Merck Announces New Retrospective Analysis Shows Significant Clinical Benefit in Overall Survival for Metastatic Colorectal Cancer Patients with RAS W
PR56758
Merck Announces New Retrospective Analysis Shows Significant Clinical Benefit in Overall Survival for Metastatic Colorectal Cancer Patients with RAS Wild-Type Tumors Receiving Erbitux plus FOLFIRI
DARMSTADT, Germany, May 15/PRN=KYODO JBN/--
- In a retrospective analysis of the Phase III CRYSTAL* study, which assessed
RAS tumor status, significant clinical benefit was observed in mCRC patients
with RAS wild-type tumors receiving Erbitux plus FOLFIRI, compared with FOLFIRI
alone
- No benefit was observed for patients with RAS mutations receiving Erbitux
plus FOLFIRI for the treatment of mCRC, compared with FOLFIRI alone, which is
in line with the EU label and recent scientific evidence
ASCO Abstract Number: 3506
Merck today announced new biomarker findings from a retrospective analysis
of the completed Phase III study CRYSTAL that compared Erbitux(R)(cetuximab)
plus FOLFIRI with FOLFIRI alone. The analysis involved a subgroup of patients
with KRAS wild-type (exon 2) metastatic colorectal cancer (mCRC). A significant
clinical improvement was observed in patients with RAS wild-type tumors when
Erbitux was added to FOLFIRI in firstline mCRC.[1] The new data will be
presented at the 2014 American Society of Clinical Oncology (ASCO) Annual
Meeting (May 30 - June 3) during the Gastrointestinal (Colorectal)session on
June 2, 2014, from 10:00 to 10:12 am. The results of this analysis reinforce
Merck's commitment to improve patient care, and underpins Merck'sleading role
in the highly innovative area of personalized cancer care.
In this new analysis, 430 (65% of 666 patients) patient tumor samples with
wild-type KRAS (exon 2) status were assessed for additional RAS mutations
(defined as mutations in exons 3 or 4 of KRAS and/or exons 2, 3 or 4 of NRAS).
Of these, 367 were RAS wild-type, while 63 presented a mutation. The analysis
shows a 27.7% increase in response rate (RR), a 3.0-month increase in median
progression-free survival (PFS), and an 8.2-month increase in median overall
survival (OS) in mCRC patients with RAS wild-type tumors (n=367) receiving
firstline Erbitux plus FOLFIRI, compared with patients receiving FOLFIRI alone
(RR: 66.3% vs. 38.6%, respectively; odds ratio: 3.11; 95% confidence interval
[CI]: 2.03-4.78; p<0.0001; PFS: median 11.4 months vs. 8.4 months,
respectively; hazard ratio [HR]: 0.56; 95% CI: 0.41-0.76; p=0.0002; OS: median
28.4 months vs. 20.2 months, respectively; HR: 0.69; 95% CI: 0.54-0.88;
p=0.0024).[1]
"The data from this analysis clearly demonstrate a clinical benefit from
treating RAS wild-type metastatic colorectal cancer patients with Erbitux plus
FOLFIRI, compared with FOLFIRI alone," said Dr. Steven Hildemann, Global Chief
Medical Officer and Head of Global Medical and Safety for Merck Serono. "This
CRYSTAL analysis contributes to our evolving understanding of this disease, and
confirms that RAS biomarker testing is essential for patient-centric care and a
truly personalized approach to metastatic colorectal cancer."
"The new analysis from the CRYSTAL study is in line with the results seen
from other studies with anti-epidermal growth factor receptor treatments in
metastatic colorectal cancer patients with RAS wild-type tumors," said
Professor Fortunato Ciardiello, Professor of Medical Oncology at the Seconda
Universita degli Studi di Napoli in Naples, Italy, and lead author of the
CRYSTAL RAS analysis. "Importantly, these results reinforce that RAS testing
should be conducted at the point of diagnosis in order to support physicians in
selecting the most appropriate firstline treatment for their mCRC patients."
In the patient group with either KRAS exon 2 mutations identified in the
initial KRAS analysis (n=397) or other RAS mutations (n=63) receiving Erbitux
plus FOLFIRI (n=246) no benefit was observed, compared with FOLFIRI alone
(n=214) (RR: 31.7% vs. 36.0%, respectively; odds ratio: 0.85; 95% CI:
0.58-1.25; p=0.40; PFS: median 7.4 months vs. 7.5 months, respectively; HR:
1.10; 95% CI: 0.85-1.42; p=0.47; OS: median 16.4 months vs. 17.7 months,
respectively; HR: 1.05; 95% CI: 0.86-1.28; p=0.64).[1] This subgroup analysis
confirms the findings of OPUS and other studies which have shown that patients
with RAS mutations do not benefit from anti-EGFR therapy.
Following an update to the Erbitux label that was approved by the European
Commission in December 2013, Erbitux is now indicated for the treatment of
patients with epidermal growth factor receptor-expressing RAS wild-type mCRC in
combination with irinotecan-based chemotherapy, in firstline in combination
with FOLFOX, or as a single agent in patients who have failed oxaliplatin- and
irinotecan-based therapy and who are intolerant to irinotecan. Erbitux is
contraindicated in combination with oxaliplatin-containing chemotherapy in
patients with mutant RAS mCRC or for whom RAS mCRC status is unknown.[2]
About CRYSTAL
CRYSTAL (Cetuximab combined with iRinotecan in first-line therapY for
metaSTatic colorectAL cancer) was a randomized, Phase III study involving 1,198
chemo-naive patients with EGFR-expressing mCRC in Stage IV, of whom 666 had
confirmed KRAS wild-type (exon 2) tumors. The study showed that
progression-free survival, overall survival time and response rate were
significantly better in patients with KRAS wild-type mCRC who received Erbitux
plus FOLFIRI, compared with FOLFIRI alone.[3]
About Colorectal Cancer
Colorectal cancer (CRC) is the second most common cancer worldwide, with an
estimated incidence of more than 1.36 million new cases annually.[4] An
estimated 694,000 deaths from CRC occur worldwide every year, accounting for
8.5% of all cancer deaths and making it the fourth most common cause of death
from cancer.[4] Almost 55% of CRC cases are diagnosed in developed regions of
the world, and incidence and mortality rates are substantially higher in men
than in women.[4]
*CRYSTAL: Cetuximab combined with iRinotecan in first-line therapY for
metaSTatic colorectAL cancer
References
1. Ciardiello F et al. Poster presentation at the 2014 American Society of
Clinical Oncology Annual Meeting, June 2, 2014. Abstract No:3506.
2. European Medicines Agency. Erbitux SmPC. Available at:
http://www.ema.europa.eu/ema. Last accessed May 2014.
3. Van Cutsem E, et al. J Clin Oncol 2011;29(15):2011-9.
4. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo
M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0, Cancer Incidence
and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon,
France: International Agency for Research on Cancer; 2013. Available at:
http://globocan.iarc.fr. Last accessed May 2014.
For more information on Erbitux in colorectal and head & neck cancer, please
visit: http://www.globalcancernews.com.
About Erbitux
Erbitux(R) is a first-in-class and highly active IgG1 monoclonal antibody
targeting the epidermal growth factor receptor (EGFR). As a monoclonal
antibody, the mode of action of Erbitux is distinct from standard non-selective
chemotherapy treatments in that it specifically targets and binds to the EGFR.
This binding inhibits the activation of the receptor and the subsequent
signal-transduction pathway, which results in reducing both the invasion of
normal tissues by tumor cells and the spread of tumors to new sites. It is also
believed to inhibit the ability of tumor cells to repair the damage caused by
chemotherapy and radiotherapy and to inhibit the formation of new blood vessels
inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash
that seems to be correlated with a good response to therapy. In approximately
5% of patients, hypersensitivity reactions may occur during treatment with
Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in over 90 countries for
the treatment of colorectal cancer and for the treatment of squamous cell
carcinoma of the head and neck (SCCHN).
Merck licensed the right to market Erbitux outside the US and Canada from
ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In
Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and
commercialize Erbitux. Merck has an ongoing commitment to the advancement of
oncology treatment and is currently investigating novel therapies in highly
targeted areas.
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Merck is a leading company for innovative and top-quality high-tech products
in the pharmaceutical and chemical sectors. With its four divisions Merck
Serono, Consumer Health, Performance Materials and Merck Millipore, Merck
generated total revenues of EUR 11.1 billion in 2013. Around 38,000 Merck
employees work in 66 countries to improve the quality of life for patients, to
further the success of our customers and to help meet global challenges. Merck
is the world's oldest pharmaceutical and chemical company - since 1668, the
company has stood for innovation, business success and responsible
entrepreneurship. Holding an approximately 70% interest, the founding family
remains the majority owner of the company to this day. Merck, Darmstadt,
Germany is holding the global rights to the Merck name and brand. The only
exceptions are Canada and the United States, where the company is known as EMD.
SOURCE: Merck KGaA
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