BARCELONA—In patients with inoperable progressive pancreatic cancer, a targeted radionuclide, lutetium-octreotate (OCLU), shows nearly double the 12-month progression-free survival (PFS) compared with sunitinib, researchers report.
The findings come from the phase 2 OCLURANDOM trial, which investigated the antitumor efficacy of peptide receptor radionucleotide therapy (PRRT) with OCLU in previously treated patients with unresectable progressive pancreatic neuroendocrine tumors (NETs).
It is the first randomized trial of PRRT in patients with advanced, progressive, somatostatin receptor–expressing (SSTR+) pancreatic NETs, the clinical trial record says. The 12-month PFS was 80% (33 of 41 patients) in the OCLU group vs 42% (18 of 43 patients) in the sunitinib group.
“This could change the practice treatment paradigm, with PRRT used prior to sunitinib in unresectable progressive advanced SSTR+ pancreatic NET patients, although ongoing randomized trials enrolling advanced patients will help to confirm these results,” said study co-investigator David Taïeb, MD, from La Timone Hospital, Aix-Marseille University, Marseille, France, who presented the work at European Association of Nuclear Medicine (EANM) 2022.
Irene Burger, MD, from Kantonsspital Baden, Switzerland, welcomed the study. “This is a tremendous effort, given it is a principal investigator–driven, phase 2 multicenter study, and tries to close a gap we have in the indication to treat neuroendocrine tumors, because pancreatic NETs were not covered in the NETTER trial, ” she said. “Lutetium-DOTATATE [OCLU] is not part of the guidelines for pancreatic NET after progression to sunitinib. These first phase 2 results open the door to further studies so this will become a practice-changing therapy option for patients,” she added.
However, Burger noted that the control arm received sunitinib at normal doses and that “this might not be the best control arm looking ahead to the phase 3 study. A higher dose [of] sunitinib might be better or more realistic in this patient group.”
First Phase 2 Study in Advanced Unresectable Progressive Pancreatic NETs
Conducted across 10 French expert centers, the OCLURANDOM trial, the first of its kind in this patient group, enrolled patients over 5 years and had a median follow-up of 40 months. Patients must have had progressive disease over the previous 12 months and been previously treated with one line of cytotoxic chemotherapy or everolimus or somatostatin analogues. Most patients had grade 2 or 3 pancreatic NETs. More than 25% of patients had liver involvement. The mean patient age was 63 years, and 52% of patients were female.
Patients were randomly assigned, 1:1, to OCLU (four infusions of 7.4 GBq over 8 weeks) or sunitinib at 37.5 mg/day until progression or intolerance. Efficacy was assessed every 12 weeks by computed tomography, and the primary endpoint was the rate of PFS at 1 year (according to RECIST 1.1 criteria, real-time blinded).
The secondary endpoints were best overall tumor response, PFS, overall survival, safety, and quality of life. The hypothesis was that the OCLU arm would assume a 25–percentage point increase (from 35% to 60%) in the 12-month PFS rate, and if at least 19 of 40 patients showed no progression or death at 12 months, OCLU would be considered effective, explained Taïeb.
Doubling of PFS With OCLU
Taïeb presented the results, highlighting that the primary endpoint was met with a 12-month PFS rate of 80.5% (33 of 41 patients) in the OCLU arm (90% CI, 67.5% – 89.9%) compared with 42% in patients receiving sunitinib (18 of 43 patients with 12-month PFS) (90% CI, 29.1% – 55.5%).
Median PFS duration was 20.7 months (90% CI, 17.2 – 23.7 months) in the OCLU arm compared with 11 months (90% CI, 8.8 – 12.4 months) in the sunitinib arm. “This result in the sunitinib arm replicates what [researchers] found — 11.4 months PFS — in their seminal 2011 trial published in the NEJM [New England Journal of Medicine],” remarked Taïeb.
“We can conclude that the phase 2 study is positive and hopefully results are promising,” asserted Taïeb.
Regarding the radionuclide cycles, Taïeb reported that 89.5% of patients received four cycles; 5.4% in the OCLU group stopped treatment because of progression compared with 74.4% in the sunitinib group. “Stopping treatment was rare in the PRRT patients,” he said.
Grade 3 to 4 adverse events occurred in 45 of the 84 total patients (53%): 18 (44%) in the OCLU arm and 27 (63%) in the sunitinib arm. Hematologic events occurred in 5 and 10 patients in the OCLU and sunitinib groups, respectively, and were mainly lymphopenia. Digestive-related adverse effects were observed in 5 and 9 patients in each group, respectively.
“These were mostly related to the initial amino-acid solution,” said Taïeb. Drug withdrawal was required in 2 patients in the OCLU arm compared with 9 patients in the sunitinib arm.
In terms of long-term adverse effects, one thymoma, one basal cell carcinoma, and one case of myelodysplastic syndrome (in a patient previously treated with chemotherapy and radiotherapy) occurred in the OCLU group. One gastrointestinal stromal tumor and one case of myelodysplastic syndrome occurred in the sunitinib group.
In conclusion, Taïeb said, “this is highest level of evidence in this population, but further research is needed to determine the optimal sequencing of treatments.”
Dr Taïeb declares that he or one of his coauthors hold a position as an employee, consultant, assessor, or adviser for a pharmaceutical, device, or biotechnology company and that he or one of his coauthors receive support and speaker fees from Merck, Viatris, Servier, Pierre Fabre, Oseus, Pfizer, Ipsen, and Novartis.
European Association of Nuclear Medicine (EANM) 2022. Presented October 16, 2022.
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