Maintenance Therapy in Metastatic Colorectal Cancer

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Moderator, John L. Marshall, MD, presents a case based discussion focused on the treatment of a 60 year-old man with metastatic colorectal cancer (mCRC). In the case study, the patient presented with 3 liver and 5 lung metastases and retroperitoneal adenopathy. After 6 months of frontline chemotherapy, the patient now has asymptomatic disease with a decreasing CEA level.

A series of clinical trials have indicated the dangers of continuing treatment with cytotoxics, specifically oxaliplatin, for extended period of time, notes Fadi Braiteh, MD, CPI. As a result, maintenance therapies are an attractive treatment option for patients with stable disease.

In the phase III DREAM study, maintenance bevacizumab with or without erlotinib, based on KRAS status, was administered following induction chemotherapy with bevacizumab. This trial is unique, since erlotinib is not a standard treatment for CRC, notes Braiteh.

Interestingly, the trial showed an improvement in response and progression-free survival in favor of bevacizumab plus erlotinib compared to bevacizumab alone. However, an improvement in overall survival was not noted. Also of interest, the KRAS status was not predictive of response to erlotinib, emphasizing that not all EGFR inhibitors are the same, notes Braiteh.

However, a more promising approach to maintenance therapy was explored in the phase III CAIRO3 trial, which compared maintenance treatment with bevacizumab and capecitabine to observation following an induction treatment of 6 cycles (18 weeks) of oxaliplatin, capecitabine, and bevacizumab. In the trial, maintenance therapy was given until progression, which occurred after a median of 15.4 months compared with 11.5 months for patients treated with bevacizumab plus capecitabine and observation, respectively, notes Axel Grothey, MD.

This approach is particularly useful if you want to stop treatment with oxaliplatin, which can often lead to undesirable toxicity, notes Grothey. In general, this maintenance strategy is well tolerated and effective. In general, this approach has become the standard of care, for most patients, agrees the panel. In most situations, the panelists continue maintenance treatment with bevacizumab and capecitabine for an extended period of time, if toxicity does not prevent it.

In clinical trials, some groups are administering an induction regimen followed by maintenance therapy, while mutational analyses are completed. Once these tests are returned, a targeted treatment can be examined, Grothey notes.