Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database

TY - JOUR

T1 - Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database

AU - Franko, Jan

AU - Yin, Jun

AU - Adams, Richard A

AU - Zalcberg, John

AU - Fiskum, Jack

AU - Van Cutsem, Eric

AU - Goldberg, Richard M

AU - Hurwitz, Herbert

AU - Bokemeyer, Carsten

AU - Kabbinavar, Fairooz

AU - Curtis, Alexandra

AU - Meyers, Jeffery

AU - Chibaudel, Benoist

AU - Yoshino, Takayuki

AU - de Gramont, Aimery

AU - Shi, Qian

AU - ARCAD collaborators

N1 - Copyright © 2022 Elsevier Ltd. All rights reserved.

PY - 2022/10

Y1 - 2022/10

N2 - BACKGROUND: Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown.METHODS: We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight.FINDINGS: Data were available for 3504 patients. The median weight change at 3 months was -0.54% (IQR -3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06-1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67-2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites.INTERPRETATION: Patients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point.FUNDING: The creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.

AB - BACKGROUND: Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown.METHODS: We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight.FINDINGS: Data were available for 3504 patients. The median weight change at 3 months was -0.54% (IQR -3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06-1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67-2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites.INTERPRETATION: Patients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point.FUNDING: The creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.

U2 - 10.1016/j.ejca.2022.07.021

DO - 10.1016/j.ejca.2022.07.021

M3 - SCORING: Journal article

C2 - 35994794

VL - 174

SP - 142

EP - 152

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

ER -