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Jaume Capdevila, MD, PhD, discusses the potential for 177Lu-edotreotide for the treatment of patients with neuroendocrine tumors.
As radioligand therapies continue to evolve for the management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), data from the phase 3 COMPETE trial (NCT03049189) underscore the potential for 177Lu-edotreotide (ITM-11) to redefine standards of care for this population, according to Jaume Capdevila, MD, PhD.1,2
Primary end point data from the trial, presented at the 2025 ESMO Congress, showed that by central assessment, the median progression-free survival (PFS) was 23.9 months (95% CI, 18.7-30.0) with 177Lu-edotreotide (n = 207) vs 14.1 months (95% CI, 9.2-20.9) with everolimus (Afinitor; n = 102; HR, 0.67; 95% CI, 0.48-0.95; P = .022). Local investigator assessment showed consistent results, with a median PFS of 24.1 months (95% CI, 21.2-26.7) in the 177Lu-edotreotide arm vs 17.6 months (95% CI, 12.2-21.0) in the everolimus arm (HR, 0.66; 95% CI, 0.48-0.91; P = .010).
Key Findings: COMPETE Trial
Subgroup analyses of PFS by tumor origin demonstrated numerically longer outcomes for both gastrointestinal NETs (GE-NETs) and pancreatic NETs (P-NETs) in the 77Lu-edotreotide arm compared with the everolimus arm. Among patients with GE-NETs, the median PFS was 23.9 months (95% CI, 14.0-not evaluable [NE]) with 177Lu-edotreotide (n = 88) vs 12.0 months (95% CI, 8.8-23.7) with everolimus (n = 43; HR, 0.64; 95% CI, 0.38-1.08; P = .090). In patients with P-NETs, the median PFS was 24.5 months (95% CI, 18.4-30.0; n = 119) vs 14.7 months (95% CI, 8.5-NE; n = 59), respectively (HR, 0.70; 95% CI, 0.45-1.09; P = .114).
In an interview with OncLive® at ESMO 2025, Capdevila discussed the pivotal efficacy and safety findings from the COMPETE trial, the role of 177Lu-edotreotide in optimizing disease control and quality of life, and how these data may inform the sequencing of radioligand therapy within the broader treatment paradigm for patients with advanced GEP-NETs.
“Altogether, my humble opinion is that COMPETE is a real practice-changing study, and [its regimen] is easy to implement in clinical practice,” he explained.
Capdevila serves as a medical oncologist and head of the Endocrine Tumors and Sarcomas Unit at Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain.
Capdevila: We presented the main secondary end points: overall survival [OS] and overall response rate [ORR]. For OS, we have a positive trend [favoring 177Lu-edotreotide], but it’s immature, so we need a longer follow-up. For ORR, 177Lu-edotreotide shows a significant improvement in the probability of having a partial response compared with everolimus: [3.9]% for everolimus [vs 19.3]% for 177Lu-edotreotide. This has been shown by the central radiology assessment, which is the main secondary end point, but [similar results were seen] by investigators. Local assessments showed the same trend in improvement of ORR.
The design of the study [was based on] the idea [of] reducing long-term toxicity by applying the radiopharmaceutical every 3 months instead of every 2 [months], as we know from other phase 3 studies with other radioligands. It’s interesting that we showed less general toxicity with 177Lu-edotreotide compared with everolimus, except for bone marrow toxicity, which was expected because this is one of the typical adverse effects [AEs] of radioligand therapies. That being said, only 1.8% of the patients [n = 4] needed to stop therapy due to AEs associated with 177Lu-edotreotide; approximately 3 of them [discontinued] due to low thrombocyte count, and the other [patient discontinued due to increased creatinine] levels. [In contrast, discontinuation with everolimus was required due to AEs in 15.2% of patients, which was statistically significant.]
Another important point is that we did not observe any leukemia, which is one of the main concerns associated with radioligand agents over the long term. We have more than 40 months of follow-up, and no cases of leukemia were observed, with only 1 [case of] myelodysplastic syndrome [MDS]. [When compared] with prior phase 3 studies, [in which] approximately 3% of patients developed MDS or leukemias, it seems that delaying these doses to every 3 months instead of every 2 months may have an effect on the safety of the drug.
I believe that COMPETE is a practice-changing study. We have several points here to consider now. The first is that we are treating patients who are most frequently seen in the office, [not only] those who are progressing on somatostatin analogs upfront. Second-line everolimus vs [PRRT] here makes more sense than moving that therapy earlier or to later lines.
We also showed that concomitant therapy with somatostatin analogs is not needed, and this is something different compared with [findings from] other phase 3 studies. Here, 177Lu-edotreotide was only allowed to be used with somatostatin analogs at the same time for functioning tumors. All the other patients were treated without analogs, and this [reduced] toxicity for patients in the long term and is also more economically feasible.
We are also showing data on [PRRT’s] effect in low-grade pancreatic NETs, and this is the first time that this has been shown in a prospective phase 3 study. [By spacing] the doses further apart—every 3 months instead of every 2—we have seen less long-term bone marrow toxicity.
We have a lot of [remaining] questions to answer. [With] radioligands, after several years when NETs were almost nowhere on the map, now everyone wants to replicate what we are doing in this disease. We now have a lot of experience with radioligands, so we are looking [to determine] what the next step [for developing these agents] is.
Beta emitters are [in the paradigm], and we are positioning beta emitters in earlier lines within the guidelines, but patients will eventually experience progression. How do we treat these patients after progression on beta emitters? We may consider [retreatment] with beta emitters, or we may need to position alpha emitters. We also need to explore combinations or strategies between treatments to allow more time for bone marrow recovery and to further reduce the risk of MDS.
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