One hundred and one patients with aPDAC were registered on the database. The search process also identified patients with prior VTE either before cancer diagnosis or during adjuvant treatment for PDAC, patients with concurrent diagnosis of TE and aPDAC or patients on long term anticoagulants due to pre-existing AF(atrial Fibrillation) or unprovoked VTE having been switched to an IDPTP schedule (details in Flow chart Figure 1)
Demographics and event rates are reported for the whole cohort but the detailed analyses are restricted to the 82 patients that corresponded to an entirely IDPTP cohort.
The median age was 67 years, interquartile range: 61-72 (n=82) and 54% were male. Sixty five per cent of these patients were metastatic and the rest locally advanced. Ninety-six patients were offered first line chemotherapy. Sixty nine per cent of the patients received only one line of treatment, 20% received two lines of treatment and only 2% received a third line of treatment.
Of the IDPTP cohort (N=82) sixty-four patients (78%) were offered Gemcitabine based first line treatment (48 patients (58%) single agent gemcitabine & 16 (20%) first line gemcitabine-based combination) and 18 patients FOLFIRINOX.
The baseline characteristics of all patients, for the 82 IDPTP patients and the primary endpoint data are shown in Table 1.
In the IDPTP cohort (n=82), patients remained on thromboprophylaxis for a median duration of 8.0 months,95% CI (6.2, 9.7). Seven patients [8.5%, 95%CI (3.7,14.6)] developed a TE despite IDPTP and ten patients [12.2 %, 95%CI (6.1,19.5)] in the IDPTP group had a major bleed and 2 patients [2.4% 95%CI (.0,6.1)] had a minor bleed, for a combined event rate of major bleeding and TE of 18% [n=15/82 as two patients had a TE and a bleed, 95%CI (9.8,26.80)]. The correlation between the IDPTP and the timing of TE and bleeding can be seen in Figure 2. The cumulative rates of MB at 3 and 12 months of this real-world cohort are compared to the experimental arms of FRAGEM and CONKO-04 where data were available (Table 2). Figure 2A&B present the cumulative hazard of developing a breakthrough TE or bleed. The accelerated phase of the cumulative hazards plot is between 4 and 8 months which is later than the conventional first three months seen in patients without thromboprophylaxis, reflecting the median time to TE of 6.2 months (95% CI 10.0, 13.2). This can be seen most clearly in Figure 2C where the data are corrected for competing risk of death. A similar late pattern is noted for the major bleeding episodes median time to MB 4.5 months (95% CI 1.6, 7.4). The majority of the minor and major bleeding events were upper GI (8/14, 57%) and were directly or indirectly attributable to an aPDAC related cause.
Median overall survival time from commencement of IDPTP was 8.7 months, 95%CI, (6.4, 10.9). Neither thrombotic events [12.2 months, 95% CI (10.7, 13.7) Vs 8.4 months, 95% CI (6.9, 9.9) (p = 0.79)] nor bleeding events [median 8.7 months, 95% CI (0.4, 17) Vs 8.4 months, 95% CI (5.8, 11) (p = 0.94)] affected survival outcome. Progressive cancer remained the major cause of death (70 out of 82; 85%) as reported in the death certificate and agreed by the investigators. Five of these patients were found to be suffering from MB as a tumour progression-related event during the process of dying from cancer, the context often informing decision making (e.g. restraint on endoscopic or other invasive procedures or reflection on futility of transfusion). For one patient bleeding (uterine) was reported in the death certificate and confirmed by the investigators as the direct cause of death (1.2%). Two patients suffered a fatal thrombo-embolic event (2.4%). One a CVA and one a pulmonary infarct. Figure 4 charts MB and ATTE in the relevant patients, their timing and their link to the presence or absence of IDPTP over the patient life-span.