MC, Tian S, Fu D, et al. Genetic subtype-guided immunochemotherapy in diffuse large B-cell lymphoma: the randomized GUIDANCE-01 trial. Cancer Cell. 2023;41(10):1705-1716.e5. doi:10.1016/j.ccell.2023.09.004 

  1. Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389(1):33-44. doi:10.1056/NEJMoa2300696 

  1. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/s41408-021-00459-7 

  1. Caribou Biosciences reports positive clinical data from dose escalation of CB-010 ANTLER phase 1 trial in r/r B-NHL [news release]. Globalnewswire.com. Published July 13, 2023. Accessed January 24, 2024. https://www.globenewswire.com/news-release/2023/07/13/2704702/0/en/Caribou-Biosciences-Reports-Positive-Clinical-Data-from-Dose-Escalation-of-CB-010-ANTLER-Phase-1-Trial-in-r-r-B-NHL.html 

  1. Ma J, Mo Y, Tang M, et al. Bispecific antibodies: from research to clinical application. Front Immunol. 2021;12:626616. doi:10.3389/fimmu.2021.626616 

  1. Davis JA, Granger K, Sakowski A, et al. Dual target dilemma: navigating epcoritamab vs. glofitamab in relapsed refractory diffuse large B-cell lymphoma. Expert Rev Hematol. 2023;16(12):915-918. doi:10.1080/17474086.2023.2285978 

  1. Lynch RC, Poh C, Ujjani CS, et al. Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas. Blood Adv. 2023;7(11):2449-2458. doi:10.1182/bloodadvances.2022009145 

  1. Thompson PA, Tam CS. Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. Blood. 2023;141(26):3137-3142. doi:10.1182/blood.2023020240 

  1. US Food and Drug Administration. FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. Published January 19, 2023. Accessed January 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma 

  1. US Food and Drug Administration. FDA grants accelerated approval to glofitamab-gxbm for selected relapsed or refractory large B-cell lymphomas. Published June 16, 2023. Accessed January 24, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-glofitamab-gxbm-selected-relapsed-or-refractory-large-b-cell 

Author and Disclosure Information

Reviewed by Thomas Rodgers, MD
Assistant Professor, Department of Medicine
Duke University
Staff Physician, Department of Medicine
Durham VA Health System
Durham, NC

Dr. Rodgers  has no relevant financial relationships to disclose. 

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Author and Disclosure Information

Reviewed by Thomas Rodgers, MD
Assistant Professor, Department of Medicine
Duke University
Staff Physician, Department of Medicine
Durham VA Health System
Durham, NC

Dr. Rodgers  has no relevant financial relationships to disclose. 

Author and Disclosure Information

Reviewed by Thomas Rodgers, MD
Assistant Professor, Department of Medicine
Duke University
Staff Physician, Department of Medicine
Durham VA Health System
Durham, NC

Dr. Rodgers  has no relevant financial relationships to disclose. 

References
  1. Lu W, Chen W, Zhou Y, et al. A model to predict the prognosis of diffuse large B-cell lymphoma based on ultrasound images. Sci Rep. 2023;13(1):3346. doi:10.1038/s41598-023-30533-y 

  1. Leukemia - Chronic lymphocytic - CLL: statistics. Cancer.net. Published February 2023. Accessed January 24, 2024. https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/statistics  

  1. Harmanen M, Hujo M, Sund R, et al. Survival of patients with mantle cell lymphoma in the rituximab era: retrospective binational analysis between 2000 and 2020. Br J Haematol. 2023;201(1):64-74. doi:10.1111/bjh.18597 

  1. Romancik JT, Cohen JB. Management of older adults with mantle cell lymphoma. Drugs Aging. 2020;37(7):469-481. doi:10.1007/s40266-020-00765-y 

  1. Marginal zone lymphoma (MZL). Leukemia and Lymphoma Society. Accessed January 24, 2024. https://www.lls.org/research/marginal-zone-lymphoma-mzl 

  1. Understanding lymphoma: diffuse large B-cell lymphoma. Lymphoma Research Foundation fact sheet. Updated 2023. Accessed January 24, 2024 https://lymphoma.org/wp-content/uploads/2023/10/LRF_Understanding_Lymphoma_Diffuse_Large_B_Cell_Lymphoma_Fact_Sheet.pdf 

  1. Key statistics for non-Hodgkin lymphoma. American Cancer Society. Updated January 17, 2024. Accessed January 24, 2024. https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/key-statistics.html

  1. Zullig LL, Raska W, McWhirter G, et al. Veterans Health Administration National TeleOncology Service. JCO Oncol Pract. 2023;19(4):e504-e510. doi:10.1200/OP.22.00455 

  1. Lin C, Zhou KI, Burningham ZR, et al. Telemedicine-supervised cancer therapy for patients with an aggressive lymphoma and metastatic lung cancer in the U.S. Veterans Affairs National TeleOncology Service. J Clin Oncol. 2023;41(16 suppl)16:Abstract 1602. doi:10.1200/JCO.2023.41.16_suppl.1602 

  1.  Zhang MC, Tian S, Fu D, et al. Genetic subtype-guided immunochemotherapy in diffuse large B-cell lymphoma: the randomized GUIDANCE-01 trial. Cancer Cell. 2023;41(10):1705-1716.e5. doi:10.1016/j.ccell.2023.09.004 

  1. Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389(1):33-44. doi:10.1056/NEJMoa2300696 

  1. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/s41408-021-00459-7 

  1. Caribou Biosciences reports positive clinical data from dose escalation of CB-010 ANTLER phase 1 trial in r/r B-NHL [news release]. Globalnewswire.com. Published July 13, 2023. Accessed January 24, 2024. https://www.globenewswire.com/news-release/2023/07/13/2704702/0/en/Caribou-Biosciences-Reports-Positive-Clinical-Data-from-Dose-Escalation-of-CB-010-ANTLER-Phase-1-Trial-in-r-r-B-NHL.html 

  1. Ma J, Mo Y, Tang M, et al. Bispecific antibodies: from research to clinical application. Front Immunol. 2021;12:626616. doi:10.3389/fimmu.2021.626616 

  1. Davis JA, Granger K, Sakowski A, et al. Dual target dilemma: navigating epcoritamab vs. glofitamab in relapsed refractory diffuse large B-cell lymphoma. Expert Rev Hematol. 2023;16(12):915-918. doi:10.1080/17474086.2023.2285978 

  1. Lynch RC, Poh C, Ujjani CS, et al. Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas. Blood Adv. 2023;7(11):2449-2458. doi:10.1182/bloodadvances.2022009145 

  1. Thompson PA, Tam CS. Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. Blood. 2023;141(26):3137-3142. doi:10.1182/blood.2023020240 

  1. US Food and Drug Administration. FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. Published January 19, 2023. Accessed January 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma 

  1. US Food and Drug Administration. FDA grants accelerated approval to glofitamab-gxbm for selected relapsed or refractory large B-cell lymphomas. Published June 16, 2023. Accessed January 24, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-glofitamab-gxbm-selected-relapsed-or-refractory-large-b-cell 

References
  1. Lu W, Chen W, Zhou Y, et al. A model to predict the prognosis of diffuse large B-cell lymphoma based on ultrasound images. Sci Rep. 2023;13(1):3346. doi:10.1038/s41598-023-30533-y 

  1. Leukemia - Chronic lymphocytic - CLL: statistics. Cancer.net. Published February 2023. Accessed January 24, 2024. https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/statistics  

  1. Harmanen M, Hujo M, Sund R, et al. Survival of patients with mantle cell lymphoma in the rituximab era: retrospective binational analysis between 2000 and 2020. Br J Haematol. 2023;201(1):64-74. doi:10.1111/bjh.18597 

  1. Romancik JT, Cohen JB. Management of older adults with mantle cell lymphoma. Drugs Aging. 2020;37(7):469-481. doi:10.1007/s40266-020-00765-y 

  1. Marginal zone lymphoma (MZL). Leukemia and Lymphoma Society. Accessed January 24, 2024. https://www.lls.org/research/marginal-zone-lymphoma-mzl 

  1. Understanding lymphoma: diffuse large B-cell lymphoma. Lymphoma Research Foundation fact sheet. Updated 2023. Accessed January 24, 2024 https://lymphoma.org/wp-content/uploads/2023/10/LRF_Understanding_Lymphoma_Diffuse_Large_B_Cell_Lymphoma_Fact_Sheet.pdf 

  1. Key statistics for non-Hodgkin lymphoma. American Cancer Society. Updated January 17, 2024. Accessed January 24, 2024. https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/key-statistics.html

  1. Zullig LL, Raska W, McWhirter G, et al. Veterans Health Administration National TeleOncology Service. JCO Oncol Pract. 2023;19(4):e504-e510. doi:10.1200/OP.22.00455 

  1. Lin C, Zhou KI, Burningham ZR, et al. Telemedicine-supervised cancer therapy for patients with an aggressive lymphoma and metastatic lung cancer in the U.S. Veterans Affairs National TeleOncology Service. J Clin Oncol. 2023;41(16 suppl)16:Abstract 1602. doi:10.1200/JCO.2023.41.16_suppl.1602 

  1.  Zhang MC, Tian S, Fu D, et al. Genetic subtype-guided immunochemotherapy in diffuse large B-cell lymphoma: the randomized GUIDANCE-01 trial. Cancer Cell. 2023;41(10):1705-1716.e5. doi:10.1016/j.ccell.2023.09.004 

  1. Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389(1):33-44. doi:10.1056/NEJMoa2300696 

  1. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/s41408-021-00459-7 

  1. Caribou Biosciences reports positive clinical data from dose escalation of CB-010 ANTLER phase 1 trial in r/r B-NHL [news release]. Globalnewswire.com. Published July 13, 2023. Accessed January 24, 2024. https://www.globenewswire.com/news-release/2023/07/13/2704702/0/en/Caribou-Biosciences-Reports-Positive-Clinical-Data-from-Dose-Escalation-of-CB-010-ANTLER-Phase-1-Trial-in-r-r-B-NHL.html 

  1. Ma J, Mo Y, Tang M, et al. Bispecific antibodies: from research to clinical application. Front Immunol. 2021;12:626616. doi:10.3389/fimmu.2021.626616 

  1. Davis JA, Granger K, Sakowski A, et al. Dual target dilemma: navigating epcoritamab vs. glofitamab in relapsed refractory diffuse large B-cell lymphoma. Expert Rev Hematol. 2023;16(12):915-918. doi:10.1080/17474086.2023.2285978 

  1. Lynch RC, Poh C, Ujjani CS, et al. Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas. Blood Adv. 2023;7(11):2449-2458. doi:10.1182/bloodadvances.2022009145 

  1. Thompson PA, Tam CS. Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. Blood. 2023;141(26):3137-3142. doi:10.1182/blood.2023020240 

  1. US Food and Drug Administration. FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. Published January 19, 2023. Accessed January 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma 

  1. US Food and Drug Administration. FDA grants accelerated approval to glofitamab-gxbm for selected relapsed or refractory large B-cell lymphomas. Published June 16, 2023. Accessed January 24, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-glofitamab-gxbm-selected-relapsed-or-refractory-large-b-cell 

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Not Even Secondary Endpoints Support BTK Inhibitor in Phase 3 MS Trial

Article Type
Changed
Fri, 03/15/2024 - 12:58

— Top-line results of two phase 3 trials evaluating the BTK inhibitor evobrutinib for treatment of multiple sclerosis (MS) were negative when released several months ago, but the hope for a signal of benefit on secondary endpoints was dashed when the full results of the trials were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.

Based on prior drug development, including the promise seen in a phase 2 trial, “these negative results were quite disappointing,” reported Xavier Montalban, MD, director, department of neurology, Catalunya Center for Multiple Sclerosis, Hospital Universitario Vall d’Hebron, Barcelona, Spain.

In the evolutionRMS1 and 2 phase 3 trials, 2285 relapsing-remitting MS patients with active disease were randomized to 45 mg of twice-daily oral evobrutinib or 14 mg once-daily teriflunomide, a pyrimidine synthesis inhibitor already widely used for the treatment of MS. The trial, conducted in 52 countries, was double-blind and double-dummy.

Ted Bosworth/MDedge News
Dr. Xavier Montalban


When released at the end of 2023, the primary endpoints of the annualized relapse rate (ARR) were identical or nearly identical for evobrutinib relative to teriflunomide in RMS1 (0.15 vs 0.14) and RMS2 (0.11 vs 0.11).

Yet, many researchers were still hoping to see some greater advantage for the BTK inhibitor, which modulates B cell activity and inhibits activation of inflammatory cells in the central nervous system, on one or more secondary endpoints.

“The primary ARR endpoint was mandated by the regulatory agencies,” explained Mark S. Freedman, MD, director of the MS Research Unit, University of Ottawa, Canada. Although he was not greatly surprised that evobrutinib failed to show superiority over the already low ARR rates typically achieved on teriflunomide, he had held out hope that a benefit on one or more secondary outcomes would support BTK inhibition as an MS target.

However, the time to confirmed disability progression and time to confirmed disability improvement among the two treatment groups traced the same course over 24 weeks. Graphically, the lines were nearly superimposed.
 

No Outcome Supported an Evobrutinib Advantage

Numerically, the mean number of T1 gadolinium-enhancing lesions was greater among those randomized to evobrutinib while the mean number of new or enlarging T2 lesions was lower. However, none of these differences in either study reached statistical significance.

The lower serum neurofilament light chain (sNfL) levels were significant (P = .032) in one of the two trials, but the difference was modest, and Dr. Montalban stated that the difference “was probably not clinically significant.”

Almost all of the patients had multiple relapses before being enrolled in the study, but only 36.5% had received a prior disease-modifying therapy. According to Dr. Montalban, the baseline characteristics of the patients enrolled were “nothing special,” in that they were very much “like the types of patients enrolled in trials like these.”

In general, both drugs were well tolerated with a comparable safety profile. The exception was a greater proportion of patients randomized to evobrutinib who developed elevated liver function tests, including a greater proportion with a level at least 5 times the upper limit of normal. All normalized after treatment was discontinued.

This is the first phase 3 trial of a BTK inhibitor in MS, according to Dr. Montalban, who pointed out that evobrutinib did perform as well as a highly active agent, even if it could not show superiority.

There is limited likelihood that further ongoing analyses will uncover meaningful activity not detected in the primary and secondary outcomes, but Dr. Montalban said that there is a possibility that a higher dose or a BTK inhibitor with different characteristics might still produce the types of clinical benefits hypothesized in this initial trial.

Asked to speculate about the results if the RM1 and RM2 trials had a noninferiority rather than a superiority design been employed, Dr. Montalban said that evobrutinib relative to teriflunomide appears to be “similar but more toxic.”

The recent excitement building for the potential of BTK inhibitors in MS was not helped by a second, but much smaller, late-breaker study that evaluated tolebrutinib. The primary endpoint of that study, conducted with just seven patients, was complete resolution of paramagnetic rim lesions (PRL), a prognostically important composition of macrophages, microglia, and iron seen in the central nervous system (CNS) on imaging.
 

 

 

No Resolution of CNS Lesions

Even after 48 weeks, none of the lesions had resolved, according to Maria I. Gaitán, MD, acting director of the Translational Neuroradiology Unit of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland.

Again, although these findings were disappointing, Dr. Gaitán said there are a number of explanations for the result that do not preclude a benefit from BTK inhibitors in future studies.

“Complete resolution of PRL might be a bar that was too high,” she said, noting that favorable changes in these lesions could have occurred even if the characteristic iron deposits persisted. She also suggested that dosing might not have been optimized to halt or reverse disease activity in the CNS. Like Dr. Montalban, she suggested that BTK inhibitors with different characteristics might succeed where tolebrutinib failed.

Dr. Freedman, current president of ACTRIMS, agreed that these data should not be interpreted as ruling out a clinical role for BTK inhibitors. Pointing to the substantial body of data supporting this mechanism for reversing inflammation in the CNS, he declared that “the story is not over.”

Dr. Montalban reported financial relationships with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman La Roche, Immunic, Janssen, Mylan, NervGen, Novartis, Sanofi-Genzyme, Teva, TG Therapeutics, and Merck, which provided funding for the RMS 1 and 2 trials. Dr. Freedman reported financial relationships with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Hoffman La Roche, Merck, Novartis, and Teva Canada Innovation. Dr. Gaitán reported no potential conflicts of interest.

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— Top-line results of two phase 3 trials evaluating the BTK inhibitor evobrutinib for treatment of multiple sclerosis (MS) were negative when released several months ago, but the hope for a signal of benefit on secondary endpoints was dashed when the full results of the trials were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.

Based on prior drug development, including the promise seen in a phase 2 trial, “these negative results were quite disappointing,” reported Xavier Montalban, MD, director, department of neurology, Catalunya Center for Multiple Sclerosis, Hospital Universitario Vall d’Hebron, Barcelona, Spain.

In the evolutionRMS1 and 2 phase 3 trials, 2285 relapsing-remitting MS patients with active disease were randomized to 45 mg of twice-daily oral evobrutinib or 14 mg once-daily teriflunomide, a pyrimidine synthesis inhibitor already widely used for the treatment of MS. The trial, conducted in 52 countries, was double-blind and double-dummy.

Ted Bosworth/MDedge News
Dr. Xavier Montalban


When released at the end of 2023, the primary endpoints of the annualized relapse rate (ARR) were identical or nearly identical for evobrutinib relative to teriflunomide in RMS1 (0.15 vs 0.14) and RMS2 (0.11 vs 0.11).

Yet, many researchers were still hoping to see some greater advantage for the BTK inhibitor, which modulates B cell activity and inhibits activation of inflammatory cells in the central nervous system, on one or more secondary endpoints.

“The primary ARR endpoint was mandated by the regulatory agencies,” explained Mark S. Freedman, MD, director of the MS Research Unit, University of Ottawa, Canada. Although he was not greatly surprised that evobrutinib failed to show superiority over the already low ARR rates typically achieved on teriflunomide, he had held out hope that a benefit on one or more secondary outcomes would support BTK inhibition as an MS target.

However, the time to confirmed disability progression and time to confirmed disability improvement among the two treatment groups traced the same course over 24 weeks. Graphically, the lines were nearly superimposed.
 

No Outcome Supported an Evobrutinib Advantage

Numerically, the mean number of T1 gadolinium-enhancing lesions was greater among those randomized to evobrutinib while the mean number of new or enlarging T2 lesions was lower. However, none of these differences in either study reached statistical significance.

The lower serum neurofilament light chain (sNfL) levels were significant (P = .032) in one of the two trials, but the difference was modest, and Dr. Montalban stated that the difference “was probably not clinically significant.”

Almost all of the patients had multiple relapses before being enrolled in the study, but only 36.5% had received a prior disease-modifying therapy. According to Dr. Montalban, the baseline characteristics of the patients enrolled were “nothing special,” in that they were very much “like the types of patients enrolled in trials like these.”

In general, both drugs were well tolerated with a comparable safety profile. The exception was a greater proportion of patients randomized to evobrutinib who developed elevated liver function tests, including a greater proportion with a level at least 5 times the upper limit of normal. All normalized after treatment was discontinued.

This is the first phase 3 trial of a BTK inhibitor in MS, according to Dr. Montalban, who pointed out that evobrutinib did perform as well as a highly active agent, even if it could not show superiority.

There is limited likelihood that further ongoing analyses will uncover meaningful activity not detected in the primary and secondary outcomes, but Dr. Montalban said that there is a possibility that a higher dose or a BTK inhibitor with different characteristics might still produce the types of clinical benefits hypothesized in this initial trial.

Asked to speculate about the results if the RM1 and RM2 trials had a noninferiority rather than a superiority design been employed, Dr. Montalban said that evobrutinib relative to teriflunomide appears to be “similar but more toxic.”

The recent excitement building for the potential of BTK inhibitors in MS was not helped by a second, but much smaller, late-breaker study that evaluated tolebrutinib. The primary endpoint of that study, conducted with just seven patients, was complete resolution of paramagnetic rim lesions (PRL), a prognostically important composition of macrophages, microglia, and iron seen in the central nervous system (CNS) on imaging.
 

 

 

No Resolution of CNS Lesions

Even after 48 weeks, none of the lesions had resolved, according to Maria I. Gaitán, MD, acting director of the Translational Neuroradiology Unit of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland.

Again, although these findings were disappointing, Dr. Gaitán said there are a number of explanations for the result that do not preclude a benefit from BTK inhibitors in future studies.

“Complete resolution of PRL might be a bar that was too high,” she said, noting that favorable changes in these lesions could have occurred even if the characteristic iron deposits persisted. She also suggested that dosing might not have been optimized to halt or reverse disease activity in the CNS. Like Dr. Montalban, she suggested that BTK inhibitors with different characteristics might succeed where tolebrutinib failed.

Dr. Freedman, current president of ACTRIMS, agreed that these data should not be interpreted as ruling out a clinical role for BTK inhibitors. Pointing to the substantial body of data supporting this mechanism for reversing inflammation in the CNS, he declared that “the story is not over.”

Dr. Montalban reported financial relationships with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman La Roche, Immunic, Janssen, Mylan, NervGen, Novartis, Sanofi-Genzyme, Teva, TG Therapeutics, and Merck, which provided funding for the RMS 1 and 2 trials. Dr. Freedman reported financial relationships with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Hoffman La Roche, Merck, Novartis, and Teva Canada Innovation. Dr. Gaitán reported no potential conflicts of interest.

— Top-line results of two phase 3 trials evaluating the BTK inhibitor evobrutinib for treatment of multiple sclerosis (MS) were negative when released several months ago, but the hope for a signal of benefit on secondary endpoints was dashed when the full results of the trials were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum.

Based on prior drug development, including the promise seen in a phase 2 trial, “these negative results were quite disappointing,” reported Xavier Montalban, MD, director, department of neurology, Catalunya Center for Multiple Sclerosis, Hospital Universitario Vall d’Hebron, Barcelona, Spain.

In the evolutionRMS1 and 2 phase 3 trials, 2285 relapsing-remitting MS patients with active disease were randomized to 45 mg of twice-daily oral evobrutinib or 14 mg once-daily teriflunomide, a pyrimidine synthesis inhibitor already widely used for the treatment of MS. The trial, conducted in 52 countries, was double-blind and double-dummy.

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Dr. Xavier Montalban


When released at the end of 2023, the primary endpoints of the annualized relapse rate (ARR) were identical or nearly identical for evobrutinib relative to teriflunomide in RMS1 (0.15 vs 0.14) and RMS2 (0.11 vs 0.11).

Yet, many researchers were still hoping to see some greater advantage for the BTK inhibitor, which modulates B cell activity and inhibits activation of inflammatory cells in the central nervous system, on one or more secondary endpoints.

“The primary ARR endpoint was mandated by the regulatory agencies,” explained Mark S. Freedman, MD, director of the MS Research Unit, University of Ottawa, Canada. Although he was not greatly surprised that evobrutinib failed to show superiority over the already low ARR rates typically achieved on teriflunomide, he had held out hope that a benefit on one or more secondary outcomes would support BTK inhibition as an MS target.

However, the time to confirmed disability progression and time to confirmed disability improvement among the two treatment groups traced the same course over 24 weeks. Graphically, the lines were nearly superimposed.
 

No Outcome Supported an Evobrutinib Advantage

Numerically, the mean number of T1 gadolinium-enhancing lesions was greater among those randomized to evobrutinib while the mean number of new or enlarging T2 lesions was lower. However, none of these differences in either study reached statistical significance.

The lower serum neurofilament light chain (sNfL) levels were significant (P = .032) in one of the two trials, but the difference was modest, and Dr. Montalban stated that the difference “was probably not clinically significant.”

Almost all of the patients had multiple relapses before being enrolled in the study, but only 36.5% had received a prior disease-modifying therapy. According to Dr. Montalban, the baseline characteristics of the patients enrolled were “nothing special,” in that they were very much “like the types of patients enrolled in trials like these.”

In general, both drugs were well tolerated with a comparable safety profile. The exception was a greater proportion of patients randomized to evobrutinib who developed elevated liver function tests, including a greater proportion with a level at least 5 times the upper limit of normal. All normalized after treatment was discontinued.

This is the first phase 3 trial of a BTK inhibitor in MS, according to Dr. Montalban, who pointed out that evobrutinib did perform as well as a highly active agent, even if it could not show superiority.

There is limited likelihood that further ongoing analyses will uncover meaningful activity not detected in the primary and secondary outcomes, but Dr. Montalban said that there is a possibility that a higher dose or a BTK inhibitor with different characteristics might still produce the types of clinical benefits hypothesized in this initial trial.

Asked to speculate about the results if the RM1 and RM2 trials had a noninferiority rather than a superiority design been employed, Dr. Montalban said that evobrutinib relative to teriflunomide appears to be “similar but more toxic.”

The recent excitement building for the potential of BTK inhibitors in MS was not helped by a second, but much smaller, late-breaker study that evaluated tolebrutinib. The primary endpoint of that study, conducted with just seven patients, was complete resolution of paramagnetic rim lesions (PRL), a prognostically important composition of macrophages, microglia, and iron seen in the central nervous system (CNS) on imaging.
 

 

 

No Resolution of CNS Lesions

Even after 48 weeks, none of the lesions had resolved, according to Maria I. Gaitán, MD, acting director of the Translational Neuroradiology Unit of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland.

Again, although these findings were disappointing, Dr. Gaitán said there are a number of explanations for the result that do not preclude a benefit from BTK inhibitors in future studies.

“Complete resolution of PRL might be a bar that was too high,” she said, noting that favorable changes in these lesions could have occurred even if the characteristic iron deposits persisted. She also suggested that dosing might not have been optimized to halt or reverse disease activity in the CNS. Like Dr. Montalban, she suggested that BTK inhibitors with different characteristics might succeed where tolebrutinib failed.

Dr. Freedman, current president of ACTRIMS, agreed that these data should not be interpreted as ruling out a clinical role for BTK inhibitors. Pointing to the substantial body of data supporting this mechanism for reversing inflammation in the CNS, he declared that “the story is not over.”

Dr. Montalban reported financial relationships with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman La Roche, Immunic, Janssen, Mylan, NervGen, Novartis, Sanofi-Genzyme, Teva, TG Therapeutics, and Merck, which provided funding for the RMS 1 and 2 trials. Dr. Freedman reported financial relationships with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Hoffman La Roche, Merck, Novartis, and Teva Canada Innovation. Dr. Gaitán reported no potential conflicts of interest.

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Long-term Fremanezumab Effective and Safe in Hard-to-Treat Migraine

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Sun, 03/31/2024 - 19:07

Key clinical point: Long-term fremanezumab treatment appears to be highly effective, safe, and well tolerated in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who have experienced multiple (more than three) treatment failures and have various comorbidities.

Major finding: At 48 weeks, fremanezumab led to significant reductions in the monthly migraine days in patients with HFEM (mean change −6.4 days) and monthly headache days in patients with CM (mean change −14.5 days; both P < .001). Overall, 7.8% of patients reported mild and transient treatment-emergent adverse events, and none of the patients discontinued the treatment for any reason.

Study details: This prospective, multicenter, cohort study included 130 patients with migraine (49 with HEFM; 81 with CM) and multiple treatment failures who received fremanezumab for at least 48 weeks (≥ 12 doses).

Disclosures: This study was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) San Raffaele and Fondazione Italiana Cefalee. Several authors declared receiving travel grants, research support, or honoraria from or having other ties with various sources. Twenty authors declared no conflicts of interest.

Source: Barbanti P, Egeo G, Proietti S, et al for the Italian Migraine Registry study group. Assessing the long-term (48-week) effectiveness, safety, and tolerability of fremanezumab in migraine in real life: Insights from the multicenter, prospective, FRIEND3 study. Neurol Ther. 2024 (Mar 7). doi: 10.1007/s40120-024-00591-z Source

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Key clinical point: Long-term fremanezumab treatment appears to be highly effective, safe, and well tolerated in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who have experienced multiple (more than three) treatment failures and have various comorbidities.

Major finding: At 48 weeks, fremanezumab led to significant reductions in the monthly migraine days in patients with HFEM (mean change −6.4 days) and monthly headache days in patients with CM (mean change −14.5 days; both P < .001). Overall, 7.8% of patients reported mild and transient treatment-emergent adverse events, and none of the patients discontinued the treatment for any reason.

Study details: This prospective, multicenter, cohort study included 130 patients with migraine (49 with HEFM; 81 with CM) and multiple treatment failures who received fremanezumab for at least 48 weeks (≥ 12 doses).

Disclosures: This study was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) San Raffaele and Fondazione Italiana Cefalee. Several authors declared receiving travel grants, research support, or honoraria from or having other ties with various sources. Twenty authors declared no conflicts of interest.

Source: Barbanti P, Egeo G, Proietti S, et al for the Italian Migraine Registry study group. Assessing the long-term (48-week) effectiveness, safety, and tolerability of fremanezumab in migraine in real life: Insights from the multicenter, prospective, FRIEND3 study. Neurol Ther. 2024 (Mar 7). doi: 10.1007/s40120-024-00591-z Source

Key clinical point: Long-term fremanezumab treatment appears to be highly effective, safe, and well tolerated in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who have experienced multiple (more than three) treatment failures and have various comorbidities.

Major finding: At 48 weeks, fremanezumab led to significant reductions in the monthly migraine days in patients with HFEM (mean change −6.4 days) and monthly headache days in patients with CM (mean change −14.5 days; both P < .001). Overall, 7.8% of patients reported mild and transient treatment-emergent adverse events, and none of the patients discontinued the treatment for any reason.

Study details: This prospective, multicenter, cohort study included 130 patients with migraine (49 with HEFM; 81 with CM) and multiple treatment failures who received fremanezumab for at least 48 weeks (≥ 12 doses).

Disclosures: This study was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) San Raffaele and Fondazione Italiana Cefalee. Several authors declared receiving travel grants, research support, or honoraria from or having other ties with various sources. Twenty authors declared no conflicts of interest.

Source: Barbanti P, Egeo G, Proietti S, et al for the Italian Migraine Registry study group. Assessing the long-term (48-week) effectiveness, safety, and tolerability of fremanezumab in migraine in real life: Insights from the multicenter, prospective, FRIEND3 study. Neurol Ther. 2024 (Mar 7). doi: 10.1007/s40120-024-00591-z Source

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Clinical Edge Journal Scan: Migraine, April 2024
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