Creating a specialized therapy center for novel radiolabelled agent

Neuroendocrine tumors are rare tumors of mostly GI tract (60-70%, including pancreas, colon, small bowel) and lung (20-30%), incidence 2/100,000, 93% cure rate for early stage, but only 19% survival at 5 years for metastatic tumors. They can lower quality of life through carcinoid syndrome-flushing, pain, fevers, diarrhea, niacin deficit. Findings from the phase III NETTER-1 trial led to the January 2018 FDA approval of Lutathera (lutetium Lu 177 dotatate) for the treatment of patients with somatostatin receptor–positive gastroenteropancreatic tumors (GEP-NETs). 

In NETTER-1, patients with midgut NETs who progressed on 30 mg of octreotide were randomized to Lutathera (n = 116) or high-dose octreotide (n = 113). Patients received 4 doses of Lutathera at 7.4 GBq every 8 weeks in combination with 30 mg of octreotide. The control arm received 60 mg of octreotide LAR every 4 weeks. In the study, there was a 79% reduction in the risk of progression or death with Lutathera compared with octreotide. The median progression-free survival (PFS) had not been reached in the Lutathera arm compared with 8.5 months in the high-dose octreotide arm (HR, 0.21; 95% CI, 0.13-0.32; P <.0001).  The overall response rate with Lutathera was 13% versus 4% with octreotide (P <.0148). At the interim analysis of overall survival (OS) there was a 48% reduction in the risk of death seen with Lutathera versus octreotide (HR, 0.52; 95% CI, 0.32-0.84).

Figure 1: Kaplan-Meier Curves for Progression-Free Survival in NETTER-1

The European Medicines Agency approved Lutathera in September 2017, and the FDA approved it at the end of January not only for midgut tumors, but also in NETs of the stomach, pancreas, colon and rectum.

The standard regimen consists of 200 mCi of lutetium Lu 177 dotatate once every 8 weeks x 4 treatments over 8 months. The drug is often given combined with a somatostatin analog, either a long-acting octreotide or lanreotide, especially in patients with carcinoid syndrome. It requires concomitant administration of aminoacid intravenous solution 30 minutes prior and at least 3 hours after therapy as well as special room shielding to prevent radioactive contamination.

One of the proposed areas for administration is the Clinical Research Unit, part of the 7th hospital floor used for clinical trial patient therapy. There is potentially one room which can accommodate one therapy patient (perhaps 2) one day a week (Friday), the other days the unit works at capacity and there would be very high potential for inducing errors either into the lutathera therapy or into the trial protocol ones. The challenges at this time are as follows:

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1. It is not clear how many patients will require this therapy immediately, vs. over the long term once the backlog of patients resolves.
2. The cost and logistics of refurbishing the room during normal operating conditions for the Research Unit.
3. The costs associated with refurbishing the room, additional staffing costs vs. reimbursement rates which are currently not yet clear.
4. Alternative solutions within the hospital where the radioactive shielding is already available were not clearly evaluated and rejected-at least not to my knowledge.
5. This therapy needs to be offered in the specialized higher volume centers such as ours, however, there was never any discussion or team preparation for this therapy from the CMO level.