CAIRO 3: Maintenance Chemo Effective in Metastatic CRC

Maintenance treatment with capecitabine and bevacizumab after 6 cycles of CAPOX B is an effective treatment in patients with metastatic colorectal cancer, according to the final results of the CAIRO3 study.

CHICAGO-Maintenance treatment with capecitabine and bevacizumab after 6 cycles of capecitabine/oxaliplatin/bevacizumab (CAPOX B) is an effective treatment in patients with metastatic colorectal cancer, according to the final results of the CAIRO3 study presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting

“There is significant benefit in median PFS2, PFS1, and time to second progression,” said study presenter Miriam Koopman, MD, PhD, of the University Medical Center Utrecht in the Netherlands.

Patients enrolled in the study had to have stable disease or better after first-line treatment with 6 cycles of CAPOX-B, and be eligible for further treatment. Those 558 patients were then randomly assigned to observation (n = 279) or capecitabine plus bevacizumab (n = 279) until the first progression (PFS1) and then CAPOX-B was reintroduced until the second progression (PFS2).

The primary endpoint was PFS2. According to Dr. Koopman, PFS2 was considered to be equal to PFS1 for patients in whom CAPOX-B was not reintroduced after PFS1 for any reason. Sixty percent of patients assigned to observation and 47% of patients assigned to capecitabine/bevacizumab had reintroduction of CAPOX-B. There was a median follow-up of 48 months.

The median PFS1 was 4.1 months for the observation arm compared with 8.5 months for the maintenance arm (P < .0001; adjusted HR = 0.39; 95% CI, 0.33-0.48). The median PFS2 was 8.5 months for patients assigned to observation compared with 11.7 months for patients assigned to maintenance therapy (P < .0001; adjusted HR = 0.64; 95% CI, 0.53-0.76).

Patients assigned to maintenance therapy also had a significantly improved time to second progression compared with patients assigned to observation (13.9 vs 11.1 months; P < .0001; adjusted HR = 0.64; 95% CI, 0.53-0.77).

However, there was no significant difference between the two groups in overall survival. The median overall survival was 18.1 months for the observation arm compared with 21.6 months for the maintenance arm.

According to the results, these improvements in progression-free survival seen with maintenance therapy did not come at a cost of quality of life.

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

Preplanned subgroup analysis found that all subgroups had a benefit when assigned to maintenance therapy for PFS1 and PFS2 as compared to observation treatment.

“We found that there were no significant interactions for subgroups for PFS1, PFS2, and time to second progression, irrespective of treatment,” Koopman said. “However, we did find a significant interaction with overall survival for patients with metachronous disease, synchronous disease with or without resection of the primary tumor, WHO performance status, and the site of the primary tumor.”

“Patients with synchronous disease with resected primary tumor and patients with a complete/partial response as best response to induction treatment appear to benefit most from maintenance treatment in terms of overall survival,” she added.

In patients with complete or partial response, the median overall survival on the observation arm was 18.8 months compared with 24.1 months in the maintenance arm. Patients with stable disease in the observation arm had a median overall survival of 15.2 months compared with 16.9 months for patients in the maintenance arm.

In a podcast interview with Cancer Network, Leonard Saltz, MD, chief of the gastrointestinal oncology service at Memorial Sloan-Kettering Cancer Center, said that the results of the CAIRO 3 study show that there appears to be a benefit in terms of continuing maintenance chemotherapy in this patient population.

“To some degree, I find this a confirmation of some earlier studies that have been presented including the OPTIMOX 2 study,” Saltz said. “For anyone who was considering stopping therapy cold turkey this will provide some data justifying that continuation of fluoropyrimidines plus bevacizumab has some advantages over observation.”