One of the most common side effects of many different anti-angiogenic agents, which are felt to decrease the tumor’s blood supply, is high blood pressure, also known as hypertension. The cause of this isn’t really known, but most patients develop some degree of high blood pressure. What is interesting is that there is growing evidence that this may not just be an unwanted side effect, but rather a marker of a probability of doing better, similar to the correlation of rash with longer survival in patients receiving EGFR inhibitors.
For this, we can start by looking at results from a recent study of the anti-angiogenic agent sorafenib (nexavar) in renal cell carcinoma (kidney cancer). Here, patients were classified according to whether they demonstrated evidence of a high blood pressure, which was defined as a systolic blood pressure (the higher number) of 140 or greater, and/or a diastolic blood pressure (the lower number) of 90 or greater over the course of their treatment with sorafenib. The 441 of 534 (83%) who had hypertension had a remarkably higher response rate (54% vs. 10%, p < 0.0001), and a significantly longer median progression-free survival (12.5 vs. 2.5 months, p < 0.0001) and median overall survival (30.5 vs. 7.8 months, p < 0.0001) than the patients with advanced RCC who didn’t have hypertension on the study:
Interestingly, and importantly, the study showed that it didn’t seem to matter much whether patients were treated with a dose reduction of sorafenib, started anti-hypertensive (blood pressure) medicines, or both; the only people who seemed to do poorly were those who never developed high pressure.
Perhaps that’s a fluke, but the same trend has been seen in lung cancer, although without as striking a difference. In a retrospective analysis from the ECOG 4599 trial of carbo/taxol alone or combined with avastin (bevacizumab), patients with high blood pressure on avastin (in this case defined by a much higher bar of a BP above 150 systolic and 100 diastolic) had a median progression-free survivalof 8.0 vs. 4.5 months for those with hypertensive events, while the median overall survival was 14 months, vs. 11.3 months (neither statistically significant). And in a review of a global registry of over 2000 patients receiving avastin in advanced lung cancer that was presented by Dr. Nick Thatcher at the World Conference on Lung Cancer in San Francisco earlier this year (abstract not available), the median overall survival was 18.8 months for those with hypertension, compared with 12. 9 months for those who didn’t show significantly elevated blood pressure.
These are still early reports and represent a small minority of the work being done with anti-angiogenic agents in cancer. Nevertheless, it’s intriguing to see the same trends applying to patients being treated with different anti-angiogenic agents for different cancers, and in several different studies. This issue certainly merits further study and raises the question of whether modifying the dose of anti-angiogenic agents in an attempt to develop high blood pressure, possibly as a biomarker that the drug is acting as intended, may possibly be beneficial. This is not the standard approach right now, but we should see more information about the association of blood pressure and survival with various anti-angiogenic agents in oncology in the coming years.
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Posted on October 22, 2009 at 4:36 pm
My adjuvant treatment mimicked ECOG 1505, featuring maintenance avastin. At about month 7-8 (with NED), I began having problems with hypertension. Also developed proteinuria, but within tolerable limits. BP was deemed too high (~150/100), however, so I began taking Atavan which was effective in reducing the BP. However, my cancer recurrence followed right afterwards at about month 10-11. Coincidence? I have continued the BP medicine even though I have moved on to Tarceva, largely because I am not in the shape I used to be in before all this happened and I was happily training for a marathon. I wonder if I should stop the BP meds at this point.