-
The approval is based on data
showing Kadcyla cut the risk of disease recurring by half compared
to Herceptin in the adjuvant setting for specific patients with
HER2-positive early breast cancer
-
The application was approved in
just over 12 weeks under the US FDA's Real-Time Oncology Review
pilot programme
Basel, 06 May 2019 - Roche (SIX: RO, ROG; OTCQX:
RHHBY) today announced that the US Food and Drug Administration
(FDA) has approved Kadcyla® (trastuzumab emtansine) for adjuvant
(after surgery) treatment of people with HER2-positive early breast
cancer (eBC) who have residual invasive disease after neoadjuvant
(before surgery) taxane and Herceptin® (trastuzumab)-based
treatment.
"This approval is a significant treatment advance for HER2-positive
early breast cancer. By working closely with the FDA and
participating in the Real-Time Oncology Review pilot programme, we
are able to make Kadcyla available for people with residual
invasive disease after neoadjuvant therapy much sooner than
anticipated," said Sandra Horning, MD, Roche's Chief Medical
Officer and Head of Global Product Development. "With every step
forward in reducing the risk of disease recurrence, we come closer
to the goal of helping each person with early breast cancer have
the greatest opportunity for cure."
The goal in treating eBC is to provide people with the best chance
for a cure, which may involve treatment before and after surgery as
part of a comprehensive treatment approach.1,2 While
we come closer to this goal with each advance, many people still
have a disease recurrence in the long-term.3
Neoadjuvant treatment is given before surgery with the goal of
shrinking tumours and helping to improve surgical
outcomes.2 Adjuvant
treatment is given after surgery and aims to eliminate any
remaining cancer cells in the body to help reduce the risk of the
cancer returning.2
The FDA rapidly reviewed and approved the application under the
FDA's Real-Time Oncology Review (RTOR) and Assessment Aid pilot
programmes, leading to an approval in just over 12 weeks after
completing the submission. Kadcyla is the first Roche medicine
approved under the RTOR pilot programme, which is exploring a more
efficient review process to ensure safe and effective treatments
are available to patients as early as possible.4 For
this indication, Kadcyla was also granted Breakthrough Therapy
Designation, which is designed to expedite the development and
review of medicines intended to treat serious or life-threatening
diseases.5
This approval is based on results of the phase III KATHERINE study
showing Kadcyla significantly reduced the risk of invasive breast
cancer recurrence or death from any cause (invasive disease-free
survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001)
compared to Herceptin as an adjuvant treatment in people with
HER2-positive eBC who have residual invasive disease after
neoadjuvant taxane and Herceptin-based treatment.6 At
three years, 88.3% of people treated with Kadcyla did not have
their breast cancer return compared to 77.0% treated with
Herceptin, an absolute improvement of 11.3%.6 People
who have residual disease after neoadjuvant treatment have a worse
prognosis than those with no detectable disease.7,8
The most common Grade 3 or higher side effects (>2%) with
Kadcyla in the KATHERINE study were decreased platelet count and
high blood pressure. The most common side effects (>25%) with
Kadcyla were fatigue; nausea; increased blood levels of liver
enzymes; musculoskeletal pain; bleeding; decreased platelet count;
headache; numbness, tingling or pain in the hands or feet; and
joint pain.6,9
About the KATHERINE study10
KATHERINE is an international, multi-centre, two-arm, randomised,
open-label, phase III study evaluating the efficacy and safety of
Kadcyla versus Herceptin as an adjuvant therapy in people with
HER2-positive eBC who have pathological invasive residual disease
in the breast and/or axillary lymph nodes following neoadjuvant
therapy that included Herceptin and taxane-based chemotherapy. The
primary endpoint of the study is iDFS, which in this study is
defined as the time from randomisation free from invasive breast
cancer recurrence or death from any cause. Secondary endpoints
include iDFS including second primary non-breast cancer,
disease-free survival and overall survival.
KATHERINE
Study Results6 |
|
Kadcyla
n=743 |
Herceptin
n=743 |
Median follow-up |
40
months |
Invasive disease-free survival (iDFS) |
Risk reduction |
HR=0.50,
95% CI 0.39-0.64, p<0.0001 |
3-year iDFS |
88.3% |
77.0% |
11.3%
absolute improvement |
Adverse reactions (ARs) |
Grade >=3AR |
26% |
15% |
Most common Grade >=3 ARs (>2%) |
Thrombocytopenia (decreased platelet count) |
6% |
0.3% |
Hypertension (high blood pressure) |
2.0% |
1.2% |
About Kadcyla
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver
potent chemotherapy directly to HER2-positive cancer cells,
potentially limiting damage to healthy tissues.11,12 It
combines two anti-cancer properties joined together by a stable
linker: the HER2-targeting properties of trastuzumab (the active
ingredient in Herceptin) and the chemotherapy agent DM1.13 Kadcyla is
the only ADC approved as a single agent in 104 countries including
the US and EU for the treatment of people with HER2-positive
metastatic breast cancer who have previously received Herceptin and
taxane chemotherapy, separately or in combination. Roche licenses
technology for Kadcyla under an agreement with ImmunoGen,
Inc.
About Roche's medicines for HER2-positive breast
cancer
Roche has been leading research into the HER2 pathway for over 30
years and is committed to improving the health, quality of life and
survival of people with both early and advanced HER2-positive
disease. HER2-positive breast cancer is a particularly aggressive
form of the disease that affects approximately 15-20% of
patients.14 Roche has
developed three innovative medicines that have helped transform the
treatment of HER2-positive breast cancer: Herceptin (trastuzumab),
Perjeta® (pertuzumab) and Kadcyla (trastuzumab emtansine).
Eligibility for treatment with Roche's HER2-targeted medicines is
determined via a diagnostic test, which identifies people who will
likely benefit from these medicines at the onset of their
disease.
About Roche
Roche is a
global pioneer in pharmaceuticals and diagnostics focused on
advancing science to improve people's lives. The combined strengths
of pharmaceuticals and diagnostics under one roof have made Roche
the leader in personalised healthcare - a strategy that aims to fit
the right treatment to each patient in the best way
possible.
Roche is the world's largest biotech company, with truly
differentiated medicines in oncology, immunology, infectious
diseases, ophthalmology and diseases of the central nervous system.
Roche is also the world leader in in vitro diagnostics and
tissue-based cancer diagnostics, and a frontrunner in diabetes
management.
Founded in 1896, Roche continues to search for better ways to
prevent, diagnose and treat diseases and make a sustainable
contribution to society. The company also aims to
improve patient access to medical innovations by working with
all relevant stakeholders. Thirty medicines developed by Roche are
included in the World Health Organization Model Lists of Essential
Medicines, among them life-saving antibiotics, antimalarials and
cancer medicines. Moreover, for the tenth consecutive year, Roche
has been recognised as the most sustainable company in the
Pharmaceuticals Industry by the Dow Jones Sustainability Indices
(DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in
over 100 countries and in 2018 employed about 94,000 people
worldwide. In 2018, Roche invested CHF 11 billion in R&D and
posted sales of CHF 56.8 billion. Genentech, in the United
States, is a wholly owned member of the Roche Group. Roche is the
majority shareholder in Chugai Pharmaceutical, Japan. For more
information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by
law.
References
[1] Scharl A, et
al. Geburtshilfe Frauenheilkd. 2015;75(7):683-91.
[2] Johns Hopkins Medicine. Neoadjuvant and Adjuvant Chemotherapy.
[Internet; cited April 2019]. Available from:
http://www.hopkinsmedicine.org/breast_center/treatments_services/medical_oncology/neoadjuvant_adjuvant_chemotherapy.html.
[3] Slamon D, et al. BCIRG 006 trial. Presented at: SABCS; 2015 Dec
6-10; San Antonio, TX, USA. Abstract #S5-04.
[4] US Food and Drug Administration. Real-Time Oncology Review
Pilot Program. [Internet; cited April 2019]. Available from:
https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OCE/ucm612927.htm.
[5] US Food and Drug Administration. Breakthrough Therapy.
[Internet; cited April 2019]. Available from:
https://www.fda.gov/ForPatients/Approvals/Fast/ucm405397.htm.
[6] Minckwitz G, et al. N Engl J Med.
2018;DOI:10.1056/NEJMoa1814017.
[7] Cortazar P, et al. Lancet. 2014;384(9938):164-72.
[8] Gianni L, et al. Lancet. 2016;17(6):791-800.
[9] US Food and Drug Administration. Prescribing Information for
Kadcyla. [Internet; cited April 2019]. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125427lbl.pdf
[10] ClinicalTrials.gov. A Study of Trastuzumab Emtansine Versus
Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive
Breast Cancer Who Have Residual Tumor in the Breast or Axillary
Lymph Nodes Following Preoperative Therapy (KATHERINE). [Internet;
cited April 2019]. Available from:
https://clinicaltrials.gov/ct2/show/NCT01772472.
[11] Hurvitz SA, et al. J Clin Oncol. 2013;31(9):1157-63.
[12] Verma S, et al. N Engl J Med. 2012;367(19):1783-91.
[13] Junttila TT, et al. Breast Cancer Res Treat.
2011;128:347-56.
[14] Wolff AC, et al. J Clin Oncol. 2013;31(31):3997-4013.
Roche Group Media
Relations
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- Nicolas Dunant (Head)
- Patrick Barth
- Ulrike Engels-Lange
- Simone Oeschger
- Anja von Treskow
FDA approves Kadcyla (KATHERINE
study)