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Kisser, A.

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Baumann, M.

Grössmann, N.

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Fischer, S.

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Wolf, S.

Wild, C.

Horizon Scanning in Oncology    
 
Ergänzende Informationen zu den Arzneistoffen für Priorisierung XXIX – HSS Onkologie Seite 1 von 5 
 
 
 
 
 
Horizon Scanning in Oncology 
29
th
 Prioritization –  4 th quarter 2016 
 
General Information, efficacy and safety 
data 
 
 
 
 
 
 
Nicole Grössmann 
Sarah Wolf 
Claudia Wild 
 
 
 
Please note: 
Within this document you find general information about the drug of interest and the indication it is 
intended to be used for. Further we have included full text publications and conference abstracts of 
phase III trials, assessing the safety and efficacy of the drugs of interest. 
At the very end of each chapter we have provided a table containing the prioritization criteria and a 
drop-down field to apply the provided criteria. 
 
 
 
 
Ergänzende Informationen zu den Arzneistoffen für Priorisierung XXIX – HSS Onkologie Seite 2 von 5 
 
Ergänzende Informationen zu den Arzneistoffen für Priorisierung XXIX – HSS Onkologie Seite 3 von 5 
  
1 Breast cancer 
1.1 Neratinib after trastuzumab-based adjuvant therapy in patients 
with HER2-positive breast cancer 
Overview 
Drug Description 
tyrosine-kinase inhibitor that blocks signal transduction through three 
epidermal growth factor receptors (erbB1, erbB2/HER2, erbB4)  
Patient Indication 
Neratinib after trastuzumab-based adjuvant therapy in patients with early-
stage HER2-positive breast cancer 
Incidence in 
Austria 
5,594 newly diagnosed per year (2012), 40.3/100,000/year 
Ongoing Phase III NCT00878709 – until November 2020 
Approval 
status for 
this 
indication 
EMA - 
FDA - 
Approval 
status for 
other 
indications 
EMA - 
FDA - 
Costs - 
 
 
Phase III results  
Lancet (2016), Issue 17: 367–77 (Chan et al.) “Neratinib after trastuzumab-based adjuvant therapy in 
patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, 
placebo-controlled, phase 3 trial” 
 
Background  
Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in 
patients with HER2-positive metastatic breast cancer. We aimed to investigate the effi cacy and safety 
of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-
positive breast cancer. 
 
Methods  
We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in 
Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 
years, or ≥20 years in Japan) had stage 1–3 HER2-positive breast cancer and had completed 
neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria 
were amended on Feb 25, 2010, to include patients with stage 2–3 HER2-positive breast cancer who 
had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to 
receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was 
generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive 
[oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and 
progesterone receptor-negative]), nodal status (0, 1–3, or ≥4), and trastuzumab adjuvant regimen 
(sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice 
and web-response system. Patients, investigators, and trial sponsors were masked to treatment 
Ergänzende Informationen zu den Arzneistoffen für Priorisierung XXIX – HSS Onkologie Seite 4 von 5 
allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, 
at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with 
ClinicalTrials.gov, number NCT00878709. 
 
Results  
Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib 
(n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20–25) in the neratinib 
group and 24 months (22–25) in the placebo group. At 2 year follow-up, 70 invasive disease-free 
survival events had occurred in patients in the neratinib group versus 109 events in those in the 
placebo group (stratified hazard ratio 0·67, 95% CI 0·50–0·91; p=0·0091). The 2-year invasive 
disease-free survival rate was 93·9% (95% CI 92·4–95·2) in the neratinib group and 91·6% (90·0–
93·0) in the placebo group. The most common grade 3–4 adverse events in patients in the neratinib 
group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [<1%] vs grade 3, n=23 [2%] in the 
placebo group), vomiting (grade 3, n=47 [3%] vs n=5 [<1%]), and nausea (grade 3, n=26 [2%] vs n=2 
[<1%]). QT prolongation occurred in 49 (3%) patients given neratinib and 93 (7%) patients given 
placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 (1%) and 15 (1%) patients, 
respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 
(6%) patients in the placebo group. Seven (<1%) deaths (four patients in the neratinib group and three 
patients in the placebo group) unrelated to disease progression occurred after study drug 
discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary 
brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain 
haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were 
attributed to study treatment in either group. 
 
Conclusion 
Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after 
chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer. 
Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained. 
 
1.2 Ribociclib as First-Line Therapy for HR-Positive, Advanced 
Breast Cancer 
Overview 
Drug Description orally bioavailable, selective inhibitor of CDK4/6 
Patient Indication 
Ribociclib for the first-line treatment of postmenopausal women with HR 
positive and HER3-negative recurrent or metastatic breast cancer  
Incidence in 
Austria 
5,594 newly diagnosed per year (2012), 40.3/100,000/year 
Ongoing Phase III NCT01958021 – until August 2019 
Approval 
status for 
this 
indication 
EMA - 
FDA - 
Approval 
status for 
other 
indications 
EMA - 
FDA - 
Costs - 
 
 
Ergänzende Informationen zu den Arzneistoffen für Priorisierung XXIX – HSS Onkologie Seite 5 von 5 
Phase III results  
NEJM (2016), 375:1738-1748 (Hortobagyi et al.) “Ribociclib as First-Line Therapy for HR-Positive, 
Advanced Breast Cancer” 
 
Background 
The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay 
resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) 
and negative for human epidermal growth factor receptor 2 (HER2). 
 
Methods 
In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the 
selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 
postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who 
had not received previous systemic therapy for advanced disease. We randomly assigned the patients 
to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 
mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-
free survival. Secondary end points included overall survival, overall response rate, and safety. A 
preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease 
progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with 
P<1.29×10−5. 
 
Results 
The duration of progression-free survival was significantly longer in the ribociclib group than in the 
placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10−6 for superiority). The median 
duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% 
(95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in 
the placebo group. In patients with measurable disease at baseline, the overall response rate was 
52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in 
more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% 
in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of 
adverse events were 7.5% and 2.1%, respectively. 
 
Conclusion 
Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast 
cancer, the duration of progression-free survival was significantly longer among those receiving 
ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of 
myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov 
number, NCT01958021). 
 


HASH(0x558738ee1388)

Emprechtinger, R.

Erdos, J.

Piso, B.

HASH(0x558738dc8b48)

Stanak, M.

HASH(0x558738c72eb8)

Tüchler, H.

HASH(0x558738dac8f8)

HASH(0x558738f4a620)

Mantsch, S.

Petersen, P.

Gesamtsumme: 12,1 Mio bezahlt in 6.388 Einzelhonoraren (beinhaltet Mehrfachhonorare an Meinungsbildner) 
* PHARMIG-Mitgliedsunternehmen   © LBI-HTA 2016; Stand: Juli 2016; Detailnformationen auf www.hta.lbg.ac.at; Grak: mmp, www.multimediaproduktionen.at
Transparenz bei Pharmageldern
Zahlungen der Pharmarmen 2015 an ÄrztInnen und medizinische Institutionen in Österreich*
1. Zahlungen der Pharmafirmen - gesamt
Gesamtsumme: 104,1 Mio.€
2. Zahlungen für klinische Studien und Anwendungsbeobachtungen – TOP 10
3. Zahlungen an ÄrztInnen und Institutionen – TOP 10 (Firmen mit höchsten finanziellen Zuwendungen)
4. Zahlungen an ÄrztInnen
2,4 2,444,14,75 1,9
Valneva: 2,8 Mio.€
Novo Nordisk: 2,2 Mio.€Roche: 2,7 Mio.€
Bayer: 2,5 Mio.€
Amgen: 2,1 Mio.€ Abb Vie: 1,3 Mio.€
MSD: 1,2 Mio.€
Boehringer Ingelheim: 1 Mio.€
REST: 7,2 Mio.€
Novartis: 4 Mio.€Pfizer: 26,7 Mio.€
in %
49,5% 7,4 5,2
Gesamtsumme: 54 Mio.€
13%
Pfizer
Astra Zeneca
Novartis
Boehringer Ingelheim
Bayer
MSD Takeda REST
AbbVie Amgen
4,3 3,5 2,8 2,7 2,6 2,4 2,3 2,1 1,9 1,8
3,7
1,8 0,9
1,9
1,3
1,5 1,5 1,3
1,3
0,9
0,6 1,7 0,8 1,3 0,9 0,8 0,8 0,6 0,91,9
in Mio.€
Roche
Gesamtsumme: 22,4 Mio.€
Gesamtsumme (ÄrztInnen + Institutionen) Anteil ÄrztInnen Anteil Institutionen
Gesamtsumme Top10: 26,5 Mio.€
23,6 
Gesamtsumme an ÄrztInnen und Institutionen: 50,1 Mio.€
12,2  Mio.€
22,4 Mio.€ 18,6 Mio.€ 3,8 Mio.€
9,1 Mio.€
Besuch von Veranstaltungen  (41%)Honorare (54% )
Zahlungen an ÄrztInnen gesamt (100%) Zahlungen an ÄrztInnen aggregiert (83%) Zahlungen an ÄrztInnen individuell (17%)  
4.1. Offenlegungsbereitschaft von ÄrztInnen: individuell (namentlich) oengelegte vs. aggregiert (nicht namentlich) oengelegte Zahlungen
4.2. Beratungs- und Dienstleistungshonorare für ÄrztInnen: TOP 10 Durchschnitthonorare
Auslagen (5%)
1,1
Orion
€ 3.845
Vertex 
€ 3.800 
Lundbeck 
€ 3.645
Ipsen
€ 3.268
Eli Lilly 
€ 3.144 
CSL Behring
€ 3.028
Novo Nordisk
€ 3.014
Eisai
€ 2.901
Pfizer 
€ 2.685
Biogen 
€ 2.640
52%
22%
26%
54 Mio.€
22,4 Mio.€
27,7 Mio.€
für klinische Studien 
und Anwendungsbeobachtungen
an ÄrztInnen 
an medizinische Institutionen
Gesamt
104,1
Mio.€


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