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Review
. 2022 Jul;13(14):2064-2074.
doi: 10.1111/1759-7714.14529. Epub 2022 Jun 13.

Predicting the efficacy of first-line immunotherapy by combining cancer cachexia and tumor burden in advanced non-small cell lung cancer

Taichi Miyawaki  1   2 , Tateaki Naito  1 , Kosei Doshita  1 , Hiroaki Kodama  1 , Mikiko Mori  2 , Naoya Nishioka  1 , Yuko Iida  1 , Eriko Miyawaki  1 , Nobuaki Mamesaya  1 , Haruki Kobayashi  1 , Shota Omori  1 , Ryo Ko  1 , Kazushige Wakuda  1 , Akira Ono  1 , Hirotsugu Kenmotsu  1 , Haruyasu Murakami  1 , Keita Mori  3 , Hideyuki Harada  4 , Masahiro Endo  5 , Kazuhisa Takahashi  2 , Toshiaki Takahashi  1
Affiliations
Review

Predicting the efficacy of first-line immunotherapy by combining cancer cachexia and tumor burden in advanced non-small cell lung cancer

Taichi Miyawaki et al. Thorac Cancer. 2022 Jul.

Abstract

Background: Cancer cachexia and tumor burden predict efficacies of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy or pembrolizumab in non-small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden.

Methods: In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first-line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression-free survival (PFS) and overall survival (OS).

Results: A total of 157 patients were included in the present study (75 treated with PD-1/PD-L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD-L1 tumor proportion scores <50%, a total target lesion diameter ≥76 mm, and cancer cachexia were independently associated with poor PFS. Multivariate analysis for OS revealed that ≥4 metastases and cancer cachexia were significantly associated with poor OS. In the immune predictive model, the median PFS was 21.7 months in the low-risk group (N = 41); 7.6 in the medium-risk group (N = 64); and 3.0 in the high-risk group (N = 47). The median OS were not reached, 22.4 and 9.1 months respectively. Our immune predictive model was significantly associated with PFS (p < 0.001) and OS (p < 0.001).

Conclusion: We proposed the immune predictive model, including tumor burden and cancer cachexia, which may predict the efficacy and survival outcome of first-line immunotherapy in advanced NSCLC.

Keywords: cancer cachexia; immune checkpoint inhbitor; non-small cell lung cancer; predictive model; tumor burden.

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Conflict of interest statement

Dr Kobayashi reports personal fees from Eli Lilly K.K., Taiho Pharmaceutical, and AstraZeneca, outside the submitted work. Dr. Omori reports personal fees from Chugai Pharma‐ceutical Co., Ltd., Ono Pharmaceutical, AstraZeneca K.K., Boehringer Ingelheim, Taiho Pharmaceutical, and MSD, which are unrelated to the submitted study. Dr Ko reports grants and personal fees from Boehringer Ingelheim and AstraZeneca; personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, and Eli Lilly K.K. outside the submitted work. Dr Wakuda reports grants and personal fees from Chugai Pharmaceutical Co., Ltd.; personal fees from Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly K.K., Ono Pharmaceutical, and MSD; grants and personal fees from AstraZeneca; grants from Novartis and AbbVie, outside the submitted study. Dr Ono reports grants from Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharmaceutical Co., Ltd., and Novartis Pharma K.K., outside the submitted work. Dr Kenmotsu reports grants and personal fees from Chugai Pharmaceutical Co., Ltd.; personal fees from Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim, Eli Lilly K.K., Kyowa Hakko Kirin Co., Ltd., Bristol‐Myers Squibb, MSD; grants and personal fees from Novartis Pharma K.K., Daiichi‐Sankyo Co., Ltd., AstraZeneca K.K.; personal fees from Pfizer and Taiho Pharma, outside the submitted study. Dr Mamesaya reports personal fees from AstraZeneca K.K., Pfizer Japan, Inc., and Chugai Pharmaceutical Co., Ltd.; grants and personal fees from Boehringer Ingelheim (Ingelheim, Germany); personal fees from MSD K.K., Taiho Phar‐Maceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd., outside the submitted study. Dr Murakami reports personal fees from AstraZeneca K.K., Ono Pharmaceutical, Bris‐tol‐Myers Squibb Japan, Chugai Pharmaceutical Co., Ltd., Pfizer Inc. (New York, United States of America), Novartis Pharma K.K., Boehringer Ingelheim, Taiho Pharmaceutical, Eli Lilly K.K., and MSD, which are unrelated to the submitted work. Dr Harada reports personal fees from Daiichi‐Sankyo Pharmaceutical Co. while this study was performed as well as personal fees from Daiichi‐Sankyo Pharmaceutical Co., AstraZeneca K.K., Brain Labo Co., and Chugai Pharmaceutical Co. and grants from the Japan Agency for Medical Research and Development and the Na‐tional Cancer Center Research and Development Fund, which are unrelated to the submitted work. Dr Endo reports personal fees from Ono Pharmaceutical, AstraZeneca, Takeda Pharmaceutical Co., Ltd., and Daiichi‐Sankyo Co., Ltd., outside the submitted work. Dr Kazuhisa Takahashi reports grants and personal fees from AstraZeneca K.K., Pfizer Japan, Inc., Eli Lilly K.K., MSD, and Boehringer Ingelheim as well as grants from Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., GlaxoSmithKline Consumer Healthcare Japan K.K., Shionogi & Co., Ltd., and Novartis Pharma K.K., which are not related to the submitted work. Dr Toshiaki Takahashi reports grants and personal fees from AstraZeneca K.K., Pfizer Japan, Inc., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan, Inc., and Pfizer Japan, Inc.; and personal fees from Roche Diagnostics (Pleasanton, CA, United States of America) K.K., outside the submitted work. The remaining authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Study flowchart. ECOG, Eastern Cooperative Oncology Group; PD‐1, programmed death 1; PD‐L1, programmed death‐ligand 1.
FIGURE 2
FIGURE 2
(a) Correlation between sum of the longest diameters of the target lesions and number of metastatic lesions based on Spearman's rank correlation. (b) Correlation between rate of weight loss and number of metastatic lesions based on Spearman's rank correlation. (c) Correlation between rate of weight loss and sum of the longest diameters of the target lesions based on Spearman's rank correlation.
FIGURE 3
FIGURE 3
Factors of clinical immunopredictive score and classification of survival risk for immunopredictive model.
FIGURE 4
FIGURE 4
(a) Kaplan–Meier estimates of progression‐free survival among patients in low‐, medium‐, and high‐risk groups. (b) Kaplan–Meier estimates of overall survival among patients in low‐, medium‐, and high‐risk groups.
FIGURE 5
FIGURE 5
(a) Kaplan–Meier estimates of progression‐free survival among patients in low‐risk, medium‐risk, and high‐risk groups in patients treated with PD‐1/PD‐L1 inhibitors plus chemotherapy. (b) Kaplan–Meier estimates of overall survival among patients in low‐, medium‐, and high‐risk groups in patients treated with PD‐1/PD‐L1 inhibitors plus chemotherapy.
FIGURE 6
FIGURE 6
(a) Kaplan–Meier estimates of progression‐free survival among patients in low‐, medium‐, and high‐risk groups in patients treated with pembrolizumab monotherapy. (b) Kaplan–Meier estimates of overall survival among patients in low‐, medium‐, and high‐risk groups in patients treated with pembrolizumab monotherapy.
See this image and copyright information in PMC

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