4991 - Relation between objective tumor shrinkage and progression-free survival (PFS) in the NETTER-1 population

Background

NETTER-1 demonstrated that Radioligand Therapy (RLT) with LUTATHERA^® significantly prolongs PFS in progressive midgut neuroendocrine tumor patients compared to 60 mg octreotide (Oct). In oncology, treatment efficacy has often been associated with early reduction of tumor size. As RLT differs from traditional treatments, we sought to verify whether objective tumor shrinkage predicts duration of PFS by assessing the relations between changes in lesion size and treatment efficacy, evaluated by PFS among NETTER-1 patients.

Methods

Post-hoc analyses were performed on the NETTER-1 population on local tumor imaging assessments on the full analyses set (n = 231) with data cut-off date on June 30^th, 2016. The best response (change from baseline in sum of target lesion diameters) during 3 intervals after treatment onset was used as a covariate in a Cox regression, thus differentiating whether the time corresponds to an event or a censoring. One interval corresponded to 150 days, i.e. a month prior to 4^th injection; 180 days matched the 4^th injection and the last interval was set to no limit.

Results

For patients treated with Oct, Cox regression showed a HR of 0.914 [95% CI: 0.860 – 0.971], p = 0.0034. This suggests that the risk of disease progression decreases by 9% for each incremental percentage of shrinkage. Among the patients treated with Lu, Cox regression showed a HR of 1.006 [0.982 – 1.03] p = 0.6236, suggesting that LUTATHERA^® prolonged PFS even when tumor objective response was undetected during treatment cycles. As a sensitivity, a 180-day-limit and no-limit (i.e. using the best response up to time of censoring/event) were also applied. With the 180-day-limit, HRs were 0.952 [0.904 - 1.003], p = 0.0652 and 1.013 [0.991-1.037], p = 0.2523 for Oct and Lu, respectively; similarly the no-limit, HRs were 0.952 [0.922, 0.982] p = 0.0023 and 1 [0.984, 1.017] p = 0.9713.

Conclusions

Durable response of LUTATHERA^® treatment goes beyond objective tumor shrinkage. This study conveys crucial information on the patient’s management with respect to LUTATHERA^®: treatment benefit of 4 cycles should not be assessed only by objective tumor shrinkage.

Clinical trial identification

NETTER-1: NCT01578239.

Editorial acknowledgement

Legal entity responsible for the study

Advanced Accelerator Applications.

Funding

Advanced Accelerator Applications.

Disclosure

M.E. Pavel: Advisory / Consultancy: Novartis. P. Broberg: Full / Part-time employment: Advanced Accelerator Applications. M. Caplin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Advanced Accelerator Applications. P. Ruszniewski: Speaker Bureau / Expert testimony: Advanced Accelerator Applications. P. Santoro: Full / Part-time employment: Advanced Accelerator Applications. L. Ravasi: Full / Part-time employment: Advanced Accelerator Applications. All other authors have declared no conflicts of interest.