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. 2024 Feb 20;5(4):100655.
doi: 10.1016/j.jtocrr.2024.100655. eCollection 2024 Apr.

Immunotherapy With Radiotherapy for Brain Metastases in Patients With NSCLC: NEJ060

Takehiro Tozuka  1 , Yuji Minegishi  2 , Ou Yamaguchi  3 , Kana Watanabe  4 , Yukihiro Toi  5 , Ryota Saito  6 , Yoshiaki Nagai  7 , Yosuke Tamura  8 , Tetsuaki Shoji  9 , Haruka Odagiri  10 , Noriyuki Ebi  11 , Kosuke Sakai  12 , Nobuhiro Kanaji  13 , Makoto Izumi  14 , Sayo Soda  15 , Satoshi Watanabe  16 , Satoshi Morita  17 , Kunihiko Kobayashi  3 , Masahiro Seike  1
Affiliations

Immunotherapy With Radiotherapy for Brain Metastases in Patients With NSCLC: NEJ060

Takehiro Tozuka et al. JTO Clin Res Rep. .

Abstract

Introduction: Immune checkpoint inhibitor (ICI)-based treatment has become standard treatment for patients with advanced NSCLC. We aimed to determine the survival benefit of upfront radiotherapy for brain metastases (BMs) in patients with NSCLC who received ICI alone (ICI-alone) or with chemotherapy (ICI-chemo).

Methods: This study included consecutive patients with NSCLC having BMs who received ICI alone or ICI-chemo at 50 institutes between February 2017 and September 2021. The presence of BMs was confirmed by imaging before treatment. Treatment outcomes were compared between patients who did and did not receive upfront radiotherapy for BMs. Potential confounding factors were adjusted between the groups through inverse probability treatment weighting (IPTW) analysis and overlap weighting (OW) analysis with propensity scores.

Results: Patients were grouped as ICI-alone cohort, 224 patients (upfront-radiotherapy group, 135 patients; no-radiotherapy group, 89 patients) and ICI-chemo cohort, 367 patients (upfront-radiotherapy group, 212 patients; no-radiotherapy group, 155 patients). In the ICI-alone cohort, the overall survival of the upfront-radiotherapy group was significantly longer than that of the no-radiotherapy group (IPTW-adjusted hazards ratio [HR] = 0.45 [95% confidence interval [CI]: 0.29-0.72], OW-adjusted HR = 0.52 [95% CI: 0.35-0.77]). In contrast, in the ICI-chemo cohort, the OS of the upfront-radiotherapy group was not significantly different from that of the no-radiotherapy group (IPTW-adjusted HR = 1.02 [95% CI: 0.70-1.48], OW-adjusted HR = 0.93 [95% CI: 0.65-1.33]).

Conclusions: Upfront radiotherapy for BMs was associated with longer overall survival in patients with NSCLC who received ICI alone; however, it did not exhibit survival benefits in the patients who received ICI-chemo.

Keywords: Brain metastases; Immunotherapy; Non–small cell lung cancer; Radiotherapy.

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Conflict of interest statement

Dr. Tozuka has received honoraria from Chugai Pharmaceutical and AstraZeneca. Dr. Minegishi has received honoraria from AstraZeneca, Boehringer Ingelheim Japan, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Eisai, Bristol-Myers Squibb, Daiichi-Sankyo, Nippon Kayaku, Takeda Pharmaceutical, and GlaxoSmithKline. Dr. Yamaguchi has received honoraria from Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., and Chugai Pharmaceutical Co. Ltd. Dr. Toi has received honoraria from Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., AstraZeneca Plc., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Pfizer Inc., and Kyowa Kirin Co., Ltd. Dr. Tamura has received honoraria from Merck Sharp & Dohme (Merck & Co., Inc.), Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Ono Pharmaceutical Co., Ltd. Dr. Sakai has received grants from Eli Lilly Japan K.K.; and has received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., and ThermoFisher Scientific K.K. Dr. Watanabe has received funding from Bristol-Myers Squibb K.K. and 10.13039/501100013170Ono Pharmaceutical Co., Ltd.; has received grants from Boehringer Ingelheim and 10.13039/100018046Nippon Kayaku; and has received honoraria from Eli Lilly, Novartis Pharma, Chugai Pharma, Bristol-Myers, Ono Pharmaceutical, Daiichi-Sankyo, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Kirin, Merck, Takeda Pharmaceutical, Celltrion, and AstraZeneca. Dr. Morita has received honoraria from AstraZeneca K.K, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Merck Sharp & Dohme K.K., Pfizer Japan Inc., and Taiho Pharmaceutical Co., Ltd. Dr. Kobayashi has received honoraria from AstraZeneca, Daiichi-Sankyo Pharmaceutical Co., and Takeda Pharmaceutical Co.; and is the Board Chairman in NPO North East Japan Study Group. Dr. Seike has received honoraria from AstraZeneca, Merck Sharp & Dohme K.K, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo Company, Merck Biopharma, and Amgen Inc.; and has received research funding from 10.13039/100009954Taiho Pharmaceutical, 10.13039/100010795Chugai Pharmaceutical, Eli Lilly, 10.13039/100017346Nippon Boehringer Ingelheim, Nippon Kayaku and 10.13039/501100004095Kyowa Hakko Kirin. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient selection flowchart. BM, brain metastasis; ICI, immune checkpoint inhibitor; RT, radiotherapy.
Figure 2
Figure 2
OS curves to compare the upfront-RT and no-RT groups,. IPTW-adjusted Kaplan-Meier curves: (A) ICI-alone cohort, (B) ICI-chemo cohort. OW-adjusted Kaplan-Meier curves: (C) ICI-alone cohort and (D) ICI-chemo cohort. ICI, immune checkpoint inhibitor; ICI-chemo, ICI plus chemotherapy; IPTW, inverse probability treatment weighting; OS, overall survival; OW, overlap weighting; RT, radiotherapy.
Figure 3
Figure 3
PFS curves to compare the upfront-RT and no-RT groups. IPTW-adjusted Kaplan-Meier curves: (A) ICI-alone cohort, (B) ICI-chemo cohort. OW-adjusted Kaplan-Meier curves: (C) ICI-alone cohort. (D) ICI-chemo cohort. ICI, immune checkpoint inhibitor; ICI-chemo, ICI plus chemotherapy; IPTW, inverse probability treatment weighting; OW, overlap weighting; PFS, progression-free survival; RT, radiotherapy.
Figure 4
Figure 4
CNS-PFS curves to compare the upfront-RT and no-RT groups. IPTW-adjusted Kaplan-Meier curves: (A) ICI-alone cohort, (B) ICI-chemo cohort. OW-adjusted Kaplan-Meier curves: (C) ICI-alone cohort. (D) ICI-chemo cohort. CNS-PFS, central nervous system progression-free survival; ICI, immune checkpoint inhibitor; ICI-chemo, ICI plus chemotherapy; IPTW, inverse probability treatment weighting; OW, overlap weighting; RT, radiotherapy.
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