Next move might be PRRT in Germany

Dear friends,

Below is information about the PRRT treatment that I am going to attempt to do in Germany. While not yet approved in the US there are several places in the world doing it, Dr. Richard Baum in Germany being the one with the most experience. Several trials in the US currently should result in eventually approval here but it could be years. Following the
GA 68 scan I had during my Stanford Clinical Trial experience I began looking into this treatment. Last month my MRI showed a small amount of growth in a few of the tumors in my liver. There were no new tumors and many had not grown at all. The bone mets showed no growth. This may or may not mean disease progression. Normal time to tumor progression for those of us on Octreotide is a little over 2 years which is how long I have been on it. A few month ago I switched off of Octreotide to Lanreotide, a new drug just approved by the FDA here in the US but used elsewhere for years, that had performed a little better than Octreotide at slowing tumor growth. Unfortunately I have not felt well on it and have developed side effects similar to the carcinoid syndrome I have been lucky enough to not have had previously. Next week I will switch back to Octreotide injections. It continues to be so hard to know what to do with this disease. Should I stay on Lanreotide longer to see if it works and I feel better eventually? Do I feel bad from Lanreotide or for some other reason like disease progression?

I like Dr. Shankaran at Seattle Cancer Care Alliance (SCCA) and she seems to agree that switching back makes sense since it is unlikely that I developed the carcinoid syndrome now and the tumors have not yet grown to the degree that they would be causing more symptoms. We know this because of recent scans and labs that measure bio-markers for this type of cancer.

I am putting together a packet to mail to Germany with all my data and scans on a CD. I'm going to try to call them and mail it tomorrow. I'm excited about the Progression Free Survival (PFS) rates of PRRT written about below.

Good news for NET Cancer

·         October 04, 2015

·         By Tore Aasbu

·         Blog post by Bill Claxton.

Good news from Vienna, ECC 2015, the European Cancer Congress,
announced by Philippe Ruszniewski, MD, head of gastroenterology and pancreatology at Beaujon Hospital, in Clichy, France.

“Treatment with the novel peptide receptor radionuclide therapy (PRRT) Lutathera significantly increased progression-free survival (PFS) over octreotide LAR (Sandostatin) in patients with advanced midgut neuroendocrine tumors (NETs), according to findings from the phase III NETTER-1 trial presented at the 2015 European Cancer Congress.”
Medical abstract is here (www.europeancancercongress) and a press release is here (www.onclive.com).

 “This is the evidence we’ve been waiting for”

Not only does the NETTER1 trial result demonstrate that PRRT is the 2nd most effective treatment for mid-gut neuroendocrine tumor patients with SST receptors (after surgery)  it can potentially move PRRT to a 2nd-line therapy, to begin right after surgical removal of the primary (with SST analogs used for anti-proliferative maintenance thereafter).  These results will lead to changes in practice for functional mid-gut NETs, launch confirmatory studies for lung and hind-gut NET patients and provide a big boost to nuclear medicine programes worldwide!

 

 

Abstract title:  

LATE BREAKING ABSTRACT: 177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours: Results of the phase III NETTER-1 trial

J. Strosberg⁽¹⁾, E. Wolin⁽²⁾, B. Chasen⁽³⁾, M. Kulke⁽⁴⁾, D. Bushnell⁽⁵⁾, M. Caplin⁽⁶⁾, R.P. Baum⁽⁷⁾, E. Mittra⁽⁸⁾, T. Hobday⁽⁹⁾, A. Hendifar⁽¹⁰⁾, K. Oberg⁽¹¹⁾, M. Lopera Sierra⁽¹²⁾, P. Ruszniewski⁽¹³⁾, D. Kwekkeboom<sup>(14)

(1)</sup>H. Lee Moffitt Cancer Center & Research Institute, Medical Oncology and Hematology, Tampa, USA
⁽²⁾Markey Cancer Center - University of Kentucky, GI - Carcinoid and Neuroendocrine Cancer, Lexington, USA
⁽³⁾University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, USA
⁽⁴⁾Dana-Farber Cancer Institute, Neuroendocrine and Carcinoid Tumors, Boston, USA
⁽⁵⁾University of Iowa Carver College of Medicine, Division of Nuclear Medicine, Iowa City, USA
⁽⁶⁾Royal Free Hospital, Gastroenterology and Gastrointestinal Neuroendocrinology, London, United Kingdom
⁽⁷⁾Zentralklinik, Center for Neuroendocrine Tumors, Bad Berka, Germany
⁽⁸⁾Stanford University Medical Center, Radiology and Nuclear Medicine, Stanford, USA
⁽⁹⁾Mayo Clinic College of Medicine, Hematology and Oncology, Rochester, USA
⁽¹⁰⁾Cedars Sinai Medical Center, Gastrointestinal Oncology, Los Angeles, USA
⁽¹¹⁾Uppsala University Hospital, Endocrine Oncology, Uppsala, Sweden
⁽¹²⁾Advanced Accelerator Applications, Clinical Development, New York, USA
⁽¹³⁾Hopital Beaujon, Gastroenterology and Pancreatology, Clichy, France
⁽¹⁴⁾Erasmus Medical Center, Nuclear Medicine, Rotterdam, Netherlands

Background: Currently, there are limited therapeutic options for patients with advanced midgut neuroendocrine tumours (20–45% of NETs) progressing on first-line somatostatin analogue therapy. Since 2000, thousands of patients have been treated with ¹⁷⁷Lu-DOTA⁰-Tyr³-Octreotate (Lutathera^®) peptide receptor radionuclide therapy (PRRT) with promising results.

Material and Methods: NETTER-1 is the first Phase III multicentric, stratified, open, randomized, controlled trial evaluating Lutathera^® in patients with inoperable, progressive, somatostatin receptor positive midgut NETs. 230 patients with Grade 1–2 metastatic midgut NETs were randomized to receive Lutathera 7.4 GBq every 8 weeks (x4 administrations) with renal protection (amino acid solution infusion) versus Octreotide LAR 60mg every 4-weeks. The primary endpoint was PFS per RECIST 1.1 criteria, with objective tumour assessment performed by an independent reading center every 12 weeks until tumour progression. Secondary objectives included objective response rate, overall survival, TTP, safety, tolerability and health-related quality of life. An independent Data Safety Monitoring Board regularly assessed the safety outcome.

Results: Enrolment was completed in February 2015, with a target of 230 patients randomized (1:1) in 35 European and 15 sites in the United States. At the time of statistical analysis, the median PFS was not reached for Lutathera and was 8.4 months with 60mg Octreotide LAR [95% CI: 5.8–11.0 months], p<0.0001, with a hazard ratio of 0.21 [95% CI: 0.13–0.34]. The number of centrally confirmed disease progressions or deaths was 23 in the Lutathera group and 67 in the Octreotide LAR 60mg group. The safety profile observed in the study was consistent with the safety information generated in the Phase I-II clinical trial.

Conclusions: The Phase III NETTER-1 trial provides evidence for a clinically meaningful and statistically significant increase in PFS in patients with advanced midgut neuroendocrine tumours treated with Lutathera.

No conflict of interest.

Keywords:
177Lu-DOTATATE
Midgut Carcinoid Tumours
Peptide Receptor Radionuclide Therapy (PRRT)