Pazopanib in Patients with Progressive Recurrent or Metastatic (R/M) Salivary Gland Carcinoma (SGC): Further Evaluation of Efficacy Including Tumor Growth Rates (GR) Analysis. H&N Unicancer Group PACSA Trial with the REFCOR

SGC of head and neck (SGCHN) are rare tumors including adenoid cystic carcinoma (ACC) and non-ACC, with no standard treatment for R/M patients (pts). Pazopanib (Pb) is an oral inhibitor of VEGFR, PDGFR and KIT. We conducted a phase II trial to assess Pb efficacy in SGCHN, and present here results of the ancillary GR study. Pts with confirmed progressive R/M SGCHN received Pb 800 mg daily until progression (PD). Primary endpoint was 6-mo PFS rate, with inacceptable and promising rates of 20% and 40%. Tumor volumes were assessed with a medical imaging workstation (Advantage Workstation, GE Healthcare) Assuming exponential growth, GR was defined as log10(Vt/V0)/dt, where V0 and Vt are tumour volumes at time 0 and t and dt the time in months between time 0 and t. Two time periods: pretrial period, from 3-6 mo before inclusion to inclusion (GRpre) and trial period, from inclusion to 3 mo later (GRpost). GR variation was defined as the difference GRpost minus GRpre., a negative difference means a GR break (GRpost < GRpre). GRpost < 0 means a tumor volume decrease. From 2013 to 2015, 72 pts were enrolled: 49 ACC and 20 non-ACC (3 ineligible excluded), M:F = 32:37, median age 59 yrs (range 27-84), PS 0-1 = 42:27. Pb tolerance was as expected. Among 63 pts (45 ACC, 18 non-ACC) evaluable for efficacy (6 non progressive excluded), 6-mo PFS rate was 47% (95%CI = 36;60) with 30 pts without PD at 6 mo, median PFS was 5.9 mo. Median OS was 17 mo. The 6-mo PFS met the criteria for efficacy conclusion of the trial. GR study was performed among 31 patients (24 ACC, 7 non-ACC). 6-mo PFS was 61% [IC95%:43;76] with 19 pts without PD at 6 mo. Median PFS was 8.2 mo. GR variation analysis showed a significant GR break 3 mo after Pb start (median -0.06 (range -0.37; + 0.10) p < 0.0001) with 26 pts (84% [IC95%:66;95]) having a GR break. 15 pts (48% [IC95%: 30;67]) had a volume decrease after Pb start. GRpre and GR variation were not associated with PD at 6 mo. There is a significant decrease in GR between evaluations done before inclusion and 3 months after Pb start, i.e. a break in tumor growth rate, in agreement with the PFS based conclusion of promising efficacy of Pb in R/M SGCHN.