A Post Hoc Analysis of Older Patients with Metastatic Colorectal Cancer Receiving Oxaliplatin-Based Chemotherapy Plus Bevacizumab: The Randomized Obelics Study.

BACKGROUND

Phase II trials and subgroup analyses of clinical studies suggest that bevacizumab plus an oxaliplatin-based chemotherapy doublet is effective and tolerable in fit older patients with metastatic colorectal cancer (mCRC).

OBJECTIVE

To evaluate the influence of age on the incidence of side effects and efficacy of this combination in patients with mCRC randomized in the prospective phase III OBELICS study.

METHODS

In total, 230 patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 out of 1 were retrieved on the basis of age (190 < 70 years and 40 ≥ 70 years). They received bevacizumab 5 mg/kg administered either on the same day as chemotherapy (standard arm) or 4 days before chemotherapy (experimental arm) and oxaliplatin 85 mg/m on day 1, plus capecitabine 1000 mg/m twice a day (bid) orally on days 1-10 or levofolinic acid, 200 mg/m, bolus 5-fluorouracil (5-FU) 400 mg/m, and a 46-h intravenous infusion of 5-FU 2400 mg/m, every 14 days; oxaliplatin was discontinued after 12 cycles. The primary end point was the overall response rate (ORR).

RESULTS

Efficacy and toxicity analyses are reported in aggregate form because there were no statistically significant differences between the two arms. Patient characteristics are well balanced between older and younger patients. No difference in ORR was observed between the two groups (50% for the older patients versus 57.9% for the younger ones; p = 0.36). The median PFS was 10.8 (95% confidence interval [CI], 9.9-12.2) and 11.3 (95% CI 8.3-13.0) months, respectively, for subjects younger than 70 years and those aged ≥ 70 years, with an adjusted hazard ratio (HR) of 1.16 (95% CI 0.80-1.68; p = 0.43). The median OS was 26.2 (95% CI 23.3-32.7) for the former and 23.2 (95% CI 17.3-35.3) months for the latter, respectively, with an adjusted HR of 1.60 (95% CI 1.08-2.37; p = 0.027). Considering all forms of toxicity, the most severe ones were not statistically different between the two groups (65% for the older patients and 60.6% for the younger ones, p = 0.61).

CONCLUSIONS

Bevacizumab plus an oxaliplatin-based chemotherapy doublet were effective in older patients randomized in the OBELICS trial, and the adverse event profile was not dissimilar from that of younger patients; no new safety concerns were identified. This post hoc analysis confirms that fit older patients with mCRC should be considered for treatment with this regimen.