Review and prospect of neoadjuvant chemoradiotherapy combined with immunotherapy in locally advanced rectal cancer

doi:10.16139/j.1007-9610.2024.03.07

Abstract

Abstract:

For locally advanced rectal cancer (LARC), the standard treatment of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) leaded to limited tumor regression grade and organ preservation rate, and didn’t decrease the rate of distant metastasis. Radiotherapy can promote the immune response and has good synergistic effect with immunotherapy, which is likely to overcome the treatment difficulty of the microsatellite stable(MSS) colorectal cancer. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. Most of them have achieved promising complete response rates, providing new treatment options for preservation of organ functions in mid-low MSS LARC. Large-scale randomized controlled trials are needed in the future to validate these findings and explore the benefit of organ preservation and long-term survival. In addition, studies are still needed on the optimal combination patterns of radiotherapy and immunotherapy and the precise efficacy evaluation, etc.

Key words: Locally advanced rectal cancer(LARC), Neoadjuvant chemoradiotherapy, Immunotherapy, Complete response, Organ preservation

CLC Number:

R735.37

WANG Yaqi, XIA Fan, ZHANG Zhen. Review and prospect of neoadjuvant chemoradiotherapy combined with immunotherapy in locally advanced rectal cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(03): 220-229.

Figures/Tables 2

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类别	名称/NCT编号	年份	国家地区	期别	样本量	病人特征	研究设计	CR率(%)
长程放化疗序贯免疫治疗	VOLTAGE-A^[18] NCT02948348	2019	日本	Ⅰb	37	Ⅲ期 23%	LCRT+Nivo×5	30
	NSABP FR-2^[19] NCT03102047	2021	美国	Ⅱ	45	Ⅲ期 89%	LCRT+Durva×4	53
	PANDORA^[20] NCT04083365	2021	意大利	Ⅱ	55	T3-4 95%; N+ 79%	LCRT+Nivo×3	32.7
长程放化疗同期免疫治疗	AVANA^[21] NCT03854799	2021	意大利	Ⅱ	101	Ⅲ期 94%	LCRT/Avelu×6	23
	R-IMMUNE^[22] NCT03127007	2023	北美	Ⅰb/Ⅱ	37	Ⅲ期 84%	LCRT/Atezo×4	27
	NECTAR^[23] NCT04911517	2024	中国北京	Ⅱ	50	T3-4 92%; N+ 64%	LCRT/Tisleli×3	40
长程放化疗联合化疗免疫	NRG-GI002^[24] NCT02921256	2021	美国	Ⅱ	95	高危T3-4/N+	FOLFOX×8+(LCRT+Pembro×6）	45
	长海研究^[25] ChiCTR2100042785	2022	中国上海	Ⅱ	23	T2-T3; N0 69%	LCRT/Sintili×2+(CAPOX×6+ Sintili×2)	52.2
	PKUCH 04^[26] NCT04340401	2022	中国北京	Ⅱ	25	N2 76%; MRF+56%	(CAPOX+ Camreli)×3+LCRT+CAPOX×2	49.3
	DUREC^[27] NCT04293419	2023	西班牙	Ⅱ	61	T3-4/N+	FOLFOX×6+Durva×6+LCRT	39
	STARS-RC03^[28] NCT04906044	2023	中国吉林	Ⅱ	30	T3-4/N+	TNT/Sintili	55
短程放疗序贯化疗免疫	Averectal^[31] NCT03503630	2021	欧洲	Ⅱ	40	Ⅲ期 91%	SCRT+(FOLFOX+Avelu)×6	37.5
	武汉协和Ⅱ期^[32] NCT04231552	2021	中国湖北	Ⅱ	30	高危T3-4/N+	SCRT+(CAPOX+Camreli)×2	46
	UNION^[33] NCT04928807	2023	中国湖北	Ⅲ	231	T3-4/N+	Arm1: SCRT+(CAPOX+Camreli)×2 Arm2: LCRT+CAPOX×2	39.8 vs. 15.3
	TORCH^[34] NCT04518280	2023	中国上海	Ⅱ	130	T3-4/N+	Arm1: SCRT+(CAPOX+Toripali)×6 Arm2: (CAPOX+Toripali)×2+SCRT+(CAPOX+Toripali)×4	57.4 vs. 54.0
	PRECAM^[35] NCT05216653	2023	中国浙江	Ⅱ	32	T3-4/N+	SCRT+ CAPOX×2/Envafo (qw)×6	66.7

类别	名称/NCT编号	年份	国家	期别	样本量	患者特征	研究设计	CR
长程放化疗序贯免疫治疗	TIMENT-R NCT05507112	2022	中国北京	Ⅱ	100	T3-4/N+	Arm1: LCRT+8-12w后Tisleli×3+TME Arm2: LCRT+8-12w后TME	pCR
长程放化疗序贯免疫治疗	Ave-Rec NCT03299660	2023	澳大利亚	Ⅱ	37	T3b-4/N1-2	LCRT+Avelu×4	pCR
长程放化疗同期免疫治疗	北京友谊Ⅲ期 NCT05245474	2023	中国北京	Ⅲ	186	cT3-4aN0M0 cT1- 4aN1-2M0	Arm1: LCRT/Tisleli×3 Arm2: LCRT+Tisleli×3 Arm3: LCRT	pCR
长程放化疗同期免疫治疗	CHINOREC NCT04124601	2022	奥地利	Ⅱ	80	T3-4/N+	LCRT/(Ipili×1+Nivo×3)	AEs, mrTRG, pTRG
长程放化疗联合化疗免疫	中山肿瘤研究 NCT04304209	2019	中国广州	Ⅱ	134	T3-4/N+	Arm1 ((/Sintili+CAPOX)×4+50Gy)评估后 ①+ TME/WW + CAPOX×4 ②+ CAPOX×4 + TME/WW Arm 2 pMMR:CAPOX×4+50Gy评估后 ①+ TME/WW + CAPOX×4 ②+ CAPOX×4 + TME/WW	CR
长程放化疗联合化疗免疫	CHOICE Ⅱ NCT05215379	2022	中国上海	Ⅱ-Ⅲ		距肛≤5cm T1-3aN0-1	Arm1: LCRT+CAPOX×2 Arm2: LCRT/Sintili×2+(CAPOX+ Sintili)×2	cCR
短程放疗序贯化疗免疫	STELLAR Ⅱ NCT05484024	2023	中国北京	Ⅲ	588	T3-4/N+	Arm1: SCRT + (CAPOX×4/FOLFOX×6)//Sintili×4 Arm2: SCRT + CAPOX×4/FOLFOX×6	CR
	浙江肿瘤 NCT04663763	2023	中国浙江	Ⅱ	40	T3-4/N+	SCRT + (CAPOX+Sintili)×4	pCR
	N-PRC NCT05576480	2023	中国上海	Ⅱ	55	T3-4/N+	(SCRT+Penpuli d6/7)+(CAPOX+Penpuli)×4	pCR
	PRECAM-R NCT05752136	2023	中国浙江	Ⅱ	32	T3-4/N+	Arm1 SCRT+CAPOX×2 Arm2 SCRT+ CAPOX×2/Envafo (qw)×6	pCR
长程vs.短程放疗序贯化疗免疫	PRIME-RT NCT04621370	2020	英国	Ⅱ	48	cT3b+, N+, EMVI+ or low rectal tumors	Arm1: (SCRT+FOLFOX×6)/Durva Arm2: (LCRT+FOLFOX×4)/Durva	CR