90Y-edotreotide for metastatic carcinoid refractory to octreotide

Abstract

Purpose: Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using (90)Y-edotreotide to treat symptomatic patients with carcinoid tumors.

Patients and methods: Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) (90)Y-edotreotide each, once every 6 weeks.

Results: Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days.

Conclusion: (90)Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile.

Fig 1.

(A) Kaplan-Meier analyses for patients with durable diarrhea response, no durable response, and those without diarrhea at baseline. The median time for progression-free survival (PFS) in these groups was 18.2, 7.9, and 17.0 months, respectively. (B) A landmark approach was used to analyzed PFS at 6 months, with 51 patients stratified by presence of a durable response before 6 months. Only patients who were progression free through 6 months were included in the analysis. At 6 months, patients were dichotomized by whether they had durable improvement in diarrhea symptoms before 6 months. neg, negative; pos, positive; asym, asymmetrical.

Fig 2.

(A) Pretherapy (baseline) and follow-up T2 weighted axial magnetic resonance (MR) images from a patient classified as stable disease who nevertheless demonstrated substantial clinical improvement and is alive more than 5 years after treatment. These images depict two of the 11 hepatic metastases seen on the complete MR imaging (MRI) exam. The axial single-photon emission computed tomography ¹¹¹In-pentetreotide image on the right demonstrates significant concentration of the radiolabeled octreopeptide in the two lesions seen on MRI (arrows). (B) Pre- and post-therapy axial computed tomography (CT) images from a patient classified with partial response at the level of the upper pole of the left kidney and demonstrate substantial reduction in the size of multiple large hepatic metastases (t). Black arrow indicates uptake in a hepatic metastasis that is not seen on CT (S indicates spleen and K indicates upper pole of the left kidney on the pentetreotide image). This patient displayed dramatic clinical improvement as well.