Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study

Shoshihara, Nao; Matsumoto, Kinnosuke; Shiroyama, Takayuki; Komuta, Kiyohide; Miyazaki, Akito; Tamiya, Motohiro; Tsukaguchi, Akihiro; Tamiya, Akihiro; Kuge, Tomoki; Mihashi, Yasuhiro; Mori, Masahide; Yamauchi, Keijiro; Suzuki, Hidekazu; Kinehara, Yuhei; Machiyama, Hirotomo; Tanaka, Satoshi; Niki, Toshie; Kato, Soichiro; Nishikawa, Yuki; Osa, Akio; Azuma, Kouji; Takeda, Yoshito; Kumanogoh, Atsushi

doi:https://doi.org/10.1016/j.lungcan.2025.108835

Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study

Shoshihara, Nao; Matsumoto, Kinnosuke; Shiroyama, Takayuki et al.

Lung Cancer, 2025, 210, 108835

アクセス数:228件（2026-02-16 10:17 集計）

固定URL: https://hdl.handle.net/11094/103527

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タイトル	Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study
著者	著者名 Shoshihara, Nao
	ORCID 0000-0002-4930-6997 0000-0002-4930-6997 researchmap permalink kinnosuke.matsumoto kinnosuke.matsumoto Scopus Author ID 57215005043 57215005043 著者名 Matsumoto, Kinnosuke
	NRID 1000060860062 1000060860062 researchmap permalink shiroyama_t shiroyama_t Scopus Author ID 36476578400 36476578400 著者名 Shiroyama, Takayuki
	著者名 Komuta, Kiyohide
	著者名 Miyazaki, Akito
	著者名 Tamiya, Motohiro
	著者名 Tsukaguchi, Akihiro
	著者名 Tamiya, Akihiro
	ORCID 0000-0002-9787-1659 0000-0002-9787-1659 Scopus Author ID 57218792514 57218792514 著者名 Kuge, Tomoki
	著者名 Mihashi, Yasuhiro
	著者名 Mori, Masahide
	著者名 Yamauchi, Keijiro
	著者名 Suzuki, Hidekazu
	著者名 Kinehara, Yuhei
	著者名 Machiyama, Hirotomo
	著者名 Tanaka, Satoshi
	著者名 Niki, Toshie
	著者名 Kato, Soichiro
	著者名 Nishikawa, Yuki
	NRID 1000020751390 1000020751390 著者名 Osa, Akio
	著者名 Azuma, Kouji
	NRID 1000040452388 1000040452388 researchmap permalink yoshi10 yoshi10 Scopus Author ID 7404001848 7404001848 著者名 Takeda, Yoshito
	NRID 1000010294125 1000010294125 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 著者名 Kumanogoh, Atsushi
キーワード等	Chemotherapy
	Comparison
	Long-term
	Monotherapy
	Pembrolizumab
内容	Shoshihara N., Matsumoto K., Shiroyama T., et al. Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study. Lung Cancer 210, 108835 (2025); https://doi.org/10.1016/j.lungcan.2025.108835.
抄録	Background: Pembrolizumab is currently used as a first-line therapy for EGFR- and ALK-negative advanced non-small cell lung cancer (NSCLC). However, whether pembrolizumab alone (P-mono) or combined with platinum chemotherapy (P-combo) provides superior long-term benefit remains unclear. Methods: We retrospectively analyzed 392 patients with PD-L1 TPS ≥ 1 % treated first-line with P-mono (n = 194) or P-combo (n = 198) between 2019 and 2021. Propensity-score matching across 13 baseline variables yielded two well-balanced cohorts of 97 patients each, with a median follow-ups of 42.8 and 44.1 months, respectively. Results: P-combo prolonged overall survival (OS) (median 31.8 vs 20.7 months; hazard ratio [HR] 0.67, 95 % confidence interval [CI] 0.46–0.96) and progression-free survival (12.5 vs 7.0 months; HR 0.59, 95 %CI 0.43–0.81). The 3- and 4-year OS rates were 49.8 % and 42.7 %, respectively, with P-combo, compared with 28.1 % and 22.3 % with P-mono. The 48-month restricted mean survival time also favored P-combo (p = 0.039). Additionally, greater benefits were observed among patients aged < 75 years, with ECOG performance status 0–1, PD-L1 TPS 1–49 %, and those using proton-pump inhibitors. Grade ≥ 3 treatment-related adverse events (TRAEs) were more frequent with P-combo (35 % vs 20 %, p = 0.024). However, treatment-related deaths (2 % each) and pneumonitis incidence and severity were comparable; cumulative toxicity curves plateaued after 3 years. Conclusions: These findings suggest that P-combo showed a durable survival advantage over monotherapy and acceptable TRAEs in patients with PD-L1–positive NSCLC, identifying clinical subgroups most likely to benefit. Prospective randomized trials are warranted to validate these observations and guide optimal first-line treatment strategies.
出版者	Elsevier Ireland Ltd
収録物名	Lung Cancer
巻(号)	210
ページ	108835
刊行年月	2025-11-10
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103527
PISSN	01695002
eISSN	18728332
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.lungcan.2025.108835
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Lung Cancer. 2025, 210, p. 108835
DC.title	Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study
DC.creator	Shoshihara, Nao
	Matsumoto, Kinnosuke
	Shiroyama, Takayuki
	Komuta, Kiyohide
	Miyazaki, Akito
	Tamiya, Motohiro
	Tsukaguchi, Akihiro
	Tamiya, Akihiro
	Kuge, Tomoki
	Mihashi, Yasuhiro
	Mori, Masahide
	Yamauchi, Keijiro
	Suzuki, Hidekazu
	Kinehara, Yuhei
	Machiyama, Hirotomo
	Tanaka, Satoshi
	Niki, Toshie
	Kato, Soichiro
	Nishikawa, Yuki
	Osa, Akio
	Azuma, Kouji
	Takeda, Yoshito
	Kumanogoh, Atsushi
DC.publisher	Elsevier Ireland Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-11-10
DC.identifier	https://doi.org/10.1016/j.lungcan.2025.108835
DC.subject	Chemotherapy
	Comparison
	Long-term
	Monotherapy
	Pembrolizumab
DC.description	Shoshihara N., Matsumoto K., Shiroyama T., et al. Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study. Lung Cancer 210, 108835 (2025); https://doi.org/10.1016/j.lungcan.2025.108835.
DCTERMS.abstract	Background: Pembrolizumab is currently used as a first-line therapy for EGFR- and ALK-negative advanced non-small cell lung cancer (NSCLC). However, whether pembrolizumab alone (P-mono) or combined with platinum chemotherapy (P-combo) provides superior long-term benefit remains unclear. Methods: We retrospectively analyzed 392 patients with PD-L1 TPS ≥ 1 % treated first-line with P-mono (n = 194) or P-combo (n = 198) between 2019 and 2021. Propensity-score matching across 13 baseline variables yielded two well-balanced cohorts of 97 patients each, with a median follow-ups of 42.8 and 44.1 months, respectively. Results: P-combo prolonged overall survival (OS) (median 31.8 vs 20.7 months; hazard ratio [HR] 0.67, 95 % confidence interval [CI] 0.46–0.96) and progression-free survival (12.5 vs 7.0 months; HR 0.59, 95 %CI 0.43–0.81). The 3- and 4-year OS rates were 49.8 % and 42.7 %, respectively, with P-combo, compared with 28.1 % and 22.3 % with P-mono. The 48-month restricted mean survival time also favored P-combo (p = 0.039). Additionally, greater benefits were observed among patients aged < 75 years, with ECOG performance status 0–1, PD-L1 TPS 1–49 %, and those using proton-pump inhibitors. Grade ≥ 3 treatment-related adverse events (TRAEs) were more frequent with P-combo (35 % vs 20 %, p = 0.024). However, treatment-related deaths (2 % each) and pneumonitis incidence and severity were comparable; cumulative toxicity curves plateaued after 3 years. Conclusions: These findings suggest that P-combo showed a durable survival advantage over monotherapy and acceptable TRAEs in patients with PD-L1–positive NSCLC, identifying clinical subgroups most likely to benefit. Prospective randomized trials are warranted to validate these observations and guide optimal first-line treatment strategies.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103527
citation_title	Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study
citation_author	Shoshihara, Nao
	Matsumoto, Kinnosuke
	Shiroyama, Takayuki
	Komuta, Kiyohide
	Miyazaki, Akito
	Tamiya, Motohiro
	Tsukaguchi, Akihiro
	Tamiya, Akihiro
	Kuge, Tomoki
	Mihashi, Yasuhiro
	Mori, Masahide
	Yamauchi, Keijiro
	Suzuki, Hidekazu
	Kinehara, Yuhei
	Machiyama, Hirotomo
	Tanaka, Satoshi
	Niki, Toshie
	Kato, Soichiro
	Nishikawa, Yuki
	Osa, Akio
	Azuma, Kouji
	Takeda, Yoshito
	Kumanogoh, Atsushi
citation_publisher	Elsevier Ireland Ltd
citation_language	英語
citation_date	2025-11-10
citation_journal_title	Lung Cancer
citation_volume	210
citation_firstpage	108835
citation_doi	https://doi.org/10.1016/j.lungcan.2025.108835
citation_public_url	https://hdl.handle.net/11094/103527

Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study

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