Maintenance treatment prolongs progression-free survival in metastatic colorectal cancer

Last Updated: 2015-04-22

By Will Boggs MD

NEW YORK (Reuters Health) - Maintenance treatment with capecitabine and bevacizumab prolongs progression-free survival in patients with metastatic colorectal cancer, according to the CAIRO3 trial.

"We finally have an answer" on whether to continue or stop chemotherapy plus bevacizumab, and "maintenance treatment leads to a better survival without compromising quality of life," Dr. Miriam Koopman from University Medical Center Utrecht in the Netherlands, who worked on the study, told Reuters Health by email.

Although the availability of new drugs has improved the prognosis of patients with metastatic colorectal cancer, the optimal use of drugs and duration of treatment remain uncertain.

Dr. Koopman and colleagues in the Dutch Colorectal Cancer Group compared maintenance treatment with capecitabine and bevacizumab versus observation until disease progression in an open-label, randomized trial of 588 patients with metastatic colorectal cancer who were without disease progression after six cycles of capecitabine, oxaliplatin and bevacizumab (CAPOX-B).

After their first progression (PFS1), all patients were to receive the same induction regimen (CAPOX-B) until second progression (PFS2), which was the study's primary endpoint.

Median PFS1 was significantly longer in the maintenance treatment group (8.5 months) than in the observation group (4.1 months). Median PFS2 was also significantly longer with maintenance treatment (11.7 months versus 8.5 months for observation).

Overall survival was longer with maintenance treatment (median, 21.6 months) than with observation (median, 18.1 months), but the difference fell short of statistical significance, the researchers report in the The Lancet, online April 8.

Patients experienced significantly more adverse events, including hand-foot syndrome, with maintenance treatment than with observation, but this did not translate into clinically relevant differences in global quality of life between the groups.

"Maintenance treatment with capecitabine and bevacizumab should be deemed the preferred strategy in patients with metastatic colorectal cancer with stable disease or better after initial treatment with combination chemotherapy and bevacizumab," the researchers conclude.

Dr. Koopman said maintenance therapy should be continued indefinitely. "However, if there is unacceptable toxicity, of course this treatment should not be continued," she added. "Since treatment is palliative, eventually all patients will relapse. Future research should define whether there are subgroups for whom observation may be appropriate."

Dr. Axel Grothey from Mayo Clinic Rochester, Minnesota, told Reuters Health by email, "I do recommend maintenance therapy for most of my patients with colorectal cancer (CRC) when I started with a bevacizumab-containing regimen as first-line."

"The future lies in better profiling patients' tumors and developing specifically targeted agents," said Dr. Grothey, who co-wrote an editorial on the findings. "At this point in time, though, non-specific drugs like TAS-102 will next be integrated in treatment algorithms. TAS-102 has shown to improve overall survival in patients with CRC. A subset of patients, likely the ones with so-called hypermutated CRC, could also benefit from immunotherapy."

"Strategic planning of treatment algorithms and proactive management of toxicities are critical to maximize outcome for patients with CRC," Dr. Grothey said.

Roche and Sanofi provided financial support for the study, and Roche had various relationships with three of the 23 authors, including Dr. Koopman.

SOURCE: http://bit.ly/1IHq2N7 and http://bit.ly/1Phvom9

Lancet 2015.