Regression of advanced neuroendocrine tumors among patients receiving placebo
- Vito Amoroso1,*⇑,
- Giorgio Maria Agazzi2,*,
- Elisa Roca1,
- Nicola Fazio3,
- Alessandra Mosca4,
- Marco Ravanelli2,
- Francesca Spada3,
- Roberto Maroldi2 and
- Alfredo Berruti1
- 1Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology Unit, University of Brescia at ASST Spedali Civili, Brescia, Italy
- 2Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Radiology Unit, University of Brescia at ASST Spedali Civili, Brescia, Italy
- 3Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy
- 4Medical Oncology Unit, Maggiore della Carità University Hospital, University of Eastern Piedmont, Novara, Italy
- (Correspondence should be addressed to V Amoroso; email: vitoamoroso{at}alice.it)
Dear Editor,
The management of advanced well-differentiated or moderately differentiated neuroendocrine tumors (NETs) is challenging. These tumors, in fact, have a heterogeneous clinical behavior, many of them having an indolent disease course and some of them depicting an aggressive pattern. Few NETs may even undergo spontaneous remission, but this phenomenon has never been quantified and characterized. In this study, we performed a literature-based meta-analysis of all prospective randomized trials in which an active experimental treatment was compared with a placebo control arm and estimated the pooled rate of tumor shrinkage in placebo-treated patients. Our analysis clearly showed that a subset of NET patients attained a tumor shrinkage greater than 10% from baseline upon placebo, and this proportion was similar across the examined studies.
In the last few years, six randomized placebo-controlled trials have demonstrated that molecularly targeted therapies, such as somatostatin analogs (SSA) (Rinke et al. 2009, Caplin et al. 2014), everolimus (Pavel et al. 2011, Yao et al. 2011, 2016) and sunitinib (Raymond et al. 2011), are efficacious in prolonging progression-free survival among patients with gastroenteropancreatic (GEP) or pulmonary NETs. Two of these agents have also shown a marginal effect on overall survival (Raymond et al. 2011, Yao et al. 2011).
A true placebo was the selected control arm in five of these trials, whereas the control arm consisted of placebo plus an SSA in one trial enrolling patients with carcinoid syndrome-related NETs (Pavel et al. 2011).
The antitumor activity of novel molecularly targeted agents is commonly depicted by the waterfall plots, which report the percent change from baseline in size of target lesions on an individual basis. These graphics reveal that the patient subset with stable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) …
