1103P - 177Lu-DOTATATE efficacy and safety in functioning neuroendocrine tumors: A joint analysis of phase II prospective clinical trials

Background

Neuroendocrine tumors (NETs) are rare malignancies with different prognosis. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of ¹⁷⁷Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome.

Methods

A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed.

Results

Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, one (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2-63.2) median PFS was 33.0 months (95%CI: 27.1-48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8 months (95%CI: 76.1-94.1). Syndromic responders showed better survival than non responders, with a mOS of 93.9 (95%CI: 92.2-98.0) vs 40.0 months (95%CI: 6.6-73.4), respectively. Median time to syndrome response was 5.0 months (95% CI 4.0-6.5). Time to best tumor response was 7.3 months (95%CI: 5.8-7.9). Patients who underwent previous primary tumor surgery showed a benefit in terms of both mPFS and mOS, with a mPFS of 39.2 months (95%CI 28.3-54.1) compared to 24.9 months (13.8-39.5) for those who did not undergo surgery (P-value = .027). All patients with insulinoma showed a normalization of blood glucose levels and were able to suspend supportive glucose therapy.233 adverse events were recorded. Grade 1-2 haematological toxicity was the most frequent.

Conclusions

¹⁷⁷Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS.

Clinical trial identification

LUNET(NCT01740427) and LUTHREE (NCT01942135).

Editorial acknowledgement

Legal entity responsible for the study

IRST IRCCS.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.