Age-dependent differences in first-line chemotherapy in patients with metastatic colorectal cancer: the DISCO study

Figures & data

Figure 1. Patient selection for the DISCO study.

Table 1. Baseline characteristics for all treated and non-treated patients.

Variable	Category	Age 50–69 years		Age 70–89 years		p
		N = 338	%	N = 316	%
Age^a	Years	62 (50–69)		76 (70–89)		<.001
Body Mass Index^a	kg/m^2	24.3 (13.2–46.2)		23.8 (14.5–38.2)		.15
Sex	Men	181	54	169	54	1.000
	Women	157	46	147	46
Performance status	0	215	62	132	42	<.001
	1	73	22	105	33
	2+	50	15	79	25
Charlson comorbidity score	0	212	63	167	53	.021
	1–2	107	32	119	38
	3+	19	5.6	30	9.5
No. of drugs	0	94	28	37	12	<.001
	1–3	134	40	131	42
	4–5	56	17	65	21
	6–7	33	9.8	57	18
	8+	21	6.2	26	8.2
Civil status	Single	89	27	111	36	.017
	Living together	249	73	205	64
Primary localization of tumor	Right	100	30	117	37	.042
	Left	125	37	116	37
	Rectum	108	32	76	24
	Unknown	5	1.5	7	2.2
KRAS analyses	KRAS analyzed	297	88	220	70	<.001
	Missing	41	12	96	30
KRAS status	Mutation	134	45	104	47	.69
	No mutation	163	55	116	53
Disease at time of diagnosis	Synchronous	220	65	222	70	.35
	Recurrence	114	34	90	29
	Unresectable	4	1.2	4	1.3
Previous adjuvant chemotherapy	Yes	105	31	44	14	<.001
	No	233	69	272	86
Treatment	Yes	303	90	254	80	.001
	No	35	10	62	20
Start dose	Standard dose	230	68	102	32	<.001
	Reduced dose	68	20	150	48
	Unknown	40	12	64	20
Hemoglobin^a	mmol/L	8.00 (4.40–10.40)		7.30 (4.00–10.10)		<.001
Leucocytes ^a	10^9/L	7.30 (1.40–28.30)		7.80 (0.7–119.00)		.033
LDH^a	U/L	209 (87–3220)		206 (88–5720)		.94
CEA^a	μg/L	12 (1–7950)		19 (1–3670)		.12

^a Median (range).

Table 2. Association between baseline characteristics, treatment, and outcomes.

	PFS		All-cause mortality		CRC^c
	HR (95% CI)		HR (95% CI)		HR (95% CI)
All treated patients, N = 557	Unadjusted	Adjusted^a	Unadjusted	Adjusted^a	Unadjusted	Adjusted^a
Baseline characteristics for treated patients associated with outcomes
Age ≥70 years	1.32 (1.11–1.56)	1.16 (0.97–1.39)	1.67 (1.40–2.00)	1.48 (1.23–1.78)	1.51 (1.24–1.83)	1.36 (1.11–1.66)
BMI <18.5	1.51 (1.09–2.10)	1.36 (0.97–1.91)	1.43 (1.02–2.01)	1.21 (0.86–1.72)	1.56 (1.10–2.23)	1.30 (0.90–1.88)
Sex, man	0.88 (0.74–1.04)	0.85 (0.71–1.01)	0.95 (0.79–1.13)	0.93 (0.78–1.12)	1.02 (0.84–1.23)	0.99 (0.82–1.20)
Performance status
1	1.66 (1.37–2.01)	1.57 (1.29–1.92)	1.96 (1.60–2.40)	1.80 (1.47–2.21)	1.90 (1.53–2.36)	1.81 (1.45–2.26)
2+	2.61 (1.93–3.51)	2.42 (1.78–3.29)	3.13 (2.31–4.22)	2.78 (2.03–3.80)	3.10 (2 23–4.30)	2.90 (2.06–4.09)
Comorbidity CCI >3	1.75 (1.24–2.47)	1.33 (0.90–1.96)	2.12 (1.49–3.01)	1.38 (0.92–2.05)	1.85 (1.26–2.74)	1.22 (0.79–1.90)
Medication >5 drugs/d	1.39 (1.03–1.88)	1.02 (0.74–1.42)	1.61 (1.18-2.19)	1.02 (0.75-1.40)	1.60 (1.15–2.24)	1.13 (0.78–1.62)
Civil status, living alone	1.05 (0.87–1.26)	0.95 (0.79–1.15)	1.31 (1.08–1.60)	1.19 (0.98–1.45)	1.32 (1.07–1.62)	1.20 (0.97–1.48)
Right-sided colon cancer	1.21 (0.99–1.48)	1.18 (0.96–1.45)	1.60 (1.30–2.00)	1.54 (1.24-1.91)	1.69 (1.34–2.13)	1.64 (1.30–2.08)
Synchronous metastatic cancer	1.00 (0.83–1.20)	1.01 (0.84–1.21)	1.05 (0.87–1.27)	1.10 (0.91–1.34)	1.01 (0.83–1.24)	1.07 (0.87–1.32)
Previous adjuvant therapy	0.95 (0.78–1.16)	0.98 (0.80–1.20)	0.79 (0.64–0.97)	0.81 (0.65–1.00)	0.84 (0.68–1.05)	0.84 (0.68–1.06)
Leucocytes >7.3 10^9/L	1.59 (1.24–2.04)	1.56 (1.21–2.00)	1.76 (1.36–2.27)	1.76 (1.35–2.28)	1.66 (1.26–2.18)	1.66 (1.25–2.19)
Hemoglobin <7.3 (♀) / < 8.3(♂) mmol/L	0.61 (0.44–0.85)	0.70 (0.50–1.00)	0.47 (0.33–0.66)	0.57 (0.40–0.81)	0.51 (0.35–0.74)	0.59 (0.41–0.87)
LDH >255 μg/L	2.00 (1.56–2.57)	2.03 (1.56–2.65)	1.81 (1.40–2.35)	1.83 (1.40–2.40)	1.97 (1.51–2.58)	1.96 (1.48–2.59)
CEA <5 U/L	1.69 (1.35–2.12)	1.66 (1.32–2.09)	1.79 (1.40–2.29)	1.71 (1.33–2.19)	1.82 (1.41–2.36)	1.76 (1.35–2.29)
Treatment-related factors associated with outcomes
Reduced start dose	1.38 (1.16–1.65)	1.13 (0.93–1.38)	1.65 (1.37–1.97)	1.23 (1.00–1.50)	1.57 (1.29–1.92)	1.23 (0.99–1.54)
Monotherapy	2.01 (1.57–2.57)	1.52 (1.16–2.00)	1.93 (1.51–2.48)	1.21 (0.92–1.60)	1.75 (1.32–2.31)	1.15 (0.84–1.57)
Dose intensity cap./5-FU^b
75–90%	0.78 (0.61–1.00)	0.87 (0.67–1.13)	0.66 (0.53–0.84)	0.79 (0.61–1.00)	0.70 (0.54–0.89)	0.79 (0.61–1.03)
>90%	0.75 (0.59–0.95)	0.84 (0.65–1.09)	0.57 (0.45–0.71)	0.73 (0.57–0.93)	0.60 (0.47–0.76)	0.73 (0.56–0.96)
Dose intensity oxaliplatin^b
75–90%	0.89 (0.65–1.22)	0.99 (0.71–1.38)	0.72 (0.54–0.97)	0.89 (0.66–1.21)	0.76 (0.56–1.05)	0.92 (0.66–1.28)
>90%	0.70 (0.52–0.95)	0.76 (0.55–1.05)	0.68 (0.51–0.89)	0.87 (0.65–1.18)	0.69 (0.51–0.93)	0.84 (0.61–1.16)
Dose intensity cetuximab^b
75–90%	0.56 (0.19–1.64)	0.41 (0.13–1.30)	0.51 (0.17–1.56)	0.39 (0.12–1.31)	0.59 (0.19–1.86)	0.36 (0.10–1.27)
>90%	0.33 (0.13–0.82)	0.32 (0.12–0.89)	0.54 (0.22–1.31)	0.67 (0.22–2.04)	0.53 (0.20–1.38)	0.44 (0.14–1.39)
Dose intensity irinotecan^b
75–90%	1.32 (0.80–2.19)	1.47 (0.85–2.54)	1.00 (0.61–1.63)	1.09 (0.64–1.83)	0.95 (0.56–1.60)	1.04 (0.60–1.83)
>90%	1.18 (0.78–1.78)	1.34 (0.84–2.13)	0.68 (0.45–1.03)	0.85 (0.55–1.32)	0.68 (0.44–1.05)	0.82 (0.52–1.31)
Hospitalization	1.36 (1.13–1.65)	1.32 (1.08–1.60)	1.76 (1.47–2.11)	1.72 (1.43–2.06)	1.59 (1.31–1.93)	1.59 (1.30–1.93)

^aAdjusted for age, PS, and comorbidity.

^b<75% as reference.

^cCRC: CRC-related mortality CI confidence interval; CCI: Charlson Comorbidity Index.

Figure 2. Treatment outcomes comparing treated and non-treated patients stratified by age. (A) PFS; higher risk of progression for older compared with younger treated patients (p < .01), but after adjustments for PS and comorbidity there was no significant difference (ap = .11). (B) OS; higher risk of all-cause mortality for older compared with younger treated patients (ap < .01). No difference in non-treated patients (p = .40). (C) CRC-mortality; no age-dependent difference was found in risk of CRC-related death for treated (p = .16) or non-treated patients (p = .07). (D) Other causes of death; higher risk of non-CRC-related death in older compared with younger treated patients (ap < .01) No difference in non-treated patients (p = 0.17).

Figure 3. Kaplan–Meier curves showing PFS for patients with PS 0 and 1 given different dose intensities of chemotherapy as a monotherapy or as part of combination chemotherapy. (A) Patients given 5-FU/ capecitabine. (B) Patients given irinotecan.

Figure 4. Kaplan–Meier curves showing OS for patients with PS 0 and 1 given different dose intensities of chemotherapy as a monotherapy or as part of combination chemotherapy. Non-treated patients (dose = 0) are included. (A) Patients given 5-FU/ capecitabine. (B) Patients given irinotecan.