Impact of Cachexia and First‐Line Systemic Therapy for Previously Untreated Advanced Non‐Small Cell Lung Cancer: NEJ050A
Authors: Miura Keita , Shukuya Takehito , Furuya Naoki , Morita Ryo , Kisohara Akira , Mouri Atsuto , Watanabe Satoshi , Tanaka Hisashi , Hirata Aya , Hakozaki Taiki , Hamai Kosuke , Matsumoto Naoko , Watanabe Kana , Ashinuma Hironori , Miyauchi Eisaku , Sugano Koji , Hosokawa Shinobu , Amano Koji , Morita Satoshi , Kobayashi Kunihiko , Maemonodo Makoto , Takahashi Kazuhisa 
Published: October 2024

Background

Cancer cachexia complicates advanced non‐small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first‐line systemic therapy.

Methods

We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0–2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first‐line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first‐line systemic therapy.

Results

A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0–2 who were initiated on first‐line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first‐line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy‐associated emesis affecting early appetite‐related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: −3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (−1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression‐free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003).

Conclusions

Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite‐related QOL trends vary based on the type of first‐line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.