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.

3521 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. [Table: see text]

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Bevacizumab (bev) in combination with capecitabine (cape) for the first-line treatment of elderly patients with metastatic colorectal cancer (mCRC): Results of a randomized international phase III trial (AVEX).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.337 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 337-337 ◽

Cited By ~ 11

Author(s):

David Cunningham ◽

Istvan Lang ◽

Vito Lorusso ◽

Janja Ocvirk ◽

Dongbok Shin ◽

...

Keyword(s):

Elderly Patients ◽

Statistical Significance ◽

Performance Status ◽

Randomized Study ◽

Single Agent ◽

Phase Iii ◽

Efficacy And Safety ◽

First Line ◽

Open Label ◽

Phase Iii Trial

337 Background: Elderly patients (pts) comprise the majority of pts diagnosed with mCRC, although they are in general underrepresented in clinical trials. AVEX, an open-label phase III trial, evaluated the efficacy and safety of cape ± bev in elderly pts with previously untreated mCRC. Methods: Pts ≥70 years with mCRC, for whom single-agent chemotherapy was deemed appropriate, were randomized 1:1 to receive first-line cape (1000 mg/m2 bid days 1–14) as monotherapy or in combination with bev (7.5 mg/kg) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), and safety. The study was powered to show a difference in PFS, but not OS, between treatment arms. PFS and OS estimates were calculated using Kaplan-Meier methods. Results: 280 pts across 10 countries were randomized to cape + bev (n=140) and cape alone (n=140). Median age at enrollment was 76 years (range, 70–87), and 91.1% of pts had an ECOG performance status of 0–1. Baseline pt and disease characteristics were well balanced between arms. Bev + cape was associated with significantly prolonged PFS compared with cape alone (median of 9.1 vs 5.1 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41–0.69; p<0.001). The ORR was also significantly improved in the bev + cape arm (19.3% vs 10.0%; p=0.042). OS was longer in pts treated with bev + cape vs cape alone, although this difference did not reach statistical significance (median of 20.7 vs 16.8 months; HR, 0.79; 95% CI, 0.57–1.09; p=0.182). Grade ≥3 adverse events occurred in 59.0% vs 44.1% of pts in the bev + cape and cape arm, respectively. Treatment was in general well tolerated and the safety profile consistent with previously reported data for bev + cape. Conclusions: This is the first randomized study prospectively evaluating bev specifically in elderly pts with mCRC. Based on the efficacy and safety results, bev plus cape might be an optimal treatment approach to improve outcomes in elderly pts. Clinical trial information: NCT00484939.

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Sequential first-line treatment for metastatic colorectal cancer with capecitabine, irinotecan, and bevacizumab: Capecitabine plus bevacizumab (Cape-Bev) versus capecitabine, irinotecan plus bevacizumab (CAPIRI-Bev): The AIO KRK 0110/ML22011 randomized, phase III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.tps3639 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. TPS3639-TPS3639

Author(s):

Clemens Albrecht Giessen ◽

Dominik Paul Modest ◽

Sebastian Stintzing ◽

Ludwig Fischer von Weikersthal ◽

Ursula Vehling-Kaiser ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Single Agent ◽

Cytotoxic Agents ◽

Phase Iii ◽

Time To Failure ◽

Line Treatment ◽

First Line ◽

Phase Iii Trial ◽

First Line Treatment

TPS3639 Background: Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question in bevacizumab-based first-line treatment including escalation- and de-escalation strategies. Methods: The AIO KRK 0110/ML22011 trial (ClinicalTrials.gov NCT01249638) is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of Cape-Bev versus CAPIRI-Bev in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, ECOG PS 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m2 bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m2 BID for 14d (d1-14), irinotecan 200 mg/m2 (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumor tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are ORR, OS, PFS, safety and quality of life. Conclusion: The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with CAPIRI-Bev and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary. By January 2012, 79 of planned 516 patients have been enrolled.

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