Cancer Treatment Today

Some oncologists recommend continuing Avastin with a new regimen after progression. There is no published evidence that such a strategy is beneficial and Avastin does have potential side effects. A suggestion that Avastin may be modifying disease progression even after it failed to control recurrence comes from a retrospective review. BRiTE (Bevacizumab Regimens: Investigation of Treatment Effects and Safety) observed progress of three groups of patients when their cancer got worse after their first chemotherapy treatments. All patients had Avastin as part of the first chemo, some continued it beyond that first cancer progression. IN BRITE, it appeared that continuing Avastin past progression into second line was beneficial. Since this study,  The TML study showed that BEV + CT (crossed over from 1L regimen) continued beyond progression significantly prolongs OS and PFS in 2nd line  mCRC.

Overall survival after progression improved with bevacizumab to a median of 11.2 months compared with 9.8 on chemotherapy alone. While a small difference, the hazard ratio (HR) of 0.81 for death was statistically significant at P=0.0062. The same was true for PFS. The combination of bevacizumab and chemotherapy in second-line was associated with an HR of 0.68 for progression or death (P<0.0001). Median PFS was 5.7 and 4.1 months, respectively. Continuing bevacizumab after the first progression with metastatic cancer didn’t appear to add significantly to toxicity. The biggest difference in the rate of serious adverse events was in neutropenia, where the rate was 16% with the combination of treatments compared with 13% on chemotherapy alone.  Another study that supports the practice of continuing Avastin after failure of Avastin containing first line regimen is the ECOG study (Dirk et al). The indication for Avastin for colon cacner can be interpereted to support such use, although it predates the time when such use began to be seriousely proposed. It says: ” Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy.”

So, now the patient who progressed on Avastin has two options, switch the chemo drugs while continuing Avastin, or switch Avastin to Zaltrap. The best one strategy has not been defined and NCCN lists both as an appropriate option. There is no experimental evidence that supports using or continuing Avastin beyond second line.

Grothey, Axel, Sugrue, Mary M., Purdie, David M., Dong, Wei, Sargent, Daniel, Hedrick, Eric, Kozloff, Mark
Bevacizumab Beyond First Progression Is Associated With Prolonged Overall Survival in Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study (BRiTE)
J Clin Oncol 2008 26: 5326-5334

S. Kopetz and J. L. Abbruzzese
Hidden Biases in an Observational Study of Bevacizumab Beyond Progression
J. Clin. Oncol., April 1, 2009; 27(10): 1732 – 1733.

L. M. Ellis and D. G. Haller
Bevacizumab Beyond Progression: Does This Make Sense?
J. Clin. Oncol., November 20, 2008; 26(33): 5313 – 5315.

A. L. Cohn, T. Bekaii-Saab, J. C. Bendell, H. Hurwitz, M. Kozloff, N. Roach, H. Tezcan, S. Feng, A. Sing, A. Grothey, on behalf of the ARIES Study InvestigatorsClinical outcomes in bevacizumab (BV)-treated patients (pts) with metastatic colorectal cancer (mCRC): Results from ARIES observational cohort study (OCS) and confirmation of BRiTE data on BV beyond progression (BBP).
J Clin Oncol 28:15s, 2010 (suppl; abstr 3596)

Dirk Arnold et al, Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: Results of a randomized phase III intergroup study (TML study). J Clin Oncol 30, 2012 (suppl; abstr CRA3503)