Efficacy and safety by tumor location in the phase 3 PANOVA-3 trial of Tumor Treating Fields (TTFields) with gemcitabine/nab-paclitaxel in locally advanced pancreatic adenocarcinoma.

Abstract

e16367 Background: Outcomes of unresectable, locally advanced pancreatic adenocarcinoma (LAPAC) remain poor, with therapy based mainly on data from trials in metastatic disease. TTFields use alternating electric fields to disrupt cancer cell proliferation. The phase 3 PANOVA-3 trial (NCT03377491) demonstrated that TTFields with gemcitabine/nab-paclitaxel (GnP) significantly improved overall survival (OS; HR 0.82) and pain-free survival (HR 0.74) vs GnP in patients with unresectable LAPAC. We report an analysis of efficacy and safety in PANOVA-3 by tumor location. Methods: Patients with newly diagnosed LAPAC were randomized 1:1 to receive GnP with or without concomitant TTFields. Kaplan-Meier methodology was used for time-to-event analyses. Response evaluations were based on RECIST V1.1. OS and pain-free survival were analyzed post-hoc without stratification in patient subgroups with tumors in the head, body, and tail of pancreas. Differences between treatment arms were compared using a 2-sided log-rank test. Results: Tumors were located in: head of pancreas, n=163 and 158 in the TTFields + GnP and GnP arms, respectively; body of pancreas, n=81 and 79; tail of pancreas, n=9 and 19. Baseline characteristics were generally similar in the TTFields + GnP and GnP arms in each subgroup, with the exception of gender (male: head 51.5% vs 41.1%; body 45.7% vs 48.1%; tail 88.9% vs 52.6%). Median OS was 15.8 (12.7, 18.0) vs 12.9 (11.5, 15.4) months in the TTFields + GnP and GnP arms in the head of pancreas subgroup; 18.6 (95% CI: 15.7, 22.5) vs 16.4 (13.1, 20.1) months in the body of pancreas subgroup; and 13.9 (3.0, 17.1) vs 14.9 (11.5, 18.7) months in the tail of pancreas subgroup (all P>0.05). Median pain-free survival was 10.2 (6.6, 16.5) vs 7.6 (5.9, 9.5) months, 18.7 (11.0, NE) vs 9.3 (6.6, 16.3) months (P=0.041), and 5.4 (1.2, NE) vs NE (4.5, NE) months, respectively, in these subgroups (P>0.05 unless otherwise stated). The type and incidence of device-related adverse events (AEs) were comparable. Conclusions: In this post-hoc subgroup analysis with small sample sizes, median OS and pain-free survival were consistent with the primary analysis of the overall population. These data support the use of TTFields with GnP in unresectable LAPAC regardless of tumor location. Clinical trial information: NCT03377491 .