Efficacy and safety according to age subgroups in AVEX, a randomized phase III trial of bevacizumab in combination with capecitabine for the first-line treatment of elderly patients with metastatic colorectal cancer.

Authors

null

Mark P. Saunders

Christie Hospital NHS Foundation Trust, Withington, United Kingdom

Mark P. Saunders , Istvan Lang , Eugenio Marcuello , Vito Lorusso , Janja Ocvirk , Dongbok Shin , Derek J. Jonker , Stuart Osborne , Markus Loeffler , Daniel Waterkamp , David Cunningham

Organizations

Christie Hospital NHS Foundation Trust, Withington, United Kingdom, National Institute of Oncology, Budapest, Hungary, Hospital de Sant Pau de Barcelona, Barcelona, Spain, Oncologic Institute, Vito Fazzi Hospital, Bari, Italy, Institute of Oncology Ljubljana, Ljubljana, Slovenia, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea, The Ottawa Hospital Cancer Center, Ottawa, ON, Canada, F. Hoffmann-La Roche Ltd, Basel, Switzerland, The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom

Research Funding

Pharmaceutical/Biotech Company

Background: Elderly patients (pts) are underrepresented in clinical trials. The open-label phase III trial AVEX evaluated the benefit of adding bevacizumab (BEV) to capecitabine (cape) in elderly pts with previously untreated metastatic colorectal cancer (mCRC). This analysis explores clinical outcomes by age subgroup. Methods: In AVEX, 280 pts ≥70 y with mCRC for whom single-agent chemotherapy was deemed appropriate, were randomized to first-line cape (1000 mg/m2bid days 1–14) alone (n=140) or with BEV (7.5 mg/kg) q3w (n=140). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), overall response rate, and safety. The study was powered to show a difference in PFS but not OS. A post hoc analysis was conducted to assess PFS, OS, and safety in pts 70–74 y, 75–79 y, and ≥80 y. Results: Median age was 76 y (range, 70–87). In the overall population, BEV + cape significantly prolonged PFS compared with cape (median 9.1 vs 5.1 mo; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41–0.69; p<.001). Differences in OS did not reach statistical significance in the overall population (HR, 0.79; 95% CI, 0.57–1.09; p=.182). Treatment was well tolerated. Results according to age are shown (Table). Conclusions: The addition of BEV to cape was associated with significant improvements in PFS in the overall elderly mCRC population and within age subgroups. The safety profile of BEV + cape was consistent across age groups. Clinical trial information: NCT00484939.

70–74 y
75–79 y
≥80 y
Cape + BEV
n=55
Cape n=46 Cape + BEV
n=57
Cape n=66 Cape + BEV
n=28
Cape n=28
Median PFS, mo (95% CI) 7.6
(6.0–11.8)
5.0
(4.0–6.5)
9.8
(7.1–11.4)
5.1
(4.1–7.4)
10.5
(5.0–14.5)
5.1
(2.2–7.1)
PFS HR (95% CI)
Log-rank p
0.52
(0.32–0.83) <.001
0.60
(0.40–0.89)
.016
0.36
(0.19–0.71)
.003
Median OS, mo (95% CI) 20.7
(13.7–26.1)
22.2
(9.7–42.7)
19.8
(13.8–27.3)
17.4
(11.9–23.0)
19.7
(7.5–26.9)
12.6
(6.6–17.0)
OS HR (95% CI)
Log-rank p
0.91
(0.50-1.66)
.55
0.79
(0.48-1.30)
.37
0.62
(0.31-1.24)
.24
Best ORR (%)
Fisher’s exact p
25.5 10.9 15.8 12.1 14.3 3.6
.076 .607 .352
Grade ≥3
adverse events, %
n=54
63.0
n=46
41.3
n=53
54.7
n=64
40.6
n=27
59.3
n=26
57.7

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Abstract Details

Meeting

2013 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer

Clinical Trial Registration Number

NCT00484939

Citation

J Clin Oncol 31, 2013 (suppl; abstr 3521)

DOI

10.1200/jco.2013.31.15_suppl.3521

Abstract #

3521

Poster Bd #

13

Abstract Disclosures