tients and 366 and 268 days, respectively, for patients treated with the other agents. Among 104 RCC patients treated solely with pazopanib following the index date (Table 2), 13 total events occurred among 10 patients as follows: five CVA events 4.8% (95% CI: 1.6-10.9%), three events each of MI and TIA 2.9%, (95% CI: 0.6-8.20%, and one event each of TP and UA 1.0% (95% CI: 0.02- 5.2%). The median time to event among pazopanib-only patients was shortest for the five CVA events (29 days) and longest for patients experiencing a TP event (580 days). In comparison, the incidence proportions for cardiovascular events among the Table 1. Characteristics of RCC patients treated with single agent or multiple anti-VEGF therapy, stratified by cardiovascular event after study index date (IMPACT database). CV Event CV Event after Study in Year Prior Median Age, Index N (%) to Index (%) Male (%) years Pazopanib Only No 94 (90%) 13% 74% 61 (n=104) Yes 10 (10%) 40% 50% 64 Bevacizumab Only No 79 (92%) 15% 66% 65 (n=86) Yes 7 (8%) 0 71% 63 Sorafenib Only No 71 (85%) 10% 80% 61 (n=84) Yes 13 (15%) 38% 92% 65 Sunitinib Only No 357 (92%) 6% 71% 59 (n=386) Yes 29 (8%) 14% 79% 62 Multiple: Pazopanib first No 20 (91%) 10% 65% 58 (n=22) Yes 2 (9%) 0 100% 63 Multiple: Pazopanib not first No 79 (79%) 8% 68% 60 (n=100) Yes 21 (21%) 24% 71% 58 Multiple: no Pazopanib No 50 (93%) 8% 60% 61 (n=54) Yes 4 (7%) 50% 50% 78 comparator group with users of one other anti-VEGF drug (n=556) were: CVA 2.2% (95% CI: 1.1-3.7%), MI 4.5% (95% CI: 2.9-6.6%), TIA 1.4% (95% CI: 0.6-2.8%), TP 1.6% (95% CI: 0.7-3.1%), UA 1.6% (95% CI: 0.7-3.1%). Among the comparator group using only one drug, the shortest median time to event was observed among patients experiencing a TIA event (96 days); the longest median time to event was found for UA events (337 days). The majority (69%) of the comparator Abbreviations: cardiovascular (CV), renal cell carcinoma (RCC), vascular endothelial growth factor (VEGF). group was comprised of sunitinib-only users and most cardiovascular events (38/63, 60%) were observed among patients treated with sunitinib only. However, the highest incidence proportion observed among non-pazopanib users with only one line of therapy was found for MI events in patients treated only with sorafenib 8/84, 9.5% (95% CI: 4.2-17.9%). The incidence proportions for cardiovascular events occurring in RCC patients treated with multiple anti- VEGF therapies are shown in Table 3. Events are listed by the anti-VEGF therapy that was taken closest prior to or at the time of the cardiovascular event; the denominator is comprised of all subjects who received each therapy either prior to another therapy (first line) or following another therapy (second line or higher). Among first line pazopanib patients (n=22), no events occurred. Nine events were observed among patients treated with pazopanib in the second line or higher setting (n=100), 5 CVA events 5% (95% CI: 1.6-11.3%) and one event each for MI, TIA, TP and UA 1% (95% CI: 0.03-5.5%). Results for the other anti-VEGF agents used in the first or second line setting were similar. In the PHARMO Database Network, a total of 21 pazopanib 46 Kidney Cancer Journal users, 6 sorafenib users, and 90 sunitinib users met the eligibility criteria. One pazopanib patient had a CVA event and one sunitinib user experienced a UA event; no other outcomes were observed during the study period data not shown. These patient and event numbers were too low to perform incidence analyses. Discussion The analyses from this descriptive study indicate that the cardiovascular events under investigation occurred in 0- 9.5% of RCC patients treated with pazopanib or other anti-VEGF agents. To our knowledge, population-based estimates for these outcomes in pazopanib users do not exist. Cardiac or cerebral ischemic events were rare, but occurred in clinical trials of pazopanib among patients with advanced RCC.7-9 In the pivotal phase III trial, arterial thrombotic events consisting of MI, CVA or TIA occurred in 3% of patients receiving pazopanib compared to none in the placebo arm.10 A recent meta-analysis of arterial thrombotic events in patients from 19 randomized controlled trials of cancer patients treated with anti-VEGF drugs, including pazopanib, reported an overall incidence proportion of 1.5%; cardiac infarction/ischemia was the most common event type.11 Considering the low survival rates associated with advanced metastatic RCC, it is possible that mortality is a competing risk with non-fatal events observed only among survivors. This study is primarily focused on pa-
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