Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma

Radhakrishnan Ramchandren, Ranjana H. Advani, Stephen Maxted Ansell, Nancy L. Bartlett, Robert Chen, Joseph M. Connors, Tatyana Feldman, Andres Forero-Torres, Jonathan W. Friedberg, Ajay K. Gopal, Leo I. Gordon, John Kuruvilla, Kerry J. Savage, Anas Younes, Gerald Engley, Thomas J. Manley, Keenan Fenton, David J. Straus

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA). Patients and Methods: ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (AþAVD) versus ABVD (AVD þ bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive AþAVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. Results: The NA subgroup consisted of 497 subjects in the AþAVD (n ¼ 250) and ABVD (n ¼ 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received AþAVD compared with ABVD (HR ¼ 0.60; P ¼ 0.012). For PFS, the risk of progression or death was also reduced (HR ¼ 0.50; P ¼ 0.002). Subsequent anticancer therapies were lower in the AþAVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the AþAVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated with AþAVD versus ABVD. Conclusions: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support AþAVD as a frontline treatment option for patients with stage III or IV cHL.

Original languageEnglish (US)
Pages (from-to)1718-1726
Number of pages9
JournalClinical Cancer Research
Volume25
Issue number6
DOIs
StatePublished - Jan 1 2019

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North America
Hodgkin Disease
Drug Therapy
Disease-Free Survival
Febrile Neutropenia
Dacarbazine
Vinblastine
Bleomycin
Peripheral Nervous System Diseases
Doxorubicin
Therapeutics
Safety
Lung
Population
cAC10-vcMMAE

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma. / Ramchandren, Radhakrishnan; Advani, Ranjana H.; Ansell, Stephen Maxted; Bartlett, Nancy L.; Chen, Robert; Connors, Joseph M.; Feldman, Tatyana; Forero-Torres, Andres; Friedberg, Jonathan W.; Gopal, Ajay K.; Gordon, Leo I.; Kuruvilla, John; Savage, Kerry J.; Younes, Anas; Engley, Gerald; Manley, Thomas J.; Fenton, Keenan; Straus, David J.

In: Clinical Cancer Research, Vol. 25, No. 6, 01.01.2019, p. 1718-1726.

Research output: Contribution to journalArticle

Ramchandren, R, Advani, RH, Ansell, SM, Bartlett, NL, Chen, R, Connors, JM, Feldman, T, Forero-Torres, A, Friedberg, JW, Gopal, AK, Gordon, LI, Kuruvilla, J, Savage, KJ, Younes, A, Engley, G, Manley, TJ, Fenton, K & Straus, DJ 2019, 'Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma', Clinical Cancer Research, vol. 25, no. 6, pp. 1718-1726. https://doi.org/10.1158/1078-0432.CCR-18-2435
Ramchandren, Radhakrishnan ; Advani, Ranjana H. ; Ansell, Stephen Maxted ; Bartlett, Nancy L. ; Chen, Robert ; Connors, Joseph M. ; Feldman, Tatyana ; Forero-Torres, Andres ; Friedberg, Jonathan W. ; Gopal, Ajay K. ; Gordon, Leo I. ; Kuruvilla, John ; Savage, Kerry J. ; Younes, Anas ; Engley, Gerald ; Manley, Thomas J. ; Fenton, Keenan ; Straus, David J. / Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 6. pp. 1718-1726.
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abstract = "Purpose: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA). Patients and Methods: ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (A{\th}AVD) versus ABVD (AVD {\th} bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive A{\th}AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. Results: The NA subgroup consisted of 497 subjects in the A{\th}AVD (n ¼ 250) and ABVD (n ¼ 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received A{\th}AVD compared with ABVD (HR ¼ 0.60; P ¼ 0.012). For PFS, the risk of progression or death was also reduced (HR ¼ 0.50; P ¼ 0.002). Subsequent anticancer therapies were lower in the A{\th}AVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the A{\th}AVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20{\%} vs. 9{\%}) and peripheral neuropathy (80{\%} vs. 56{\%}), but lower rates of pulmonary toxicity (3{\%} vs. 10{\%}) in subjects treated with A{\th}AVD versus ABVD. Conclusions: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support A{\th}AVD as a frontline treatment option for patients with stage III or IV cHL.",
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T1 - Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma

AU - Ramchandren, Radhakrishnan

AU - Advani, Ranjana H.

AU - Ansell, Stephen Maxted

AU - Bartlett, Nancy L.

AU - Chen, Robert

AU - Connors, Joseph M.

AU - Feldman, Tatyana

AU - Forero-Torres, Andres

AU - Friedberg, Jonathan W.

AU - Gopal, Ajay K.

AU - Gordon, Leo I.

AU - Kuruvilla, John

AU - Savage, Kerry J.

AU - Younes, Anas

AU - Engley, Gerald

AU - Manley, Thomas J.

AU - Fenton, Keenan

AU - Straus, David J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA). Patients and Methods: ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (AþAVD) versus ABVD (AVD þ bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive AþAVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. Results: The NA subgroup consisted of 497 subjects in the AþAVD (n ¼ 250) and ABVD (n ¼ 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received AþAVD compared with ABVD (HR ¼ 0.60; P ¼ 0.012). For PFS, the risk of progression or death was also reduced (HR ¼ 0.50; P ¼ 0.002). Subsequent anticancer therapies were lower in the AþAVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the AþAVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated with AþAVD versus ABVD. Conclusions: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support AþAVD as a frontline treatment option for patients with stage III or IV cHL.

AB - Purpose: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA). Patients and Methods: ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (AþAVD) versus ABVD (AVD þ bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive AþAVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. Results: The NA subgroup consisted of 497 subjects in the AþAVD (n ¼ 250) and ABVD (n ¼ 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received AþAVD compared with ABVD (HR ¼ 0.60; P ¼ 0.012). For PFS, the risk of progression or death was also reduced (HR ¼ 0.50; P ¼ 0.002). Subsequent anticancer therapies were lower in the AþAVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the AþAVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated with AþAVD versus ABVD. Conclusions: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support AþAVD as a frontline treatment option for patients with stage III or IV cHL.

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