Results of the randomized, open-label phase 2 Australasian Gastrointestinal Trials Group CONTROL NET study indicate that capecitabine/temozolomide (CAPTEM) plus 177Lu-octreotate peptide receptor radionuclide therapy (PPRT) combination treatment was active and well-tolerated compared with CAPTEM or PPRT alone in patients with pancreatic neuroendocrine tumors (pNETs) and updated midgut neuroendocrine tumors (mNETs).
The phase 2 Australasian Gastrointestinal Trials Group CONTROL NET study is evaluating the addition of CAPTEM to the standard LuTate PRRT platform in patients with pNETs and updated mNETs; initial results of this trial were reported at the 2020 American Society of Clinical Oncology Virtual Scientific Program.
This single-center, noncomparative, randomized, open-label, parallel-group trial consists of 2 cohorts (2 different controls for each cohort): cohort A, low-to-intermediate grade pNETs (control: CAPTEM); cohort B, low-to-intermediate grade mNETs (control: PRRT). Eligibility criteria include adults with histologically proven, moderate to well-differentiated, unresectable grade 1/2 pNETs or mNETs with presence of somatostatin receptor avidity suitable for PRRT, advanced metastatic disease that has progressed during or after ≤2 prior therapies, or previously untreated advanced metastatic disease with high symptomatic burden and nonfunctional tumors for which other therapies are not indicated or appropriate. Eligible patients were randomized 2:1 to receive CAPTEM-PRRT versus CAPTEM in the pNETs cohort and versus PRRT in the mNETs cohort. The primary end point was progression-free survival (PFS); secondary end points were objective tumor response rate, clinical benefit rate, toxicity, and quality of life.
A total of 75 patients were enrolled in the trial from December 2015 to November 2018; of these, 28 patients were enrolled in the pNETs cohort (PRRT/CAPTEM, 19; CAPTEM, 9) and 47 patients were enrolled in the mNETs cohort (PRRT/CAPTEM, 33; PRRT, 14). At a median follow-up of 33.8 months in the pNETs cohort, 12-month PFS was 75.9% (95% confidence interval [CI], 48%-90%) with CAPTEM/PRRT compared with 66.7% (95% CI, 28%-88%) with CAPTEM; the ORR was also numerically higher (67% vs 33%) with the CAPTEM/PRRT regimen. In the mNETs cohort, 15-month PFS was 90% (95% CI, 73%-97%) with CAPTEM/PRRT compared with 92% (95% CI, 57%-99%) with PRRT; the ORR was numerically higher (31% vs 15%) with the CAPTEM/PRRT regimen.
The incidence of grade 3/4 treatment-related adverse events was similar between the experimental and control groups in the pNETs cohort (44% vs 44%), whereas the incidence rate was nearly double that of the control arm in the experimental arm in the mNETs cohort (88% vs 46%); the majority of these events were hematologic in nature.
These initial results indicate that the CAPTEM/PRRT regimen was active and met its target landmark PFS for CAPTEM/PRRT with numerically higher ORRs in both pNETs and mNETs.
Source: Pavlakis N, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4608.
