Maintenance treatment with bevacizumab in metastatic colorectal cancer: intermittent or continuous therapy? A monoinstitutional observational study

Background: The main objective of care in patients with mCRC is survival prolongation preserving the quality of life (QoL). Optimal duration of chemotherapy (CT) is still a matter of debate, such as the treatment strategies that could be adopted (maintenance CT vs observation). Intermittent CT resulted not inferior to continuous CT in GISCAD Study. We hypothesized that bevacizumab could be administered intermittently either. Methods: In this retrospective study we evaluated 73 patients (pts) with mCRC with stable or responsive disease after CT (FOLFIRI) and Bevacizumab as first or second-line treatment. We observed 3 groups: A (23 pts): maintenance therapy with de Gramont-Bevacizumab 2 months on/2 months off until progression (intermittent strategy); B (30 pts): no maintenance treatment; C (20 pts): induction treatment as first line followed by continuous maintenance with de Gramont-Bevacizumab. Results: The median number of CT courses was: A 34 (range 20-56), B 12, C 22 (range 16-25). Response rate was similar in groups A and C (A:13/23, C:12/20) and lower in Group B (13/30). In Group A increase of response was observed in 6 pts in post-induction time. No increase or additional response was observed in Group B and C. Median progression free survival (PFS), was 21.2 months (m) in Group A (19-26 m), 9 m in Group B (6.6-12.9 m), 12 m in Group C (10.4-13.3 m), with statistically significant difference in favor of intermittent stratedy (p = 0.0095). Median overall survival (OS) was: A 60.5 m (35.6-96.2 m), B 27.2 m (19.5-39.9 m), C 22.8 m (18.6-31 m); with a statistically significant survival advantage for intermittent strategy (p = 0.0006). The most frequent adverse events (AEs) of all grades were: hypertension, neutropenia, thrombocytopenia, diarrhea, asthenia. No toxic death was observed. AEs of all grades were more frequent in group C (15% Grade 3-4), vs Group A and B (10% Grade 3-4). Conclusions: According to our retrospective analysis, intermittent maintenance treatment with CT and Bevacizumab appears to be a feasible strategy in pts with stable or responsive disease. PFS and OS resulted longer in pts treated with intermittent strategy. The study has many biases: pts heterogeneity, small sample size, retrospective nature, lack of biologic and pharmacokinetic data. However we can conclude that intermittent strategy could improve pts outcome with acceptable toxicity profile and should be considered in a prospective study.