Le Lézard
Classified in: Health, Science and technology
Subjects: Photo/Multimedia, Conference, Product/Service, Trade Show

Puma Biotechnology Presents Interim Results of Phase II CONTROL Trial of Neratinib in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the 2019 SABCS


Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, will present updated interim results from a Phase II clinical trial of Puma's drug neratinib at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The presentation entitled, "Effect of prophylaxis or neratinib dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2-positive early-stage breast cancer: Phase II CONTROL trial," will be displayed at a poster session on December 13 at 5:00 p.m. CST. A full copy of the poster is available on the Puma Biotechnology website.

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed in the United States as NERLYNX® (neratinib) tablets.

The main adverse event seen to date in clinical trials of neratinib is diarrhea and, more specifically, grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, prophylactic use of anti-diarrheal medications was not mandatory. In the trial, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The median cumulative duration of grade 3 diarrhea in the ExteNET trial was 5 days and 16.8% of patients who received neratinib in the ExteNET trial discontinued the drug due to diarrhea.

The CONTROL trial is an international, open-label, Phase II study investigating the use of antidiarrheal prophylaxis or dose escalation in the reduction of neratinib-associated diarrhea that has a primary endpoint of the incidence of grade 3 diarrhea.

In the CONTROL trial, patients with HER2-positive early stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. The trial initially tested high dose loperamide prophylaxis given for the first 2 cycles (56 days) of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed thereafter). The CONTROL trial was then expanded to include four additional cohorts. One cohort received the combination of loperamide and budesonide, the second cohort received the combination of loperamide plus colestipol, the third cohort received colestipol plus loperamide as needed and the fourth cohort did not use any antidiarrheal drugs as mandatory prophylaxis but instead used a dose escalation during the first month of neratinib treatment. Budesonide is a locally acting corticosteroid that Puma believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea and colestipol is a bile acid sequestrant that Puma believes targets potential bile acid malabsorption that could result from such inflammation. The dose escalation involved treating with neratinib at 120 mg per day for the first week, 160 mg per week for the second week and 240 mg per week starting at week 3 and until the end of treatment.

The interim analysis of the CONTROL trial presented in the poster included a total of 137 patients who received neratinib plus loperamide prophylaxis, 64 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle, 136 patients who received neratinib plus loperamide prophylaxis for 1 cycle and colestipol for 1 cycle, 104 patients who received colestipol for 1 cycle and loperamide as needed and 60 patients who received the dose escalation regimen of neratinib.

The results of the trial showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 31% and that for the 137 patients in this cohort, 20% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 64 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 28% and that for the 64 patients in this cohort, 11% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2.5 days.

For the 136 patients who received the combination of loperamide plus colestipol, the results of the trial showed that the incidence of grade 3 diarrhea was 21% and that for the 136 patients in this cohort, 4% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3.5 days.

For the 104 patients who received colestipol and loperamide as needed, the results of the trial showed that the incidence of grade 3 diarrhea was 34% and that for the 104 patients in this cohort, 8% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 60 patients who received no antidiarrheal drugs as mandatory prophylaxis and dose escalation of neratinib in the first month, the results of the trial showed that the incidence of grade 3 diarrhea was 15% and that for the 60 patients in this cohort, 3% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2 days.

Further information is provided in Table 1 below:

Table 1: Incidence of Treatment-Emergent Diarrhea

 

 

 

 

 

 

Neratinib dose

 

 

Budesonide +

 

Colestipol +

 

Colestipol +

 

escalation +

Loperamide

 

loperamide

 

loperamide

loperamide prn

 

loperamide prn

(n=137)

 

(n=64)

 

(n=136)

 

(n=104)

 

(n=60)

 

Treatment-emergent diarrhea incidence, n (%)

No diarrhea

28 (20)

 

9 (14)

 

23 (17)

 

5 (5)

 

2 (3)

Grade 1

33 (24)

 

16 (25)

 

38 (28)

 

33 (32)

 

24 (40)

Grade 2

34 (25)

 

21 (33)

 

47 (35)

 

31 (30)

 

25 (42)

Grade 3

42 (31)

 

18 (28)

 

28 (21)

 

35 (34)

 

9 (15)

Grade 4

0

 

0

 

0

 

0

 

0

 

 

 

 

 

 

 

 

 

Diarrhea leading to discontinuation

28 (20.4)

 

7 (10.9)

 

5 (3.7)

 

8 (7.7)

 

2 (3.3)

 

 

 

 

 

 

 

 

 

Hospitalization (due to diarrhea)

2 (1.5)

 

0

 

0

 

0

 

0

 

 

 

 

 

 

 

 

 

Discontinuation of study (any cause)

61 (44.5)

 

13 (20.3)

 

39 (28.7)

 

29 (27.9)

 

12 (20.0)

Note:

Each patient was counted only once in the highest grade category.

No Grade 4 events reported in the CONTROL study.

Carlos H. Barcenas, MD, MS, Associate Professor in the Department of Breast Medical Oncology of The University of Texas MD Anderson Cancer Center, said, "We are pleased to see the maturation of the data supporting observations of a reduction in incidence, severity and duration of neratinib-associated diarrhea with loperamide prophylaxis, loperamide plus budesonide prophylaxis or the loperamide plus colestipol prophylaxis. Along with the continued reduction in the incidence and severity of grade 3 diarrhea with neratinib, diarrhea appears to be early onset, acute, self-limiting and manageable. Not only does the addition of budesonide or colestipol to loperamide prophylaxis appear to greatly improve the tolerability of neratinib, the dose escalation regimen appears as another promising option since there is no mandatory prophylaxis."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to note that the dose-escalation cohort of our CONTROL trial continues to show a marked improvement in the incidence of grade 3 diarrhea and related discontinuation of therapy. We remain committed to improving the tolerability of neratinib in early stage breast cancer patients."

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (? 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS:

Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licenses the global development and commercialization rights to PB272 (neratinib, oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was approved by the U.S. Food and Drug Administration in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. NERLYNX was granted marketing authorization by the European Commission in August 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX is a registered trademark of Puma Biotechnology, Inc.

Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.


These press releases may also interest you

at 04:35
The global prescription lens market size is expected to reach USD 51.4 billion by 2027, expanding at a CAGR of 4.5%, according to a report conducted by Grand View Research, Inc. Uncorrected refractive error cases are majorly contributing in the...

at 04:09
We are advised by Sino Medical Sciences Technology Inc. (SINOMED) that journalists and other readers should disregard the news release, SINOMED® Completes Last Patient Follow-Up of the PIONEER-III Pivotal US and Japanese Trial of the BuMA Supreme®...

at 04:05
Mission Therapeutics ("Mission"), a drug discovery and development company focused on selectively inhibiting deubiquitylating enzymes (DUBs), today announced that it has raised $15m (£12m) in equity investment. The round was led by existing investor...

at 04:00
HOYA Corporation (TSE:7741, "HOYA") and Hitachi, Ltd. (TSE:6501, "Hitachi") today announced a five year contract regarding Endoscopic Ultrasound Systems [EUS] by which, i) the parties will strengthen technical collaboration, and ii) Hitachi will...

at 03:00
Morneau Shepell, a leading provider of total wellbeing, mental health and digital mental health services, today released its monthly Mental Health Indextm report. The June report marked the third consecutive month with a negative mental health score....

at 03:00
Rigaku Analytical Devices, the market leader in handheld 1064nm Raman technology, will present its solution for raw material identification during a webinar hosted by the Thai Industrial Pharmacist Association (TIPA) on July 16, 2020 at 9:30am ICT /...



News published on 13 december 2019 at 18:05 and distributed by: