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 (ots/PRNewswire) -

ASCO Abstract Number: 3506

- 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

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's leading 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 Università 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-naïve 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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