Weight loss over time and survival: a landmark analysis of 1000+ prospectively treated and monitored lung cancer patients

Abstract

Background Eligibility criteria and endpoints for cancer cachexia trials-and whether weight loss should be included-remain controversial. Although most cachexia trials enrol patients after initial cancer diagnosis, few studies have addressed whether weight loss well after a cancer diagnosis is prognostic. Methods We pooled data from non-small cell lung cancer patients from prospectively conducted trials within the Alliance for Clinical Trials in Oncology (1998-2008), a nationally funded infrastructure. We examined (i) weight data availability and weight changes and (ii) survival. Results A total of 822 patients were examined. Of these, 659 (80%) were on treatment at the beginning of Cycle 2 of chemotherapy; weight was available for 656 (80%). By Cycles 3 and 4, weight was available for 448 (55%) and 384 (47%), respectively. From baseline to immediately prior to Cycle 2, 208 (32%) gained weight; 225 (34%) lost <2% of baseline weight; and 223 (34% of 656) lost 2% or more. Median survival from the beginning of Cycle 2 was 13.0, 10.9, and 6.9 months for patients with weight gain, weight loss of <2%, and weight loss of 2% or more, respectively. In multivariate analyses, adjusted for age, sex, performance score, type of treatment, and body mass index, weight loss of 2% or more was associated with poor overall survival compared with weight gain [hazard ratio (HR) = 1.66; 95% confidence interval (CI): 1.33-2.07; P < 0.001] and compared with weight loss of <2% (HR = 1.57; 95% CI: 1.27-1.95; P < 0.001). Although weight loss of <2% was not associated with poorer overall survival compared with weight gain, it was associated with poorer progression-free survival (HR = 1.24; 95% CI: 1.01-1.51; P = 0.036). Similar findings were observed in a separate 255-patient validation cohort. Conclusions Weight should be integrated into cancer cachexia trials because of its ease of frequent measurement and sustained prognostic association.

The Spectrum of Malnutrition/Cachexia/Sarcopenia in Oncology According to Different Cancer Types and Settings: A Narrative Review

“…Specific tumors, such as lung and pancreas present distinct gene expression profiles of cachexia-inducing factors that may explain why these cancer types are more prone to develop a wasting syndrome [52]. Cachexia is a strong prognostic marker of adverse clinical outcomes, as demonstrated by the observation that, at least in lung cancer, a weight loss ≥2% has been associated with poor overall and progression-free survival [53].…”

A multicenter, open‐label, single‐arm study of anamorelin (ONO‐7643) in patients with cancer cachexia and low body mass index

“…Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment 1 . Cancer cachexia diminishes the patient's physical function and reduces his or her quality of life and ability to tolerate chemotherapy, and this results in a poor prognosis 2‐7 …”

“…1 Cancer cachexia diminishes the patient's physical function and reduces his or her quality of life and ability to tolerate chemotherapy, and this results in a poor prognosis. [2][3][4][5][6][7] Although several societies have developed guidelines for managing cancer cachexia that mainly encompass nutritional support and pharmacotherapies for addressing symptoms, [8][9][10] no medications are explicitly indicated for treating cancer cachexia. These guidelines generally suggest corticosteroids and progestins.…”

“… 1 Cancer cachexia diminishes the patient's physical function and reduces his or her quality of life and ability to tolerate chemotherapy, and this results in a poor prognosis. 2 , 3 , 4 , 5 , 6 , 7 …”

Impact of cancer cachexia on the therapeutic outcome of combined chemoimmunotherapy in patients with non-small cell lung cancer: a retrospective study

“… 38 Previous studies summarizing data from the time when ICIs were not commercially available reported that weight loss during treatment is associated with shortening of PFS and OS. 39 , 40 In patients with NSCLC and PD-L1 ≥ 50%, BMI variations have been reported to be associated with clinical outcomes after pembrolizumab monotherapy. 41 The development of a treatment method to improve cancer cachexia is desired.…”