MSD's KEYTRUDA (pembrolizumab) Becomes the First Immunotherapy, When Used in Combination with Chemotherapy, to Be Recommended by NICE for Inclusion in the Cancer Drugs Fund for Untreated, Metastatic, Non-Squamous Non-Small Cell Lung Cancer
Eligible NHS Patients in England with Untreated, Metastatic, Non-Squamous, Non-Small Cell Lung Cancer Can Now Access Pembrolizumab Plus Pemetrexed and Platinum-Based Chemotherapy
Hoddesdon, November 22, 2018 - Today, MSD (tradename of Merck & Co., Inc., Kenilworth, N.J., USA (NYSE: MRK)) announced that the National Institute for Health and Care Excellence (NICE) has issued a final appraisal determination (FAD) that recommends inclusion of KEYTRUDA® (pembrolizumab) in the Cancer Drugs Fund (CDF) when used in combination with pemetrexed and platinum-based chemotherapy as an option for untreated, metastatic, non-squamous non-small-cell lung cancer (NSCLC) in adults whose tumours have no epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)-positive mutations. It is only recommended if:
- pembrolizumab is stopped at 2 years of uninterrupted treatment or earlier if disease progresses, and
- the company provides pembrolizumab according to the managed access agreement1
This decision makes pembrolizumab the first immunotherapy to be made available to NHS patients in England when used in combination with chemotherapy for the treatment of advanced NSCLC.
Paula Chadwick, Chief Executive, Roy Castle Lung Cancer Foundation, said, “We welcome this decision by NICE as it opens up access to immunotherapy to a group of lung cancer patients who were not previously eligible. It’s positive news, not just for those patients who may now benefit from pembrolizumab, but for the lung cancer community as this really is great progress. It clearly demonstrates the excellent work being carried out by researchers worldwide to expand the range of treatment options.”
Toby Talbot, Consultant Clinical Oncologist, Royal Cornwall Hospital, NHS, and KEYNOTE-189 investigator said: “This could be one of the biggest advances in the treatment of non-small cell lung cancer in recent years. The results are particularly impressive for patients with low PDL1 expression – these patients have not been able to access the benefits of immunotherapy without having conventional chemotherapy first. The availability of combination therapy is a huge leap forward in improving the prognosis of patients with non-squamous non-small cell lung cancer.”
Dr. Katy Clarke, Consultant Clinical Oncologist, The Leeds Teaching Hospitals said “This is incredibly exciting news for patients and physicians alike and another huge step forward for immunotherapies in the treatment of lung cancer. We have already seen how effective pembrolizumab has been when used on its own for the treatment of a subset of patients with advanced non-small cell lung cancer. Adding chemotherapy has opened up its benefits to more patients with untreated, non-squamous non-small cell lung cancer.”
Lung cancer is the third most common cancer in the UK, with more than 46,000 new cases diagnosed in 2015 in the UK. [i] It is the leading cause of cancer-related mortality in the UK and currently only 5% of lung cancer patients survive the condition for ten or more years in England and Wales. The survival rate has changed very little in the last 40 years from 3% to 5%.[ii] There are usually no signs or symptoms in the early stages of lung cancer and 72-76% of people are diagnosed at a late stage (stage III or IV) when the cancer has spread outside the lungs.[iii]
Vanessa Beattie, Chair, National Lung Cancer Forum for Nurses and Clinical Nurse Specialist, Aintree University Hospital, Liverpool said, “People with late stage lung cancer have very few treatment options available. Today’s NICE decision is fantastic news because many more patients with this specific type of lung cancer will be able to access treatment with immunotherapy. These treatments can have real benefits for patients”
Inclusion in the CDF shows that NICE considers pembrolizumab in combination with chemotherapy has potential to satisfy the criteria for routine use on the NHS for this group of NSCLC patients but needs more investigation, through data collection in the NHS, before making a final decision on routine commissioning. The CDF has been set up to allow NHS patients in England faster access to the most promising new cancer treatments.
Louise Houson, UK Managing Director, MSD said; “Lung Cancer continues to affect too many people in the UK and is a key disease area for MSD. We are delighted to see this reflected by NICE with today’s recommendation. We are committed to working closely with NHS England and NICE so that patients can continue to access pembrolizumab in combination with chemotherapy in the longer term.”
NICE based their recommendation on data from MSD’s KEYNOTE-189 clinical study, which demonstrated that pembrolizumab in combination with pemetrexed and platinum-based chemotherapy reduced the risk of death by 51% (HR=0.49 [95% CI: 0.38-0.64]; p<0.001) in patients with untreated, metastatic, non-squamous NSCLC compared to pemetrexed and platinum-based chemotherapy alone, as well as showing a reduction in the risk of disease progression or death of 48% (HR=0.52 [95% CI, 0.43-0.64]; p<0.001). Overall survival (OS) and progression-free survival (PFS) were primary endpoints of the KEYNOTE-189 study.[iv] The safety of pembrolizumab was consistent with what has been seen in previous trials among patients with metastatic NSCLC.
Notes to editors:
About Non-Small-Cell Lung Cancer
Non-small cell lung cancer (NSCLC) is a disease in which cancerous cells form in the tissues of the lung. NSCLC makes up 87% of all lung cancers in the UK. The three common types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.[v]
Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, pembrolizumab releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumour immune response.[vi]
For detailed information regarding pembrolizumab, please refer to the Summary of Product Characteristics, available online at https://www.medicines.org.uk/emc/medicine/30602
KEYNOTE-189 (ClinicalTrials.gov, NCT02578680, a randomised, double-blind, placebo-controlled, Phase 3 study, evaluated pembrolizumab in combination with pemetrexed and cisplatin or carboplatin, compared with pemetrexed and cisplatin or carboplatin alone, in 616 patients with metastatic non-squamous NSCLC, regardless of PD-L1 expression. Patients had no EGFR or ALK genomic tumour aberrations and had not previously received systemic therapy for advanced disease. The dual primary endpoints were overall survival (OS) and progression-free survival (PFS).
With a median follow-up of 10.5 months (range, 0.2-20.4), pembrolizumab in combination with pemetrexed and a platinum chemotherapy demonstrated superior improvements in OS, with a 51 percent reduction in the risk of death, compared with pemetrexed plus platinum chemotherapy alone (HR=0.49 [95% CI: 0.38-0.64]; p<0.001). In the study, 69.2 percent of patients were alive at 12 months in the pembrolizumab treatment group (95% CI, 64.1-73.8%), compared with 49.4 percent in the chemotherapy alone group (95% CI, 42.1-56.2%).There was also a significant improvement in PFS for pembrolizumab in combination with pemetrexed and platinum chemotherapy with a 48 percent reduction in the risk of disease progression or death compared with pemetrexed plus platinum chemotherapy alone (HR=0.52 [95% CI, 0.43-0.64]; p<0.001). The percentage of patients who were alive with no progression of disease at 12 months was 34.1 percent in the pembrolizumab combination group (95% CI, 28.8-39.5%), which was nearly double the percentage (17.3 percent) of the pemetrexed plus platinum chemotherapy group (95% CI, 12.0-23.5%).
The safety of pembrolizumab was consistent with what has been seen in previous trials among patients with metastatic NSCLC. Grade 3-5 treatment-related adverse events from any cause occurred in 67.2 percent of patients in the pembrolizumab plus pemetrexed and platinum chemotherapy group, and 65.8 percent in the pemetrexed and platinum chemotherapy alone arm. Treatment-related adverse events of any grade and from any cause with an incidence of 15 percent or more in the pembrolizumab group were nausea (55.6%), anaemia (46.2%), fatigue (40.7%), constipation (34.8%), diarrhoea (30.9%), decreased appetite (28.1%), neutropenia (27.2%), vomiting (24.2%), cough (21.5%), dyspnoea (21.1%), asthenia (20.5%), rash (20.2%), pyrexia (19.5%), oedema peripheral (19.3%), thrombocytopenia (18.0%), increased lacrimation (17.0%). The most common immune-mediated treatment-related adverse events of any grade in patients receiving pembrolizumab plus pemetrexed and platinum chemotherapy were hypothyroidism (6.7%), pneumonitis (4.4%), hyperthyroidism (4.0%), infusion reactions (2.5%), colitis (2.2%), severe skin toxicity (2.0%), nephritis (1.7%) and hepatitis (1.2%). There were three treatment-related deaths from pneumonitis in the pembrolizumab plus pemetrexed and platinum chemotherapy group.
The KEYNOTE-189 study was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA).
NICE stands for The National Institute for Health and Care Excellence. It is an independent organisation, set up by the Government in 1999. NICE decides which drugs and treatments are available on the NHS in England and Wales. The All Wales Medicines Strategy Group also makes some decisions for the NHS in Wales. Generally, they follow NICE decisions. Scotland and Northern Ireland have separate organisations to make decisions. Once NICE issues its guidance, NHS trusts must find the money to make those drugs or treatments available.
About the Cancer Drugs Fund
The Cancer Drugs Fund (CDF) was set up in April 2011 to allow NHS patients in England access to cancer drugs which are not routinely available on the NHS. In October 2015, the CDF was closed to new drugs and a full public consultation carried out to make the fund more sustainable. In July 2016, it re-opened following extensive reforms. The process for assessing cancer drugs that is used by the NICE now includes a decision about funding under the CDF.
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At MSD Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.
For more than a century, MSD, a leading global biopharmaceutical company, has been bringing forward medicines and vaccines for the world’s most challenging diseases. MSD is a trade name of Merck & Co., Inc., with headquarters in Kenilworth, N.J., U.S.A. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programmes and partnerships. Today, MSD continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world. For more information, visit www.msd-UK.com and connect with us on Twitter @MSDintheUK.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbour provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
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The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2016 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
[i] Cancer Research UK. (2018). Lung cancer statistics. [online] Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Zero [Accessed 25 October. 2018].
[ii] Cancer Research UK. (2018) Lung cancer survival statistics.[online] Available at http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/survival. [Accessed 25 October 2018].
[iii] Cancer Research UK. (2018). Lung cancer incidence statistics. [online] Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/incidence#ref-5 [Accessed 25 October 2018].
[iv] Ghandi, L.(2018). Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. New England Journal of Medicine, 378(22), pp.2078-2092.
[v] Cancer Research UK. Types of Lung Cancer. Available at: http://www.cancerresearchuk.org/about-cancer/type/lung-cancer/about/types-of-lung-cancer. [Accessed 25 October 2018]
[vi] Reck M, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8.
[vii] Cancerresearchuk.org. (2018). About NICE | General cancer information | Cancer Research UK. [online] Available at: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/access-to-treatment/nice/about [Accessed 7 Nov. 2018].
[viii] Cancerresearchuk.org. (2018). How NICE makes decisions | Cancer information | Cancer Research UK. [online] Available at: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/access-to-treatment/nice/decisions [Accessed 7 Nov. 2018].
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