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.

   All Merck Press Releases are distributed by e-mail at the same time they

become available on the Merck Website. Please go to:

http://www.merckgroup.com/subscribe to register online, change your selection

or discontinue this service.

   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