Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609

Laurie E. McLouth; Yue Zheng; Stephanie Smith; F. Stephen Hodi; Uma N. Rao; Gary I. Cohen; Thomas T. Amatruda; Shaker R. Dakhil; Brendan D. Curti; Ibrahim Nakhoul; Sreenivasa R. Chandana; Charles L. Bane; David E. Marinier; Sandra J. Lee; Vernon K. Sondak; John M. Kirkwood; Ahmad A. Tarhini; Lynne I. Wagner

doi:10.1007/s11136-022-03226-8

Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609

Laurie E. McLouth, Yue Zheng, Stephanie Smith, F. Stephen Hodi, Uma N. Rao, Gary I. Cohen, Thomas T. Amatruda, Shaker R. Dakhil, Brendan D. Curti, Ibrahim Nakhoul, Sreenivasa R. Chandana, Charles L. Bane, David E. Marinier, Sandra J. Lee, Vernon K. Sondak, John M. Kirkwood, Ahmad A. Tarhini, Lynne I. Wagner

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. Methods: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. Results: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p <.001; ipi10 = 84.9 ± 16.5 vs. HDI, p <.001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p <.001; ipi10 = 21.8 ± 5.0 vs. HDI p <.001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p <.001; ipi10 = 17.7 ± 4.8 vs. HDI p <.001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p =.011; ipi10 = 39.5 ± 7.0 vs. HDI, p <.001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p’s <.001). Conclusion: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. Trial Registration: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1.

Original language	English
Pages (from-to)	183-196
Number of pages	14
Journal	Quality of Life Research
Volume	32
Issue number	1
DOIs	https://doi.org/10.1007/s11136-022-03226-8
State	Published - Jan 2023

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Funding

This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: UG1CA233184, U10CA180794, UG1CA189823, U10CA180821, UG1CA189828, U10CA180820, UG1CA189867, U10CA180868, UG1CA189974, U10CA180888, UG1CA189860, UG1CA189863, UG1CA189953, UG1CA189956, UG1CA189957, UG1CA233180, UG1CA233196, and UG1CA189858. Dr. McLouth’s effort on this manuscript was supported by R25CA122061, P30 CA1777558, and 2KL2TR001996-05A1.

Funders	Funder number
National Institutes of Health (NIH)	2KL2TR001996-05A1, U10CA180820, U10CA180794, UG1CA189860, P30 CA1777558, R25CA122061, UG1CA189828, UG1CA233180, UG1CA189863, UG1CA189974, UG1CA189953, UG1CA233196, UG1CA233184, U10CA180868, UG1CA189823, UG1CA189867, UG1CA189956, U10CA180888, UG1CA189858, UG1CA189957, U10CA180821
National Childhood Cancer Registry – National Cancer Institute

Keywords

Adjuvant therapy
Interferon
Ipilimumab
Melanoma
Patient-reported outcomes
Quality of life

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s11136-022-03226-8

Cite this

McLouth, L. E., Zheng, Y., Smith, S., Hodi, F. S., Rao, U. N., Cohen, G. I., Amatruda, T. T., Dakhil, S. R., Curti, B. D., Nakhoul, I., Chandana, S. R., Bane, C. L., Marinier, D. E., Lee, S. J., Sondak, V. K., Kirkwood, J. M., Tarhini, A. A., & Wagner, L. I. (2023). Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609. Quality of Life Research, 32(1), 183-196. https://doi.org/10.1007/s11136-022-03226-8

@article{5b7d0edf32624b6685412abd7011dde9,

title = "Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609",

abstract = "Purpose: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. Methods: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. Results: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p <.001; ipi10 = 84.9 ± 16.5 vs. HDI, p <.001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p <.001; ipi10 = 21.8 ± 5.0 vs. HDI p <.001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p <.001; ipi10 = 17.7 ± 4.8 vs. HDI p <.001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p =.011; ipi10 = 39.5 ± 7.0 vs. HDI, p <.001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p{\textquoteright}s <.001). Conclusion: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. Trial Registration: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1.",

keywords = "Adjuvant therapy, Interferon, Ipilimumab, Melanoma, Patient-reported outcomes, Quality of life",

author = "McLouth, {Laurie E.} and Yue Zheng and Stephanie Smith and Hodi, {F. Stephen} and Rao, {Uma N.} and Cohen, {Gary I.} and Amatruda, {Thomas T.} and Dakhil, {Shaker R.} and Curti, {Brendan D.} and Ibrahim Nakhoul and Chandana, {Sreenivasa R.} and Bane, {Charles L.} and Marinier, {David E.} and Lee, {Sandra J.} and Sondak, {Vernon K.} and Kirkwood, {John M.} and Tarhini, {Ahmad A.} and Wagner, {Lynne I.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.",

year = "2023",

month = jan,

doi = "10.1007/s11136-022-03226-8",

language = "English",

volume = "32",

pages = "183--196",

number = "1",

}

McLouth, LE, Zheng, Y, Smith, S, Hodi, FS, Rao, UN, Cohen, GI, Amatruda, TT, Dakhil, SR, Curti, BD, Nakhoul, I, Chandana, SR, Bane, CL, Marinier, DE, Lee, SJ, Sondak, VK, Kirkwood, JM, Tarhini, AA & Wagner, LI 2023, 'Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609', Quality of Life Research, vol. 32, no. 1, pp. 183-196. https://doi.org/10.1007/s11136-022-03226-8

Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609. / McLouth, Laurie E.; Zheng, Yue; Smith, Stephanie et al.
In: Quality of Life Research, Vol. 32, No. 1, 01.2023, p. 183-196.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III–IV melanoma in phase III trial E1609

AU - McLouth, Laurie E.

AU - Zheng, Yue

AU - Smith, Stephanie

AU - Hodi, F. Stephen

AU - Rao, Uma N.

AU - Cohen, Gary I.

AU - Amatruda, Thomas T.

AU - Dakhil, Shaker R.

AU - Curti, Brendan D.

AU - Nakhoul, Ibrahim

AU - Chandana, Sreenivasa R.

AU - Bane, Charles L.

AU - Marinier, David E.

AU - Lee, Sandra J.

AU - Sondak, Vernon K.

AU - Kirkwood, John M.

AU - Tarhini, Ahmad A.

AU - Wagner, Lynne I.

PY - 2023/1

Y1 - 2023/1

N2 - Purpose: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. Methods: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. Results: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p <.001; ipi10 = 84.9 ± 16.5 vs. HDI, p <.001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p <.001; ipi10 = 21.8 ± 5.0 vs. HDI p <.001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p <.001; ipi10 = 17.7 ± 4.8 vs. HDI p <.001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p =.011; ipi10 = 39.5 ± 7.0 vs. HDI, p <.001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p’s <.001). Conclusion: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. Trial Registration: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1.

AB - Purpose: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. Methods: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. Results: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p <.001; ipi10 = 84.9 ± 16.5 vs. HDI, p <.001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p <.001; ipi10 = 21.8 ± 5.0 vs. HDI p <.001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p <.001; ipi10 = 17.7 ± 4.8 vs. HDI p <.001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p =.011; ipi10 = 39.5 ± 7.0 vs. HDI, p <.001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p’s <.001). Conclusion: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. Trial Registration: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1.

KW - Adjuvant therapy

KW - Interferon

KW - Ipilimumab

KW - Melanoma

KW - Patient-reported outcomes

KW - Quality of life

UR - http://www.scopus.com/inward/record.url?scp=85136694546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85136694546&partnerID=8YFLogxK

U2 - 10.1007/s11136-022-03226-8

DO - 10.1007/s11136-022-03226-8

M3 - Article

C2 - 36029412

AN - SCOPUS:85136694546

SN - 0962-9343

VL - 32

SP - 183

EP - 196

JO - Quality of Life Research

JF - Quality of Life Research

IS - 1

ER -