metaEvidence - study list


	Study	study type RCT OBS RCT + OBS	Pathology	T1	T0	Patients	sample sizes	ROB	Results
metastatic/advanced - colorectal cancer (mCRC) metastatic/advanced - colorectal cancer (mCRC)
versus Standard of Care (SoC)
	atezolizumab plus cometinib
	Modul Cohort 4, 2023 European Journal of Cancer NCT02291289	RCT	metastatic/advanced - colorectal cancer (mCRC)	atezolizumab plus cobimetinib	fluoropyrimidine plus bevacizumab in 2- or 3-week treatment cycles depending on the fluoropyrimidine used	Patients 18 years of age or older with histologically confirmed, measurable, unresectable mCRC	65 / 34	some concern	inconclusive	inconclusive 44 % increase in progression or deaths (PFS) (PE) Cobimetinib plus atezolizumab had an unfavourable benefit:risk ratio in HER2‒/MSS/BRAFwt mCRC.
	atezolizumab plus SoC
	Modul Cohort 2, 2022 J Cancer Res Clin Oncol 2018;: ESMO Oct 2022 NCT02291289	RCT	metastatic/advanced - colorectal cancer (mCRC)	Atezolizumab plus control	FP (fluoropyrimidine) based chemotherapy plus bevacizumab	Patients 18 y and older with histologically confirmed, measurable, unresectable, previously untreated mCRC, an ECOG PS <= 2, and >=16 weeks of life expectancy at the time of study entry	297 / 148	low	inconclusive	inconclusive 8 % decrease in progression or deaths (PFS) (PE)
mCRC - 1st line (L1) metastatic/advanced - colorectal cancer (mCRC) mCRC - 1st line (L1)
versus Bevacizumab plus FOLFOXIRI
	atezolizumab plus FOLFOXIRI plus bevacizumab
	AtezoTRIBE, 2022 BMC Cancer 2020 Jul 22;20(1):683. The Lancet Onc. July 2022 ASCO May 2023 NCT03721653	RCT	mCRC - 1st line (L1)	atezolizumab plus FOLFOXIRI plus bevacizumab	FOLFOXIRI plus bevacizumab	Patients aged 18–75 years, with ECOG PS ≤2 if aged < 70 years, or ECOG PS 0 if aged 71–75 years	145 / 73	some concern	suggested	suggested 30 % decrease in progression or deaths (PFS) (PE) 1) The addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab is safe and improved progression-free survival in patients with previously untreated metastatic colorectal cancer2) Pts with IS IC-high and/or TMB high pMMR mCRC seem to derive a survival benefit from adding atezo to FOLFOXIRI/bev as upfront treatment.
versus Standard of Care (SoC)
	nivolumab plus SoC
	CheckMate 9X8, 2024 Journal of Clinical Oncology J Immunother Cancer. 2024 Mar 13;12(3):e008409 NCT03414983	RCT	mCRC - 1st line (L1)	nivolumab plus mFOLFOX6 plus bevacizumab	mFOLFOX6 plus bevacizumab	Patients aged at least 18 years with histologically confirmed mCRC not amenable to curative resection and no prior chemotherapy for metastatic disease	127 / 68	low	inconclusive	inconclusive 19 % decrease in progression or deaths (PFS) (PE) The CheckMate 9X8 trial investigating first-line nivolumab plus SOC versus SOC in patients with mCRC did not meet its primary endpoint of PFS by BICR. Nivolumab plus SOC showed numerically higher PFS rates after 12 months, a higher response rate, and more durable responses compared with SOC alone, with acceptable safety
	METIMMOX, 2024 ASCO May 2021 Br J Cancer 130, 1921–1928 (2024) OncoImmunology, 13(1). NCT03388190	RCT	mCRC - 1st line (L1)	nivolumab plus SOC	SOC	previously untreated, unresectable metastatic colorectal, MSS, no upper age limit,	38 / 38	some concern	no results	no results The investigational regimen did not improve the primary outcome for the intention-to-treat population but might beneﬁt small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer.
	pembrolizumab alone
	KEYNOTE-177, 2020 N Engl J Med. 2020 Dec 3;383(23):2207-2218. Lancet Oncol 2021 Apr 1;S1470-2045(21)00064-4. Lancet Oncol 2022; 23:659-670-. Cancer Sci 2023; 114:1026-1036-. NCT02563002	RCT	mCRC - 1st line (L1)	Pembrolizumab	chemotherapy FOLFIRI or FOLFOX plus targeted therapy	treatment-naïve U.S. patients with microsatellite instability-high (MSI-H) and/or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC)	153 / 154	some concern	conclusif	demonstrated 40 % decrease in progression or deaths (PFS) (PE) this study demonstrated a doubling in progression-free survival (PFS) with pembrolizumab versus standard chemotherapy in patients with newly diagnosed MSI-H mCRC leading to FDA approval for pembrolizumab in first line treatment of patients with unresectable or metastatic MSI-H/dMMR CRC
	durvalumab based treatment, Standard of Care (SoC)
	Columbia 1, 2024 ESMO December 2022 British Journal of Cancer NCT04068610	RCT	mCRC - 1st line (L1)	durvalumab plus ocleclumab plus SOC	SOC	patients ≥ 18 years in First line therapy of Metastatic Microsatellite-stable Colorectal Cancer with an ECOG of 0 or 1	26 / 26	low	inconclusive	inconclusive 80 % increase in objective responses (ORR),objective responses (ORR) (PE) Addition of Durvalumab plus Oleclumab to FOLFOX plus BEV (SoC) showed a moderate response increase without PFS benefit vs SoC alone. Safety was consistent with known safety profiles
mCRC - 2nd line (L2) metastatic/advanced - colorectal cancer (mCRC) mCRC - 2nd line (L2)
versus BSC
	durvalumab plus tremelimumab
	CO.26 study, 2020 JAMA Oncol 2020 Jun 1;6(6):831-838. NCT02870920	RCT	mCRC - 2nd line (L2)	durvalumab plus tremelimumab and BSC	BSC	Patients With Advanced Colorectal Adenocarcinoma Refractory to Standard Therapies	119 / 61	some concern	inconclusive	suggested 28 % decrease in deaths (OS) (PE)
versus capecitabine, placebo plus bevacizumab
	atezolizumab plus bevacizumab, capecitabine
	BACCI, 2022 JAMA Netw Open 2022; 5:e2149040-. NCT02873195	RCT	mCRC - 2nd line (L2)	capecitabine plus bevacizumab plus atezolizumab	capecitabine plus bevacizumab plus placebo	Patients 18 years and older with Refractory Metastatic Colorectal Cancer	82 / 46	low	inconclusive	inconclusive 27 % decrease in progression or deaths (PFS),progression or deaths (PFS) (PE) In this randomized clinical trial, the addition of atezolizumab to capecitabine and bevacizumab therapy provided limited (ie, not clinically meaningful) clinical benefit. Patients with MSS and proficient mismatch repair tumors and those without liver metastasis benefited more
versus regorafenib
	atezolizumab alone
	IMblaze-370 (A ; all population), 2019 Lancet Oncol. 2019; 20:849-861 NCT02788279	RCT	mCRC - 2nd line (L2)	atezolizumab monotherapy	regorafenib	patients with unresectable locally advanced or metastatic colorectal cancer and disease progression on or intolerance to at least two previous systemic chemotherapy regimens were enrolled.	90 / 90	some concern	inconclusive	inconclusive 0 % increase in deaths (OS) (PE)
	atezolizumab plus cometinib
	IMblaze-370 (AC ; all population), 2019 Lancet Oncol. 2019; 20:849-861 NCT02788279	RCT	mCRC - 2nd line (L2)	atezolizumab plus cometinib	regorafenib	patients with unresectable locally advanced or metastatic colorectal cancer with disease progression on or intolerance to at least two previous systemic chemotherapy regimens were enrolled.	183 / 90	some concern	inconclusive	inconclusive 0 % increase in deaths (OS) (PE)
versus Standard of Care (SoC)
	avelumab alone
	SAMCO-PRODIGE 54, 2023 Dig Liver Dis 2020 Dec 24;S1590-8658(20)31052-5. JAMA Oncol 2023 Oct NCT03186326	RCT	mCRC - 2nd line (L2)	avelumab	FOLFOX if FOLFIRI in first line or FOLFIRI if FOLFOX in first line or Investigator decision if FP in first line /- targeted therapy (panitumab cetuximab bevacizumab aflibercept), 1 treatment every 14 days	2nd Line Treatment in Patients With Colorectal Metastatic Cancer With Microsatellite Instability (dMMR/MSI mCRC) after first line treatment failure	61 / 61	high	inconclusive	no statistically significant result The SAMCO-PRODIGE 54 phase 2 randomized clinical trial showed, in patients with dMMR/MSI mCRC, better PFS and disease control duration with avelumab over standard second-line treatment, with a favorable safety profile.
	nivolumab plus ipilimumab
	CheckMate 8HW, 2024 ASCO ASCO NCT04008030	RCT	mCRC - 2nd line (L2)	nivolumab plus ipilimumab (Arm B)	SOC (ICC), chemo ± targeted therapies	Patients ≥ 18 years with Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC) recurrent or not amenable to surgery	171 / 84	NA	conclusif	demonstrated 79 % decrease in progression or deaths (PFS) (PE) suggested 79 % decrease in PFS (extension) NIVO plus IPI demonstrated superior PFS vs chemo in previously untreated pts with MSI-H/dMMR mCRC, Clinical benefit with 1L NIVO plus IPI vs chemo was maintained after subsequent therapy, as shown by improved PFS2 in pts with centrally confirmed MSI-H/dMMR mCRC

metastatic/advanced - colorectal cancer (mCRC) metastatic/advanced - colorectal cancer (mCRC)

mCRC - 1st line (L1) metastatic/advanced - colorectal cancer (mCRC) mCRC - 1st line (L1)

mCRC - 2nd line (L2) metastatic/advanced - colorectal cancer (mCRC) mCRC - 2nd line (L2)