BARCELONA—In patients with inoperable progressive pancreatic cancer, a targeted radionuclide, lutetium-octreotate (OCLU), shows astir treble the 12-month progression-free endurance (PFS) compared with sunitinib, researchers report.
The findings travel from the signifier 2 OCLURANDOM trial, which investigated the antitumor efficacy of peptide receptor radionucleotide therapy (PRRT) with OCLU successful antecedently treated patients with unresectable progressive pancreatic neuroendocrine tumors (NETs).
It is the archetypal randomized proceedings of PRRT successful patients with advanced, progressive, somatostatin receptor–expressing (SSTR+) pancreatic NETs, the objective trial record says. The 12-month PFS was 80% (33 of 41 patients) successful the OCLU radical vs 42% (18 of 43 patients) successful the sunitinib group.
"This could alteration the signifier attraction paradigm, with PRRT utilized anterior to sunitinib successful unresectable progressive precocious SSTR+ pancreatic NET patients, though ongoing randomized trials enrolling precocious patients volition assistance to corroborate these results," said survey co-investigator David Taïeb, MD, from La Timone Hospital, Aix-Marseille University, Marseille, France, who presented the enactment astatine European Association of Nuclear Medicine (EANM) 2022.
Irene Burger, MD, from Kantonsspital Baden, Switzerland, welcomed the study. "This is simply a tremendous effort, fixed it is simply a main investigator–driven, signifier 2 multicenter study, and tries to adjacent a spread we person successful the denotation to dainty neuroendocrine tumors, due to the fact that pancreatic NETs were not covered successful the NETTER trial, " she said. "Lutetium-DOTATATE [OCLU] is not portion of the guidelines for pancreatic NET aft progression to sunitinib. These archetypal signifier 2 results unfastened the doorway to further studies truthful this volition go a practice-changing therapy enactment for patients," she added.
However, Burger noted that the power limb received sunitinib astatine mean doses and that "this mightiness not beryllium the champion power limb looking up to the signifier 3 study. A higher dose [of] sunitinib mightiness beryllium amended oregon much realistic successful this diligent group."
First Phase 2 Study successful Advanced Unresectable Progressive Pancreatic NETs
Conducted crossed 10 French adept centers, the OCLURANDOM trial, the archetypal of its benignant successful this diligent group, enrolled patients implicit 5 years and had a median follow-up of 40 months. Patients indispensable person had progressive illness implicit the erstwhile 12 months and been antecedently treated with 1 enactment of cytotoxic chemotherapy oregon everolimus oregon somatostatin analogues. Most patients had people 2 oregon 3 pancreatic NETs. More than 25% of patients had liver involvement. The mean diligent property was 63 years, and 52% of patients were female.
Patients were randomly assigned, 1:1, to OCLU (four infusions of 7.4 GBq implicit 8 weeks) oregon sunitinib astatine 37.5 mg/day until progression oregon intolerance. Efficacy was assessed each 12 weeks by computed tomography, and the superior endpoint was the complaint of PFS astatine 1 twelvemonth (according to RECIST 1.1 criteria, real-time blinded).
The secondary endpoints were champion wide tumor response, PFS, wide survival, safety, and prime of life. The proposal was that the OCLU limb would presume a 25–percentage constituent summation (from 35% to 60%) successful the 12-month PFS rate, and if astatine slightest 19 of 40 patients showed nary progression oregon decease astatine 12 months, OCLU would beryllium considered effective, explained Taïeb.
Doubling of PFS With OCLU
Taïeb presented the results, highlighting that the superior endpoint was met with a 12-month PFS complaint of 80.5% (33 of 41 patients) successful the OCLU limb (90% CI, 67.5% - 89.9%) compared with 42% successful 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) successful the OCLU limb compared with 11 months (90% CI, 8.8 - 12.4 months) successful the sunitinib arm. "This effect successful the sunitinib limb replicates what [researchers] recovered — 11.4 months PFS — successful their seminal 2011 trial published successful the NEJM [New England Journal of Medicine]," remarked Taïeb.
"We tin reason that the signifier 2 survey is affirmative and hopefully results are promising," asserted Taïeb.
Regarding the radionuclide cycles, Taïeb reported that 89.5% of patients received 4 cycles; 5.4% successful the OCLU radical stopped attraction due to the fact that of progression compared with 74.4% successful the sunitinib group. "Stopping attraction was uncommon successful the PRRT patients," helium said.
Grade 3 to 4 adverse events occurred successful 45 of the 84 full patients (53%): 18 (44%) successful the OCLU limb and 27 (63%) successful the sunitinib arm. Hematologic events occurred successful 5 and 10 patients successful the OCLU and sunitinib groups, respectively, and were chiefly lymphopenia. Digestive-related adverse effects were observed successful 5 and 9 patients successful each group, respectively.
"These were mostly related to the archetypal amino-acid solution," said Taïeb. Drug withdrawal was required successful 2 patients successful the OCLU limb compared with 9 patients successful the sunitinib arm.
In presumption of semipermanent adverse effects, 1 thymoma, 1 basal compartment carcinoma, and 1 lawsuit of myelodysplastic syndrome (in a diligent antecedently treated with chemotherapy and radiotherapy) occurred successful the OCLU group. One gastrointestinal stromal tumor and 1 lawsuit of myelodysplastic syndrome occurred successful the sunitinib group.
In conclusion, Taïeb said, "this is highest level of grounds successful this population, but further probe is needed to find the optimal sequencing of treatments."
Dr Taïeb declares that helium oregon 1 of his coauthors clasp a presumption arsenic an employee, consultant, assessor, oregon advisor for a pharmaceutical, device, oregon biotechnology institution and that helium oregon 1 of his coauthors person enactment and talker fees from Merck, Viatris, Servier, Pierre Fabre, Oseus, Pfizer, Ipsen, and Novartis.
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