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
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 |
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---|---|---|---|---|---|---|---|---|---|
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 |
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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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