ClinicalTrials.gov, number NCT00544700.

No abstract

Background: Antiangiogenic therapy is routinely used in a variety of cancer entities. Hypertension is the most common side effect of all currently available antiangiogenic treatments. Patients and Methods: In this prospective observational clinical trial, we investigated risk factors for blood pressure elevation in patients exposed to an antiangiogenic agent and explored the correlation between hypertension and the duration of antiangiogenic treatment. Results: In 169 patients, pre-existing antihypertensive medication was the most prominent risk factor associated with increased blood pressure during therapy. Between visits 1 and 3, the median systolic blood pressure increased by 10.85 mmHg in patients with pre-existing hypertension receiving antihypertensive medication while it increased by only 2.69 mmHg in patients without hypertension. The median increase in diastolic pressure was 7.28 versus 0.11 mmHg in patients with versus without pre-existing hypertension. Increases in blood pressure occurred early (within 6 weeks of starting therapy). In spite of this significant increase in the blood pressure, no major bleeding events or other related complications were observed during antiangiogenic therapy. Conclusions: Pre-existing hypertension and treatment with antihypertensive medication correlated with a more pronounced increase in blood pressure. Thus, intensified antihypertensive therapy might be warranted early during bevacizumab therapy in patients already receiving antihypertensive treatment.

3503 Background: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after stop of first-line chemotherapy. Methods: In an open-label, phase 3 multicenter study conducted in Switzerland, patients with unresectable metastatic colorectal cancer having non-progressive disease after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned in a 1:1 ratio to continuing bevacizumab (7.5 mg/kg every 3 weeks) or no treatment. CT scans were done every 6 weeks between randomization and disease progression. The primary endpoint was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significant level of 10% and a statistical power of 85%. Results: The per-protocol population comprised 262 patients. Median follow-up is 28.6 months (range, 0.6-54.9 months). Median TTP was 17.9 weeks (95% CI 13.3-23.4) for bevacizumab continuation and 12.6 weeks (95% CI 12.0-16.4) for no continuation; HR 0.72 (95% CI 0.56-0.92). Median progression free-survival and overall survival, both measured from start of first-line treatment, was 9.5 months and 24.9 months for bevacizumab continuation and 8.5 months (HR 0.73 (95% CI 0.57 - 0.94)) and 22.8 months (HR 0.87 (95% CI 0.64 – 1.18)) for no continuation. Median time from randomization to second-line treatment was 5.9 months for bevacizumab and 4.8 for no continuation. Grade 3-4 adverse events in the bevacizumab continuation arm were uncommon. Conclusions: Non-inferiority could not be demonstrated. The 95% confidence intervals for the TTP HR indicate superiority of bevacizumab continuation after stop of first-line chemotherapy. The median differences in TTP and in time between randomization and start of second-line treatment were of moderate magnitude being less than 6 weeks. The results of an accompanying cost analysis will be presented at the meeting. Clinical trial information: NCT00544700.

269 Background: TTFields are alternating electric fields delivered to the region of the tumor by means of non-invasive transducer arrays. TTFields interfere with mitotic spindle formation, thus having an anti-mitotic activity. In pancreatic cancer, TTFields decreased proliferation and clonogenic potential in vitro, and reduced tumor volume in vivo. The PANOVA trial was designed to test TTFields, combined with chemotherapy, in pancreatic cancer. Methods: Twenty patients with advanced pancreatic adenocarcinoma were enrolled in a prospective, single arm study of TTFields at 150 kHz, concomitant with standard weekly gemcitabine. All patients had histologically-confirmed unresectable tumors, with an ECOG performance score of 0-1 and no prior chemotherapy or radiation therapy. The primary endpoint was incidence and severity of treatment emergent adverse events (AEs). Secondary endpoints included progression free survival (PFS), PFS rate at 6 months, overall survival (OS) and response rate. Results: The median age was 73 (range – 49-81) and 60% of the patients were females. Most patients (80%) had an ECOG score of 1. Twelve patients (60%) had distant metastases, while the others had locally advanced disease. Median compliance with TTFields was 78% (14 hours/day), with median duration of 5 months. Fourteen patients (70%) had serious (grade 3-5) AEs during the study period. Six patients (30%) had hematological, 45% gastrointestinal and 15% pulmonary AEs. Ten patients (50%) had treatment-related skin toxicity, of which only 2 were grade 3, both resolved with appropriate treatment. No TTFields-related serious AEs were reported. The median PFS was 8.3 months (95% CI 4.3, 10.3). PFS rate at 6 months was 56%. Of the evaluable tumors, 30% had partial response and another 30% stable disease. The median OS was 14.9 months and 1-year survival rate was 55%. Conclusions: TTFields concomitant to gemcitabine are tolerable and safe for advanced pancreatic cancer patients. The efficacy results are promising and support further research in this indication. An extension of the PANOVA protocol, including 20 additional patients who receive gemcitabine, nab-paclitaxel and TTFields is ongoing. Clinical trial information: NCT01971281.