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Clinical Trial
. 2025 Jun;16(3):e13871.
doi: 10.1002/jcsm.13871.

A Randomized Trial of Nutrition and Exercise Treatment in Patients With Pancreatic and Non-Small Cell Lung Cancer (NEXTAC-TWO)

Shuichi Mitsunaga  1   2 , Tateaki Naito  3 , Hisao Imai  4   5 , Madoka Kimura  6 , Satoru Miura  7 , Hisashi Tanaka  8 , Takuro Mizukami  9   10 , Akira Imoto  11   12 , Chihiro Kondoh  13 , Hiroyuki Okuyama  14 , Makoto Ueno  15 , Shinsuke Shiotsu  16 , Toshimi Inano  17 , Haruka Chitose  18 , Noriatsu Tatematsu  19 , Taro Okayama  20 , Takako Mouri  21 , Miwa Sugiyama  22 , Katsuhiro Omae  23 , Takanori Kawabata  23 , Keita Mori  24 , Koichi Takayama  25
Affiliations
Clinical Trial

A Randomized Trial of Nutrition and Exercise Treatment in Patients With Pancreatic and Non-Small Cell Lung Cancer (NEXTAC-TWO)

Shuichi Mitsunaga et al. J Cachexia Sarcopenia Muscle. 2025 Jun.

Abstract

Background: In our previous study (NEXTAC-ONE), the Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) program (including home-based exercise and branched-chain amino acid-containing supplements combined with nutritional counselling) was shown to potentially prevent low muscle mass-related disability in elderly cancer patients. This randomized controlled trial (NEXTAC-TWO) was conducted to elucidate whether the NEXTAC program prolongs disability-free survival in elderly patients with advanced pancreatic or non-small cell lung cancer.

Methods: This open-label, multicentre, randomized phase II study was conducted at 15 Japanese hospitals. Patients aged ≥ 70 years, with pathologically proven advanced pancreatic or non-small cell lung cancer, who were scheduled to undergo systemic chemotherapy for treatment-naïve tumours were randomly assigned (1:1) to undergo observation or receive the NEXTAC program for 12 weeks. Randomization was performed by the minimization method, using performance status and types with cancer diagnosis and anticancer treatment as adjustment factors. The primary endpoint was disability-free survival (period from randomization to the date patients were evaluated as needing care or death due to any cause). Key secondary endpoints were change in weight, muscle mass, physical activity, nutritional assessment, safety and survival. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028801).

Results: From 2017 to 2019, 131 patients were enrolled and randomly assigned to NEXTAC (n = 66) or control arms (n = 65, median age 76.0 years). After randomization, two patients in the NEXTAC arm declined further participation. As a result, 64 patients (median age 75.5 years) received at least one session of the NEXTAC program. The completion rate of the planned exercise and nutrition consultation sessions was 98.4% in the NEXTAC arm. Of the 129 patients, 91 (71%) had a disability (44 in the NEXTAC arm; 47 in the control arm). In the primary analysis, median disability-free survival periods were 478 days (95% confidence interval [CI], 358-576) in the NEXTAC arm and 499 days in the control arm (95% CI, 363-604), with no significant differences between them (p = 0.884). The hazard ratio for disability-free survival in the NEXTAC arm compared with the control arm was 0.970 (95% CI 0.642-1.465). There were no differences in the secondary endpoints between the two arms.

Conclusions: The patients had good compliance with the 12-week NEXTAC program but failed to show significant improvements in disability-free survival as compared to observation alone. Further study on the progression of low muscle mass in the NEXTAC arm is needed.

Keywords: cancer cachexia; elderly; low muscle mass; multimodal intervention; non‐small cell lung cancer; pancreatic cancer.

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Conflict of interest statement

S. Mitsunaga reports grants from Ajinomoto, Ono Pharmaceutical and Pfizer Inc. outside the submitted work; lecture fees from Ono Pharmaceutical, Otsuka Pharmaceutical and Meiji Seika pharmaceutical outside the submitted work; and a patent for a biomarker using free plasma amino acids to predict sarcopenia outside the submitted work. T. Natio is an associated editor for The Journal of Cachexia, Sarcopenia and Muscle and reports a grant from Otsuka Pharmaceutical outside the submitted work; a lecture fee from Ono Pharmaceutical outside the submitted work; and advisory fees from Ono Pharmaceutical and Pfizer outside the submitted work. S. Miura reports a lecture fee from Ono Pharmaceutical outside the submitted work. H. Tanaka reports lecture fees from Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical, Boehringer‐Ingelheim, Eli Lilly, MSD, Takeda Pharmaceutical and Pfizer outside the submitted work. T. Mizukami reports a lecture fee from Ono Pharmaceutical outside the submitted work. C. Kondoh reports a lecture fee from Ono Pharmaceutical outside the submitted work. H. Okuyama reports a lecture fee from Otsuka Pharmaceutical outside the submitted work. M. Ueno reports a grant and a lecture fee from Ono Pharmaceutical outside the submitted work. H. Chitose reports lecture fees from Otsuka Pharmaceutical, Sanofi and Viatris outside the submitted work. K. Mori reports lecture fees from Chugai Pharmaceutical, Eli Lilly and Ono Pharmaceutical outside the submitted work. K. Takayama reports a grant from The Japan Agency for Medical Research and Development (AMED) under grant number JP18ck0106212 during the submitted work; grants from AstraZeneca, Chugai Pharmaceutical and Eli Lilly outside the submitted work; an advisory fee from AstraZeneca outside the submitted work; and lecture fees from AstraZeneca, Chugai Pharmaceutical, Boehringer‐Ingelheim, Eli Lilly, MSD‐Merck, Ono Pharmaceutical, Novartis, and Daiichi‐Sankyo outside the submitted work. No potential conflicts of interest were reported by the other authors.

Figures

FIGURE 1
FIGURE 1
Patient inclusion in the study. The NEXTAC program consisted of exercise and branched‐chain amino acid‐containing supplements combined with nutritional consultation for a 12‐week period.
FIGURE 2
FIGURE 2
Kaplan–Meier estimates of disability‐free survival in the 129 evaluable patients according to treatment arm. The vertical marks along the curves indicate censored data.
FIGURE 3
FIGURE 3
Kaplan–Meier estimates of overall survival (A) and progression‐free survival (B) in the 129 evaluable patients according to treatment arm. The vertical marks along the curves indicate censored data.
FIGURE 4
FIGURE 4
Forest plot of the treatment effect of disability‐free survival in subgroup analysis. The position of each square represents the point estimate of the treatment effect, and error bars represent 95% CIs. The sizes of the squares are proportional to the precision of the estimates. Tumour stage was evaluated using the TNM classification of malignant tumours, 8th edition. Cachexia was defined as weight loss of > 5% during the previous 6 months or of > 2% in patients with body mass index (BMI) < 20 kg/m2 or based on the presence of muscle depletion. Low muscle mass was defined based on lumbar skeletal muscle index cutoffs of < 43.0 cm2/m2 for men with a BMI < 25.0 kg/m2, < 53.0 cm2/m2 for men with a BMI ≥ 25.0 kg/m2 and < 41.0 cm2/m2 for women. ECOG‐PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio.
See this image and copyright information in PMC

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