Maintenance Capecitabine/Bevacizumab Delays Disease Progression in Metastatic Colorectal Cancer and Extends Survival in Subgroups


Key Points

  • The final results of CAIRO3 validated the benefit of maintenance capecitabine plus bevacizumab after first-line induction chemotherapy in patients with metastatic colorectal cancer.
  • Time to first and to second disease progression were both significantly prolonged in the maintenance arm.
  • Two subsets of patients also experienced an overall survival benefit: those with synchronous metastases whose primary tumor was resected, and patients who achieved a complete or partial response to induction therapy.

According to the final results of the phase III CAIRO3 trial by the Dutch Colorectal Cancer Group, maintenance treatment with capecitabine plus bevacizumab (Avastin) significantly delayed progression compared to observation in patients with metastatic colorectal cancer, and in a subset of patients, also conveyed an overall survival benefit. The findings were reported at the 2014 Gastrointestinal Cancers Symposium in San Francisco (Abstract LBA388).

Maintenance treatment with capecitabine plus bevacizumab after six cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) significantly prolonged the time to disease progression and the time from randomization to progression after reintroduction of CAPOX-B, which was the study’s primary endpoint, according to Miriam Koopman, MD, of University Medical Center Utrecht in the Netherlands.

“Preplanned subgroup analyses showed the benefit of maintenance treatment in all subgroups for the primary endpoint, and an overall survival benefit for maintenance treatment in patients with synchronous disease with resection of the primary tumor, and in patients with a complete or partial response as best response on induction treatment,” she said.

Study Details

To help define the optimal duration of chemotherapy and bevacizumab in metastatic colorectal cancer, CAIRO3 evaluated the efficacy of maintenance with capecitabine plus bevacizumab vs observation in patients without disease progression during induction treatment with CAPOX-B.  

The 558 previously untreated metastatic patients enrolled in CAIRO3 achieved a response or stable disease after six cycles of CAPOX-B and were then randomly assigned to continue on maintenance capecitabine/bevacizumab or to undergo observation. The maintenance regimen was capecitabine at 625 mg/m2 twice daily, given continuously with bevacizumab at 7.5 mg/kg every 3 weeks. Upon first progression, patients in both arms received CAPOX-B until second progression, which was the primary endpoint. After a median follow-up of 48 months, CAPOX-B was reintroduced to 61% of the observation arm, compared to 47% of the maintenance arm.

Median first progression occurred at 4.1 months in the observation arm and 8.5 months in the maintenance arm, a 57% reduction in risk of progression (P < .0001). Median second progression, the primary endpoint, occurred at 8.5 months vs 11.7 months, respectively, a 33% reduction in risk (P < .0001), Dr. Koopman reported.

She emphasized that the time to first and second progression was assessed from randomization and did not include the 4 to 5 months of induction treatment. She also noted that second progression was considered equal to first progression for patients in whom CAPOX-B was not reintroduced after first progression for any reason.

The time to second progression of disease included patients who received any treatment after first progression, including CAPOX-B and other regimens or single agents. Median time to second progression of disease was 11.1 months with observation and 13.9 months with maintenance, a 32% reduction in risk with maintenance (P < .0001).

Median overall survival was 18.1 months with observation and 21.6 months with maintenance, which was not a significant difference (hazard ratio 0.89; P = .22).

The drugs administered during metastatic disease were not significantly different between the arms, with about half the patients in each arm receiving a total of four drugs and 12% receiving five.

“Quality of life was maintained during maintenance treatment, and was clinically not inferior compared to the quality of life in the observation arm,” Dr. Koopman noted.

Interesting Subgroup Differences

The benefit of maintenance was present in all subgroups for the primary endpoint, and for first progression and time to second progression of disease, but some interesting treatment interactions emerged upon deeper analysis.

Multivariable analysis for survival, with treatment adjusted for a series of potentially confounding factors at baseline, showed significant interactions for treatment (observation vs maintenance) with resection of the primary tumor (yes vs no) and synchronous vs metachronous metastases at baseline (P < .0001 for both interactions), Dr. Koopman reported.

The greatest benefit was observed for the 180 patients with synchronous metastases whose primary tumors were resected. With maintenance, these patients achieved a median overall survival of 25 months, vs 18 months with observation (P < .0001). For the 230 patients with synchronous metastases and no resection of the primary tumor, median overall survival was 16.3 months with observation and 14.9 months with maintenance, she reported.

Patients who achieved a complete or partial response on induction treatment before randomization also had very favorable median overall survival with maintenance, 24.1 months vs 18.8 months with observation (P < .0001).

Study author Cornelis J.A. Punt, MD, PhD, reported receiving honoraria from Roche and a consultant or advisory role with Roche.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.