Real-world evidence on adjuvant chemotherapy in older adults with stage II/III colon cancer

Table 1 Landmark trials for the combination of adjuvant chemotherapy with oxaliplatin and fluoropyrimidines in resected colorectal cancer

Clinical Trial	Regimen	Patients (n/age)	Stage	DFS	OS
				5-yr	6-yr
MOSAIC, 2004	FOLFOX4 vs LV5FU2	2246	II/III	73.3% vs 67.4%	72.9% vs 68.7%
		Age 18-75	40% Stage II		For stage III
		778, > 65 yr (34.6%)			No benefit for stage II at 6-yr and 10-yr
				4-yr	5-yr
NSABP-C-07, 2007	Weekly bolus 5-FU/LV ± Oxaliplatin (FLOX)	2407	II/III	73.2% vs 67.0%	N/A
		396, > 70 yr (16.4%)	695 Stage II (28.8%)		Unplanned subset analyses suggested no benefit for patients > 70 yr (71.6% vs 76.3%)
				7-yr	7-yr
NO16968, 2015	CAPOX (XELOX) vs 5-FU/Leucovorin (C. Mayo/R. Park)	1886	III	63% vs 56%	73% vs 67%
		409, > 70 yr (21.6%)		HR = 0.86 (95%CI: 0.64-1.16)	HR = 0.91 (95%CI: 0.66 TO 1.26)

DFS: Disease free survival; HR: Hazard ratio; OS: Overall survival.

Table 2 Real word data of older adults with stage II and III colon cancer

Ref.	Study design	n/stage	Age selection	Treatment arms/parameters	Conclusion
Sargent et al[103], 2001	Pooled analysis 7 trials	3351, stage II/III	≤ 50, 51- 60, 61-70, and > 70 yr	Fluorouracil plus leucovorin or levamisole vs surgery alone	Same benefit from fluorouracil-based adjuvant therapy as their younger counterparts
Sundararajan et al[17], 2002	Retrospective cohort	4768, node-positive	65 years of age or older	Association of 5-FU adjuvant therapy with survival	5-FU therapy is significantly associated with reduced mortality in older patients
Zuckerman et al[106], 2009	Observational, retrospective cohort	3016, stage III	aged 66 and older	5-FU or leucovorin within 6 mo after surgery	Elderly patients had a significant survival benefit associated with adjuvant chemotherapy
Jessup et al[107], 2005	Prospective data	85934, stage III	< 60, 60-69. 70-79, > 80 yr	Adjuvant chemotherapy usage and 5-yr survival	Elderly patients have the same benefit as younger patients but are less frequently treated
Neugut et al[108], 2006	Retrospective database	1722, stage III	≥ 65 years of age	Early discontinuation of FU-based chemotherapy	High percentage of early treatment discontinuation in the elderly population
Dobie et al[109], 2006	Retrospective SEER analysis	3193, stage III	65 years and older	Adjuvant chemotherapy completion and its relation to 3-year cancer mortality	Incomplete adjuvant chemotherapy associated to physical frailty and treatment complications
McCleary et al[12], 2013	Pooled analysis, ACCENT group	14528, stage II/III	age < 70 and age ≥ 70 years	Impact of age on colon cancer recurrence and mortality after adjuvant therapy	Reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting for patients > 70 years
Meyers et al[114], 2017	Systematic review	Stage II and III	age < 70 and age ≥ 70 years	Benefit from adjuvant chemotherapy (5-fluorouracil /leucovorin/ oxaliplatin or capecitabine/ oxaliplatin)	Patients with high-risk stage II disease may benefit from adjuvant chemotherapy
Green et al[117], 2019	Retrospective SEER-Medicare database analysis	31990, stage II/III	Aged 66-69, 70-74, 75-79, 80-84, 85-89 and 90+	Use and outcomes of adjuvant chemotherapy	Administration of adjuvant chemotherapy for colon cancer decreases with advancing age, but improved outcomes are seen in stage III patients under 90 years of age
Sanoff et al[121], 2012	Retrospective data source analysis	4060, stage III	< 50, 50-64, 65-69, 70-74 yr	Oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy	The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community

5-FU: 5-fluorouracil; SEER: Surveillance, Epidemiology, and End Results; ACCENT: Adjuvant Colon Cancer End Points.