Cárdenes, Higinia R.

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

4627 Background: E4201 compared radiation and gemcitabine (RT+Gem) versus Gem alone in LAPC. The primary endpoint was overall survival; secondary objectives included: objective response rate (RR), progression-free survival (PFS), toxicity and QOL. We previously reported that RT+Gem was associated with improved overall survival compared with Gem alone [median survival time, 11 months and 9.2 months, respectively; p=0.034], without impact in RR or PFS. (ASCO 2008, abstract # 4506). We now report on QOL as measured by the Hep subscale from the FACT-Hepatobiliary [FACT-Hep] between both arms. Methods: Eligible patients had LAPC adenocarcinoma, PS <2, without prior therapy. They were randomized to Arm A: Gem alone (1,000 mg/m2/week x 3, every 4 weeks, 7 cycles), or Arm B: RT (50.4Gy/28 fractions) plus Gem (600 mg/m2/weekly x 6) followed by 5 cycles of Gem alone (1,000 mg/m2/weekly x 3 every 4 wks). The FACT-Hep was administered at baseline (before starting induction), 6 weeks (immediately after completing induction), week 16 (Arm A) or week 15 (Arm B) mid-consolidation, and at 9 months. Results: From April, 2003 to December, 2005, 74 patients were enrolled, 71 were eligible [37 Arm A; 34 Arm B]. Grade ≥3 was reported in 80% and 82.4% in ARM A and B, respectively (p=1.00). Grade IV toxicities, mainly gastrointestinal and hematologic, were more common in ARM B (41.2% vs 5.7%, p=<0.0001). QOL compliance declined over time, most commonly attributable to either patients or staff choosing not to complete or administer the instrument due to declining health (96%, 69%, 60%, and 40% at baseline, week 6, 15/16 weeks and 9 months, respectively). Within Arm B, QoL scores dropped significantly from baseline to 6 weeks. By week 15, QoL scores for patients on Arm B rebounded to levels similar to baseline. Two-sided Wilcoxon rank sum tests failed to suggest differences in median FACT-Hep subscale score between treatment arms at any of the four time-points (alpha = 0.10). Conclusions: RT+Gem is associated with an overall survival benefit without apparent long term adverse impact on QOL when compared with Gem alone. No significant financial relationships to disclose.

Purpose The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine (GEM) compared with GEM alone in patients with localized unresectable pancreatic cancer. Patients and Methods Patients with localized unresectable adenocarcinoma of the pancreas were randomly assigned to receive GEM alone (at 1,000 mg/m 2 /wk for weeks 1 to 6, followed by 1 week rest, then for 3 of 4 weeks) or GEM (600 mg/m 2 /wk for weeks 1 to 5, then 4 weeks later 1,000 mg/m 2 for 3 of 4 weeks) plus radiotherapy (starting on day 1, 1.8 Gy/Fx for total of 50.4 Gy). Measurement of quality of life using the Functional Assessment of Cancer Therapy–Hepatobiliary questionnaire was also performed. Results Of 74 patients entered on trial and randomly assigned to receive GEM alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4 toxicities combined were similar (77% in A v 79% in B). No statistical differences were seen in quality of life measurements at 6, 15 to 16, and 36 weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to 11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B, respectively (one-sided P = .017 by stratified log-rank test). Conclusion This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer, with acceptable toxicity.