Ubat kanser Avastin atau Bevacizumab menyebabkan
pesakit kanser mati lebih cepat
Avastin Boosts death risk in cancer patients
Bevacizumab Boosts Stroke and MI Risk in Metastatic
Cancer
SOUTH SAN FRANCISCO, Aug. 7 -- When bevacizumab
(Avastin) is added to chemotherapy for metastatic cancer it raises the risks of
heart attacks, strokes, and other arterial thromboembolic events, found
researchers here.
In a pooled retrospective analysis
of suggestive safety data from five Genentech-sponsored individual trials,
combination therapy with bevacizumab doubled the risk of thromboembolic events
compared with chemotherapy alone (P=0.031), found
Frank A. Scappaticci, M.D., Ph.D., of Genentech here, and colleagues.
Despite these risks, bevacizumab is
still beneficial for overall and progression-free survival in metastatic
cancer, Dr. Scappaticci and colleagues said in the Aug. 15 issue of the Journal of the National Cancer Institute. Physicians
should consider the risk for individual patients, they wrote.
The analysis included trials that randomized a total
of 1,745 patients with metastatic colorectal cancer, breast cancer, or
non-small-cell lung cancer to treatment with bevacizumab plus chemotherapy or with
chemotherapy alone.
Nearly all patients (94%) were given 5-FU- (Adrucil)
or capecitabine- (Xeloda) based chemotherapy.
The researchers identified 13 events in the control
group and 37 in the combination therapy group by searching study databases for
angina, arterial thrombosis, cerebral infarct or ischemia, MI, cerebrovascular
accident, and myocardial ischemia. Most events were MI (or angina) or stroke
(or transient ischemic attack).
The addition of bevacizumab increased the
arterial thromboembolic event rate from 1.7% for chemotherapy alone to 3.8%
(difference 2.1%, 95% confidence interval 0.7% to 3.7%) for a doubling in risk
(hazard ratio 2.0, P=0.031).
The absolute rate similarly increased
1.8-fold with bevacizumab, though this was not a statistically significant
difference (5.5 events per 100 person-years of exposure versus 3.1 for
chemotherapy alone, P=0.076).
Thirty-day
mortality from arterial thromboembolic events was likewise elevated among
bevacizumab-treated patients (0.62% versus 0.26% among controls).
Venous thromboembolism -- although
substantially more common at almost 10% of patients -- did not show the same
pattern of elevated risk. The occurrence rate of grade 3 or 4 venous
thromboembolic events was comparable between groups (9.97% with bevacizumab
versus 9.85% without it, HR 0.89, P=0.44).
They
calculated point estimates of benefit accounting for thromboembolic risk in one
of the colorectal cancer trials and found "clinically and statistically
significant improvements" for the bevacizumab combination compared with
chemotherapy alone.
Tumor
progression events were less common with bevacizumab plus chemotherapy than
with chemotherapy alone (HR 0.54, 95% CI 0.45 to 0.66) as were events impacting
overall survival (HR 0.66, 95% CI 0.54 to 0.81).
Adjusting
for arterial thromboembolic events eliminated the overall benefit for the
subgroup of patients ages 65 or older with a prior arterial thromboembolic
event (HR 0.55 for progression-free survival, 95% CI 0.22 to 1.37, and 0.59 for
overall survival events, 95% CI 0.27 to 1.28).
"Nevertheless,
the point estimates of benefit in this group were consistent with the overall
population," the researchers said, leading them to conclude, "the
risks and benefits for bevacizumab treatment were consistent across all
subgroups examined."
In multivariate analysis, these patient
groups were also at significantly elevated risk of arterial thromboembolic
events (P<0.001 for
prior arterial thromboembolic event and P=0.01
for age 65 or older).
Subgroup analyses showed the same trend,
though not significant, in rates for older patients (4.7 per 100 person-years
for controls versus 10.0 with bevacizumab, P=0.082), those with a history of arterial
thromboembolic (5.9 versus 24.4, P=0.060),
and those with both risk factors (3.6 versus 27, P=0.052).
The
concomitant use of bevacizumab, chemotherapy, and aspirin did not appear to
substantially increase the risk of serious bleeding compared with the use of
aspirin and chemotherapy alone. In addition, the small number of arterial
thromboembolic events and also of aspirin users in our study did not allow
definitive conclusions about the prophylactic benefit of aspirin.
However,
they pointed out that "the use of low-dose aspirin for the prophylaxis of
arterial thromboembolic events in high-risk patients is supported by an
extensive body of literature and is a recommended standard of care."
"Aspirin-based
prophylaxis for an arterial thromboembolic event should be carefully considered
for individual patients with metastatic adenocarcinoma who are at high risk for
an arterial thromboembolic event and who have no contraindications for aspirin
use," the researchers concluded.
They
cautioned that the raw incidence rates in their analyses may overestimate risks
with bevacizumab "because of the delayed time to progression and
correspondingly longer safety observation period" for combination therapy
patients.
But,
they also noted that the study did not consider functional disabilities caused
by these events and did not include patients with stroke or MI in the year
prior to trial enrollment.
Other
important clinical questions remain as well, the investigators wrote. These
include whether arterial thromboembolic risk varies by tumor type, different
chemotherapy agents when combined with bevacizumab, or other disease settings
(such as adjuvant treatment).
Nevertheless,
the findings will be useful for clinicians who treat patients with metastatic
cancer, they concluded.
"The
risk factors for arterial thromboembolism should be considered when making
treatment decisions for individual patients," they wrote.
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