CRC: FIRE-3 trial

Abbreviations

No EU-CTR

  • FIRE-3 references
    2020-11-06
    Volker Heinemann

    BJC

    FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer: final survival and per-protocol analysis of FIRE-3
Investigated (inv)
Comparator (comp)

FOLFIRI+CETU

FOLFIRI+BEVA

169

183

Phase:

3

Randomisation:

Open label

Primary tumour:

CRC

Subtype (biomarker):

KRAS WT

Stage:

meta

Line of therapy:

L1

Primary
FOLFIRI+CETU
FOLFIRI+BEVA
HR
p
ORR
77%
65%
0.54 (0.34-0.86)
0.014
Secondaries
FOLFIRI+CETU
FOLFIRI+BEVA
HR
p
OS RAS WT
31 mo
26 mo
0.76
0.012
OS
33 mo
26 mo
0.75
0.011
PFS RAS WT
10.3 mo
10.4 mo
0.96
0.71
Median depth of response
49%
32%
<0.0001
(all grades, %)
FOLFIRI+CETU
FOLFIRI+BEVA
p
Any AE gr.≥3
64
51
NA
Withdrawn due to treatment
15
8
NA
Serious adverse events
17
19
NA
Deaths associated with SAEs
1.5
0.0
NA
Diarrhoea
60.8
1.5
NA
Mucositis/stomatitis
42.7
90.0
NA
Vomiting
24.1
34.3
NA
Bleeding (respiratory tractdc-comma GIdc-comma GU)
22.6
29.9
NA
Liver toxicity
68.8
59.7
NA
Electrolyte imbalance
64.8
42.8
NA
Nausea
49.7
65.7
NA
Hypertension
24.6
37.3
NA
Arrhythmias
6.5
10.0
NA
Oedema
15.6
10.4
NA
  • Inclusion
  • Exclusion

- KRAS-Wildtype statusdc-return- Histologically confirmed adenocarcinoma of the colon or rectum; - Stage IV disease.dc-return- ECOG 0-2; - Patients considered suitable for application of chemotherapy; - Age 18 - 75 years - In- or outpatient treatment - Estimated life expectancy > 3 months; - Measurable index lesion according to RECIST criteria. Evaluation of tumor manifestations ≤ 2 weeks prior to treatment start; - Effective contraception; - Adequate hematologic function: leukocytes ≥ 3000/µl, neutrophils ≥ 1500/µl, platelets ≥ 100.000/µ, and hemoglobin ≥ 9g/dl. - Bilirubin ≤ 1,5x upper limit of normal (ULN); - ALAT and ASAT ≤ 2,5x ULN, in case of liver metastases ≤ 5x ULN; - Serum creatinine ≤ 1,5x ULN; - No operations within 4 weeks prior to treatment start. No cytologic biopsies within 1 week prior to treatment start.

- KRAS-Mutation of the tumordc-return- Prior treatment directed against the epidermal growth factor receptor (EGFR).dc-return- Prior treatment with bevacizumab.dc-return- Prior chemotherapy for colorectal cancer, except for adjuvant chemotherapy dating back > 6 months prior to study entry.dc-return- Experimental medical treatment within 30 days prior to study entry.dc-return- Known hypersensitivity reaction to any study medication.dc-return- Pregnant or breast feeding women (pregnancy needs to be excluded by testing of beta-HCG).dc-return- Known or suspected cerebral metastases.dc-return- Clinically significant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia.dc-return- Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhea.dc-return- Symptomatic peritoneal carcinosis.dc-return- Severe chronic wounds, ulcera or bone fracture.dc-return- Uncontrolled hypertension.dc-return

Characteristics
FOLFIRI+CETU
FOLFIRI+BEVA
Age & sex
Median agedc-comma yr (range)
64 (41–76)
64 (31–76)
> 65 yrdc-comma %
48
48
Femaledc-comma %
26
34
ECOG performance statusdc-comma %
0
54
54
1
44
44
2
2
2
Site of primary tumourdc-comma %
Colon
60
63
Rectum
36
34
Colon & rectum
4
4
Primary tumour sidedc-comma %
Left (hindgut)
79
74
Right (midgut)
19
25
Both or unknown
2
1
No. of metastatic sitesdc-comma %
1
42
41
2
33
34
≥ 3
24
24
Unknown
1
1
Metastatic sitesdc-comma %
Liver only
36
31
Lung only
3
6
Prior therapydc-comma %
Primary tumour resection
84
88
Adjuvant chemotherapy
19
19
Ad-hoc:
no.pts inv.
no.pts comp.
FOLFIRI+CETU
FOLFIRI+BEVA
HR
p
Early tumour shrinkage (ETS)
105
85
70%
50%
0.43 (0.27-0.68)
0.0004
ORR left-sided
108
92
79%
68%
0.56 (0.32-0.97)
0.041
ORR right-sided
20
25
67%
56%
0.47
  • ORR
analisys of ORR
FOLFIRI+CETU
FOLFIRI+BEVA
HR (95% CI)
analisys of
FOLFIRI+CETU
FOLFIRI+BEVA
HR (95% CI)