Bevacizumab continued beyond first progression beneficial in patients with metastatic colorectal cancer previously treated with bevacizumab and chemotherapy
Results of the first randomized study to prospectively investigate the impact of bevacizumab continuation beyond first progression
- Date : 11 Jun 2012
- Topic : Gastrointestinal cancers
A new study has confirmed that continuing bevacizumab treatment beyond first progression, while modifying chemotherapy, can be beneficial for patients with metastatic colorectal cancer. In the first randomized study to prospectively investigate the impact of bevacizumab continuation in this setting, the study researchers noted a significant improvement in both overall and progression-free survival.
Bevacizumab administered in combination with fluoropyrimidine-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer and second-line treatment in bevacizumab-naive patients. Preclinical observational studies have shown a rationale to continue bevacizumab from one treatment line to another treatment line.
In this international study, Dr Dirk Arnold, director of the Hubertus Wald Tumor Center, University Cancer Center of University Clinic Eppendorf, in Hamburg, Germany, and colleagues randomized 820 patients with unresectable, histologically confirmed metastatic colorectal cancer who had progressed within 3 months of discontinuing first-line bevacizumab plus chemotherapy to either second-line fluoropyrimidine-based therapy plus bevacizumab or placebo.
The choice of oxaliplatin- or irinotecan-based chemotherapy as second-line therapy depended on the regimen used in the first-line setting. The primary end point was overall survival; secondary end points included progression-free survival, response rate, and safety.
According to the study researchers the trial clearly met its end point of overall survival, with a statistically significant improvement in overall survival. Median survival was longer with chemotherapy plus bevacizumab than with chemotherapy alone (11.2 vs 9.8 months).
Median progression-free survival was also improved in this setting (5.7 vs 4.1 months, p<0.0001). The response rate was 5.4% with chemotherapy plus bevacizumab and 3.9% with chemotherapy alone.
Treatment was well tolerated in both study groups, and adverse events associated with bevacizumab were comparable with those observed in previous studies. Bevacizumab-related adverse events were no worse when the agent was continued after progression.
The results of the trial were presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (Chicago, 1-5 June).
Clinical evidenceneeded to justify preclinical observations
Many oncologists are already extending bevacizumab beyond first progression, and results from this study are the proof of concept in the clinical setting. The study results raise also the question on the financial impact of therapy continuation. Although it was well designed and demonstrates the benefit of bevacizumab continuation, the study doesn't address the magnitude of that benefit.
Previous studies have hinted at the benefit of continuing bevacizumab in patients with advanced colorectal cancer. One large observational study reviewed 1445 metastatic colorectal cancer patients after they progressed on various chemotherapy regimens and bevacizumab. Patients who changed chemotherapy after progression but continued on bevacizumab had an overall survival of 31.8 months, compared with 19.9 months for those who changed chemotherapy regimens but discontinued bevacizumab. Multivariate analysis showed that bevacizumab was strongly associated with improved survival.
The results of this study clearly provide a new second-line treatment option for patients who have already been treated with a combination bevacizumab regimen. Furthermore, these findings might serve as a potential new model for treatment approaches across multiple lines in metastatic colorectal cancer and across other tumor types, which is being investigated. Additional analysis of this study, including biomarker evaluation, is ongoing.
The study was funded by Genentech.
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