. 2023 Jul 27;26(1):69–84. doi: 10.1007/s12094-023-03243-0

Table 2.

Evaluation of first-line treatments in the elderly patient with metastatic CRC

Study	N Age	Treatment scheme	GA	Efficacy
Phase III AVEX [50]	N = 280 ≥ 70	A: Capecitabine B: Capecitabine + bevacizumab	No	PFS: 5.2 vs. 9.1 m; p < 0.0001 OS: 20.7 vs. 16.8 m; p = 0.18 RR: 19% vs. 10%; p = 0.04
Phase III SOLSTICE [51, 52]	N = 856 435 ≥ 75 (Fragile)	A: TAS-102 + bevacizumab B: Capecitabine + bevacizumab	Yes	PFS: 9.4 vs. 9.3 m; p = 0.0464 (superiority p < 0.021) OS: Pending RR: 36% vs. 42%; p = 0.0942
Phase III [53] JCOG1018	N = 251 ≥ 70	A: FP + bevacizumab B: FP + oxaliplatin + bevacizumab	Yes	PFS: 9.4 vs. 10 m; p = 0.086 OS: 21.3 vs. 19.7 m RR: 30% vs. 48%
Phase II-III AGITG MAX [54]	N = 99 Subgroup ≥ 75	C: Capecitabine CB: Capecitabine + bevacizumab CBM: Capecitabine + bevacizumab + Mitomycin C	No	PFS CB vs. C: 0.52 (0.32–0.86); p = 0.01 PFS CBM vs. C: 0.38 (0.23–0.64); p = 0.001 OS CB vs. C: 0.80 (0.47–1.36); p = 0.41 OS CBM vs. C: 0.78 (0.46–1.34); p = 0.36 RR C vs. CB vs. CBM: 28% vs. 23% vs. 57%; p = 0.08
Phase II [55] PRODIGE 20	N = 102 ≥ 75	A: FOLFOX/FOLFIRI/ 5FU-LV B: FOLFOX/FOLFIRI/5FU-LV + bevacizumab	No	PFS: 7.8 vs. 9.7 m; HR 0.79 [95% Cl 0.53–1.17] OS: 19.8 vs. 21.7 m; HR = 0.73 [95% Cl 0.48–1.11] RR: 33% vs. 37%
Phase III-II AVF2107-AVF2192 pooled [56]	N = 439 ≥ 65	A: 5FU-LV bolus B: 5FU-LV bolus + bevacizumab	No	PFS: 6.2 vs. 9.2 m; p < 0.001 OS: 14.3 vs. 19.3 m; p = 0.006 RR: 29% vs. 34%; p = ns
Phase II Sastre et al. [57]	N = 66 ≥ 70	Capecitabine + cetuximab	No	PFS: 8.4 RAS WT vs. 6 RAS mut; p = 0.024 OS: 8.4 RAS WT vs. 6 RAS mut; p = 0.024 RR: 48% RAS WT vs. 21% RAS mut; p = 0.027
Phase II PANDA [58]	N = 185 ≥ 70	A: FOLFOX + panitumumab B: 5FU/LV + panitumumab	Yes	PFS: 9.6 vs. 9.1 m OS: Pending RR: 65% vs. 57%; p = ns

Study

N Age

Treatment scheme

Efficacy

Phase III

AVEX [50]

N = 280

≥ 70

A: Capecitabine

B: Capecitabine + bevacizumab

PFS: 5.2 vs. 9.1 m; p < 0.0001

OS: 20.7 vs. 16.8 m; p = 0.18

RR: 19% vs. 10%; p = 0.04

Phase III

SOLSTICE [51, 52]

N = 856

435 ≥ 75 (Fragile)

A: TAS-102 + bevacizumab

B: Capecitabine + bevacizumab

Yes

PFS: 9.4 vs. 9.3 m; p = 0.0464 (superiority p < 0.021)

OS: Pending

RR: 36% vs. 42%; p = 0.0942

Phase III [53]

JCOG1018

N = 251

≥ 70

A: FP + bevacizumab

B: FP + oxaliplatin + bevacizumab

Yes

PFS: 9.4 vs. 10 m; p = 0.086

OS: 21.3 vs. 19.7 m

RR: 30% vs. 48%

Phase II-III

AGITG MAX [54]

N = 99

Subgroup ≥ 75

C: Capecitabine

CB: Capecitabine + bevacizumab

CBM: Capecitabine + bevacizumab + Mitomycin C

PFS CB vs. C: 0.52 (0.32–0.86); p = 0.01

PFS CBM vs. C: 0.38 (0.23–0.64); p = 0.001

OS CB vs. C: 0.80 (0.47–1.36); p = 0.41

OS CBM vs. C: 0.78 (0.46–1.34); p = 0.36

RR C vs. CB vs. CBM: 28% vs. 23% vs. 57%; p = 0.08

Phase II [55]

PRODIGE 20

N = 102

≥ 75

A: FOLFOX/FOLFIRI/ 5FU-LV

B: FOLFOX/FOLFIRI/5FU-LV + bevacizumab

PFS: 7.8 vs. 9.7 m; HR 0.79 [95% Cl 0.53–1.17]

OS: 19.8 vs. 21.7 m; HR = 0.73 [95% Cl 0.48–1.11]

RR: 33% vs. 37%

Phase III-II

AVF2107-AVF2192 pooled [56]

N = 439

≥ 65

A: 5FU-LV bolus

B: 5FU-LV bolus + bevacizumab

PFS: 6.2 vs. 9.2 m; p < 0.001

OS: 14.3 vs. 19.3 m; p = 0.006

RR: 29% vs. 34%; p = ns

Phase II

Sastre et al. [57]

N = 66

≥ 70

Capecitabine + cetuximab

PFS: 8.4 RAS WT vs. 6 RAS mut; p = 0.024

OS: 8.4 RAS WT vs. 6 RAS mut; p = 0.024

RR: 48% RAS WT vs. 21% RAS mut; p = 0.027

Phase II

PANDA [58]

N = 185

≥ 70

A: FOLFOX + panitumumab

B: 5FU/LV + panitumumab

Yes

PFS: 9.6 vs. 9.1 m

OS: Pending

RR: 65% vs. 57%; p = ns

5FU 5-fluorouracil, CRC colorectal cancer, FOLFIRI 5FU and folinic acid with irinotecan, FOLFOX 5FU and folinic acid with oxaliplatin, FP fluoropirimidina (5FU/capecitabina, GA geriatric assessment, LV leucovorin, m month, mut mutant, OS overall survival, PFS progression-free survival, RAS rat sarcoma virus, TAS-102 trifluridine/tipiracil, WT wild-type, RR response rate